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1
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Coelho DRA, da Luz RO, Basto ST, de Sousa CCT, da Silva HP, de Sousa Martins Fernandes E, Brito-Azevedo A. Prolonged Anhepatic State as a Bridge to Retransplantation: A Challenging Case of a 35-Year-Old Male Liver Transplant Patient with a Temporary Portacaval Shunt. AMERICAN JOURNAL OF CASE REPORTS 2023; 24:e941933. [PMID: 38150414 PMCID: PMC10763644 DOI: 10.12659/ajcr.941933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 11/24/2023] [Accepted: 11/03/2023] [Indexed: 12/29/2023]
Abstract
BACKGROUND Liver transplantation is a life-saving intervention for patients with a diagnosis of acute liver failure or end-stage liver disease. Despite advances in surgical techniques and immunosuppressive therapies, primary nonfunction remains a concern, often necessitating retransplantation. In these scenarios, the anhepatic state, achieved through total hepatectomy with a temporary portacaval shunt, serves as a bridge to retransplantation. However, the challenge lies in the uncertain survival period and several potential complications associated with this procedure. CASE REPORT We present a case of a 35-year-old male patient with autoimmune hepatitis who underwent liver transplantation from a deceased donor. Seven days later, he experienced acute liver failure, leading to an urgent listing for retransplantation. To prevent the intense systemic inflammatory response, the patient underwent a total hepatectomy with a temporary portacaval shunt while awaiting another graft and endured a 57-h anhepatic state. On day 17 following retransplantation, he had cerebral death due to a hemorrhagic stroke. CONCLUSIONS This case underscores one of the most prolonged periods of anhepatic state as a bridge to retransplantation, highlighting the complexities associated with this technique. The challenges include sepsis, hypotension, coagulopathy, metabolic acidosis, renal failure, electrolyte disturbances, hypoglycemia, and hypothermia. Vigilant monitoring and careful management are crucial to improve patient outcomes. Further research is needed to optimize the duration of the anhepatic state and minimize complications for liver transplantation recipients.
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Affiliation(s)
| | | | - Samanta Teixeira Basto
- Department of Gastrointestinal and Liver Transplant Surgery, Hospital Adventista Silvestre (HAS), Rio de Janeiro, RJ, Brazil
| | | | | | | | - Anderson Brito-Azevedo
- Department of Gastrointestinal and Liver Transplant Surgery, Hospital Adventista Silvestre (HAS), Rio de Janeiro, RJ, Brazil
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2
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Cooper KM, Colletta A, Moulton K, Ralto KM, Devuni D. Kidney disease in patients with chronic liver disease: Does sex matter? World J Clin Cases 2023; 11:3980-3992. [PMID: 37388789 PMCID: PMC10303604 DOI: 10.12998/wjcc.v11.i17.3980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/30/2023] [Accepted: 05/16/2023] [Indexed: 06/12/2023] Open
Abstract
Kidney disease in patients with liver disease is serious and increases mortality. Up to 50% of patients hospitalized experience an episode of acute kidney injury. In general, men with liver disease are thought to be at increased risk of kidney disease. However, this association should be considered with caution because most studies use creatinine-based inclusion criteria, which is negatively biased against women. In this review, we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.
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Affiliation(s)
- Katherine M Cooper
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Alessandro Colletta
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kristen Moulton
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kenneth M Ralto
- Department of Medicine, Division of Renal Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Deepika Devuni
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
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3
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Ortiz C, Klein S, Reul WH, Magdaleno F, Gröschl S, Dietrich P, Schierwagen R, Uschner FE, Torres S, Hieber C, Meier C, Kraus N, Tyc O, Brol M, Zeuzem S, Welsch C, Poglitsch M, Hellerbrand C, Alfonso-Prieto M, Mira F, Keller UAD, Tetzner A, Moore A, Walther T, Trebicka J. Neprilysin-dependent neuropeptide Y cleavage in the liver promotes fibrosis by blocking NPY-receptor 1. Cell Rep 2023; 42:112059. [PMID: 36729833 PMCID: PMC9989826 DOI: 10.1016/j.celrep.2023.112059] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 11/17/2022] [Accepted: 01/18/2023] [Indexed: 02/03/2023] Open
Abstract
Development of liver fibrosis is paralleled by contraction of hepatic stellate cells (HSCs), the main profibrotic hepatic cells. Yet, little is known about the interplay of neprilysin (NEP) and its substrate neuropeptide Y (NPY), a potent enhancer of contraction, in liver fibrosis. We demonstrate that HSCs are the source of NEP. Importantly, NPY originates majorly from the splanchnic region and is cleaved by NEP in order to terminate contraction. Interestingly, NEP deficiency (Nep-/-) showed less fibrosis but portal hypertension upon liver injury in two different fibrosis models in mice. We demonstrate the incremental benefit of Nep-/- in addition to AT1R blocker (ARB) or ACE inhibitors for fibrosis and portal hypertension. Finally, oral administration of Entresto, a combination of ARB and NEP inhibitor, decreased hepatic fibrosis and portal pressure in mice. These results provide a mechanistic rationale for translation of NEP-AT1R-blockade in human liver fibrosis and portal hypertension.
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Affiliation(s)
- Cristina Ortiz
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Sabine Klein
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany; Department of Internal Medicine B, University of Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany
| | - Winfried H Reul
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | - Stefanie Gröschl
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Peter Dietrich
- Institute of Biochemistry, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; Department of Internal Medicine 1, FAU Erlangen-Nuremberg and Universitätsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany
| | - Robert Schierwagen
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Frank E Uschner
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Sandra Torres
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Christoph Hieber
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Caroline Meier
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Nico Kraus
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Olaf Tyc
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Maximilian Brol
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Christoph Welsch
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | | | - Claus Hellerbrand
- Institute of Biochemistry, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Mercedes Alfonso-Prieto
- Institute for Neuroscience and Medicine INM-9 and Institute for Advanced Simulations IAS-5, Forschungszentrum Jülich, Jülich, Germany; Cécile and Oskar Vogt Institute for Brain Research, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Fabio Mira
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
| | - Ulrich Auf dem Keller
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
| | - Anja Tetzner
- Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland
| | - Andrew Moore
- Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland
| | - Thomas Walther
- Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland; Department of Pediatric Surgery, Centre for Fetal Medicine, Division of Women and Child Health, University of Leipzig, Leipzig, Germany; Department of Obstetrics, Centre for Fetal Medicine, Division of Women and Child Health, University of Leipzig, Leipzig, Germany
| | - Jonel Trebicka
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany; Institute of Clinical Research, Odense University Hospital, University of Southern Denmark, Odense, Denmark; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain; Institute for Bioengineering of Catalonia, Barcelona, Spain; Department of Internal Medicine B, University of Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
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4
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Rodrigues SG, Mendoza YP, Bosch J. Investigational drugs in early clinical development for portal hypertension. Expert Opin Investig Drugs 2022; 31:825-842. [PMID: 35758843 DOI: 10.1080/13543784.2022.2095259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Advanced chronic liver disease is considered a reversible condition after removal of the primary aetiological factor. This has led to a paradigm shift in which portal hypertension (PH) is a reversible complication of cirrhosis. The pharmacologic management of PH is centered on finding targets to modify the natural history of cirrhosis and PH. AREAS COVERED This paper offers an overview of the use of pharmacological strategies in early clinical development that modify PH. Papers included were selected from searching clinical trials sites and PubMed from the last 10 years. EXPERT OPINION A paradigm shift has generated a new concept of PH in cirrhosis as a reversible complication of a potentially curable disease. Decreasing portal pressure to prevent decompensation and further complications of cirrhosis that may lead liver transplantation or death is a goal. Therapeutic strategies also aspire achieve total or partial regression of fibrosis thus eliminating the need for treatment or screening of PH.
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Affiliation(s)
- Susana G Rodrigues
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.,Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
| | - Yuly P Mendoza
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.,Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland.,Graduate School for Health Sciences (GHS), University of Bern
| | - Jaime Bosch
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.,Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
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Abstract
Hepatorenal syndrome (HRS) is defined as a functional renal failure without major histologic changes in individuals with severe liver disease and it is associated with a high mortality rate. Renal hypoperfusion due to marked vasoconstriction as a result of complex circulatory dysfunction has been suggested to be the cornerstone of HRS. Splanchnic and peripheral arterial vasodilation and cirrhotic cardiomyopathy result in effective arterial hypovolemia and compensatory activation of vasoconstrictor mechanisms. The efficacy of current therapeutic strategies targeting this circulatory dysfunction is limited. Increasing evidence suggests a substantial role of systemic inflammation in HRS via either vascular or direct renal effects. Here we summarize the current understanding of HRS pathophysiology.
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Affiliation(s)
- Timea Csak
- Sandra Atlas Bass Center for Liver Diseases, Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
| | - David Bernstein
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, 400 Community Drive, Manhasset, NY 11030, USA
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Manrai M, Tilak TVSVGK, Dawra S, Srivastava S, Singh A. Current and emerging therapeutic strategies in pancreatic cancer: Challenges and opportunities. World J Gastroenterol 2021; 27:6572-6589. [PMID: 34754153 PMCID: PMC8554408 DOI: 10.3748/wjg.v27.i39.6572] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 05/09/2021] [Accepted: 08/16/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic carcinoma (PC) is one of the leading causes of cancer-related deaths worldwide. Despite early detection and advances in therapeutics, the prognosis remains dismal. The outcome and therapeutic approach are dependent on the stage of PC at the time of diagnosis. The standard of care is surgery, followed by adjuvant chemotherapy. The advent of newer drugs has changed the landscape of adjuvant therapy. Moreover, recent trials have highlighted the role of neoadjuvant therapy and chemoradiotherapy for resectable and borderline resectable PC. As we progress towards a better understanding of tumor biology, genetics, and microenvironment, novel therapeutic strategies and targeted agents are now on the horizon. We have described the current and emerging therapeutic strategies in PC.
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Affiliation(s)
- Manish Manrai
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, Maharashtra, India
| | - T V S V G K Tilak
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, Maharashtra, India
| | - Saurabh Dawra
- Department of Internal Medicine, Command Hospital, Pune 411040, Maharashtra, India
| | - Sharad Srivastava
- Department of Internal Medicine, Command Hospital, Pune 411040, Maharashtra, India
| | - Anupam Singh
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh 160011, India
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7
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Rivera-Gonzalez O, Wilson NA, Coats LE, Taylor EB, Speed JS. Endothelin receptor antagonism improves glucose handling, dyslipidemia, and adipose tissue inflammation in obese mice. Clin Sci (Lond) 2021; 135:1773-1789. [PMID: 34278410 PMCID: PMC8650556 DOI: 10.1042/cs20210549] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/13/2021] [Accepted: 07/16/2021] [Indexed: 12/11/2022]
Abstract
Endothelin-1 (ET-1) is elevated in patients with obesity; however, its contribution to the pathophysiology related to obesity is not fully understood. We hypothesized that high ET-1 levels cause dyslipidemia, inflammation, and insulin resistance within the adipose tissue of obese mice. To test this hypothesis, male C57BL/6J mice were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks followed by 2 weeks of treatment with either vehicle, atrasentan (ETA receptor antagonist, 10 mg/kg/day) or bosentan (ETA/ETB receptor antagonist, 100 mg/kg/day). Atrasentan and bosentan lowered circulating non-esterified free fatty acids and triglycerides seen in HFD mice, while atrasentan-treated mice had significantly lower liver triglycerides compared with non-treated HFD mice. ET-1 receptor blockade significantly improved insulin tolerance compared with insulin-resistant HFD mice and lowered expression of genes in epididymal white adipose tissue (eWAT) associated with insulin resistance and inflammation. Flow cytometric analyses of eWAT indicated that HFD mice had significantly higher percentages of both CD4+ and CD8+ T cells compared with NMD mice, which was attenuated by treatment with atrasentan or bosentan. Atrasentan treatment also abolished the decrease in eosinophils seen in HFD mice. Taken together, these data indicate that ETA and ETA/ETB receptor blockade improves peripheral glucose homeostasis, dyslipidemia and liver triglycerides, and also attenuates the pro-inflammatory immune profile in eWAT of mice fed HFD. These data suggest a potential use for ETA and ETA/ETB receptor blockers in the treatment of obesity-associated dyslipidemia and insulin resistance.
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Affiliation(s)
- Osvaldo Rivera-Gonzalez
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A
| | - Natalie A Wilson
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A
| | - Laura E Coats
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A
| | - Erin B Taylor
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A
| | - Joshua S Speed
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A
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Oldenburger A, Birk G, Schlepütz M, Broermann A, Stierstorfer B, Pullen SS, Rippmann JF. Modulation of vascular contraction via soluble guanylate cyclase signaling in a novel ex vivo method using rat precision-cut liver slices. Pharmacol Res Perspect 2021; 9:e00768. [PMID: 34014044 PMCID: PMC8135082 DOI: 10.1002/prp2.768] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 01/05/2023] Open
Abstract
Fibrotic processes in the liver of non-alcoholic steatohepatitis (NASH) patients cause microcirculatory dysfunction in the organ which increases blood vessel resistance and causes portal hypertension. Assessing blood vessel function in the liver is challenging, necessitating the development of novel methods in normal and fibrotic tissue that allow for drug screening and translation toward pre-clinical settings. Cultures of precision cut liver slices (PCLS) from normal and fibrotic rat livers were used for blood vessel function analysis. Live recording of vessel diameter was used to assess the response to endothelin-1, serotonin and soluble guanylate cyclase (sGC) activation. A cascade of contraction and relaxation events in response to serotonin, endothelin-1, Ketanserin and sGC activity could be established using vessel diameter analysis of rat PCLS. Both the sGC activator BI 703704 and the sGC stimulator Riociguat prevented serotonin-induced contraction in PCLS from naive rats. By contrast, PCLS cultures from the rat CCl4 NASH model were only responsive to the sGC activator, thus establishing that the sGC enzyme is rendered non-responsive to nitric oxide under oxidative stress found in fibrotic livers. The role of the sGC pathway for vessel relaxation of fibrotic liver tissue was identified in our model. The obtained data shows that the inhibitory capacities on vessel contraction of sGC compounds can be translated to published preclinical data. Altogether, this novel ex vivo PCLS method allows for the differentiation of drug candidates and the translation of therapeutic approaches towards the clinical use.
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Affiliation(s)
- Anouk Oldenburger
- CardioMetabolic Diseases ResearchBoehringer Ingelheim Pharma GmbH & Co. KGBiberach a.d. RissGermany
| | - Gerald Birk
- Target Discovery SciencesBoehringer Ingelheim Pharma GmbH & Co. KGBiberach an der RissGermany
| | - Marco Schlepütz
- Immunology and Respiratory Diseases ResearchBoehringer Ingelheim Pharma GmbH & Co. KGBiberach an der RissGermany
| | - Andre Broermann
- CardioMetabolic Diseases ResearchBoehringer Ingelheim Pharma GmbH & Co. KGBiberach a.d. RissGermany
| | - Birgit Stierstorfer
- Target Discovery SciencesBoehringer Ingelheim Pharma GmbH & Co. KGBiberach an der RissGermany
| | - Steven S. Pullen
- CardioMetabolic Diseases ResearchBoehringer Ingelheim Pharmaceuticals, IncRidgefieldCTUSA
| | - Jörg F. Rippmann
- Cancer Immunology+Immune ModulationBoehringer Ingelheim Pharma GmbH & Co. KGBiberach a.d. RissGermany
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9
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Kong H, He J, Guo S, Song Q, Xiang D, Tao R, Yu H, Chen G, Huang Z, Ning Q, Huang J. Endothelin receptors promote schistosomiasis-induced hepatic fibrosis via splenic B cells. PLoS Pathog 2020; 16:e1008947. [PMID: 33075079 PMCID: PMC7595619 DOI: 10.1371/journal.ppat.1008947] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 10/29/2020] [Accepted: 08/31/2020] [Indexed: 12/17/2022] Open
Abstract
Endothelin receptors (ETRs) are activated by vasoactive peptide endothelins and involved in the pathogenesis of hepatic fibrosis. However, less is known about the role of ETRs in Schistosoma (S.) japonicum-induced hepatic fibrosis. Here, we show that the expression of ETRs is markedly enhanced in the liver and spleen tissues of patients with schistosome-induced fibrosis, as well as in murine models. Additional analyses have indicated that the expression levels of ETRs in schistosomiasis patients are highly correlated with the portal vein and spleen thickness diameter, both of which represent the severity of fibrosis. Splenomegaly is a characteristic symptom of schistosome infection, and splenic abnormality may promote the progression of hepatic fibrosis. We further demonstrate that elevated levels of ETRs are predominantly expressed on splenic B cells in spleen tissues during infection. Importantly, using a well-studied model of human schistosomiasis, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells characterized by interleukin-10 (IL-10) secretion and regulatory T (Treg) cell-inducing capacity. Our study provides insights into the mechanisms by which ETRs regulate schistosomiasis hepatic fibrosis and highlights the potential of endothelin receptor antagonist as a therapeutic intervention for fibrotic diseases. Schistosomiasis is a serious but neglected tropical infectious disease. which can lead to hepatic fibrosis and death. To date, there are still no approved antifibrotic therapies. Hepatic fibrosis results in portal hypertension and variceal bleeding, and it is the primary cause of mortality from schistosomiasis. Splenomegaly and hypersplenism can manifest following the development of portal hypertension. Accumulating evidence suggests that the spleen plays a critical role in the development of hepatic fibrosis. In this study, using Schistosoma (S.) japonicum in both humans and mice, we show that progressive hepatic schistosomiasis caused elevation of endothelin receptors (ETRs) both in liver and spleen tissues, and the endothelin receptor-producing cells are mainly located in splenic B cells. More importantly, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells during infection. Thus, our study highlights the potential of endothelin receptor antagonist as a therapeutic intervention for schistosomiasis and other fibrotic diseases.
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Affiliation(s)
- Hongyan Kong
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinan He
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shusen Guo
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiqin Song
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dandan Xiang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ran Tao
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haijing Yu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guang Chen
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiaquan Huang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- * E-mail:
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Smecellato FB, Marsilli LRB, Nakamura JE, Jordani MC, Évora PRB, Castro-e-Silva O. Comparative study between fructose 1-6 bisphosphate and histidine-tryptophan-ketoglutarate in liver preservation in rats submitted to total cold ischemia. Acta Cir Bras 2020; 35:e202000603. [PMID: 32667586 PMCID: PMC7357840 DOI: 10.1590/s0102-865020200060000003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/18/2020] [Accepted: 05/22/2020] [Indexed: 11/22/2022] Open
Abstract
Purpose To compare Fructose-1,6-Bisphosphate (FBP) to Histidine-Tryptophan-Ketoglutarate (HTK) in liver preservation at cold ischemia. Methods Male rats (Sprague-Dawley: 280-340g) divided into three groups (n=7): Control; Fructose-1,6-bisphosphate (FBP); Histidine-Tryptophan-Ketoglutarate (HTK). Animals underwent laparotomy-thoracotomy for perfusion of livers with saline. Livers were removed and deposited into solutions. Mitochondria were isolated to determine State 3 (S3), State 4 (S4), Respiratory Control Ratio (RCR) and Swelling (S). Liver enzymes (AST, ALT, LDH) were determined in solution. At tissue, Malondialdehyde (MDA) and Nitrate (NOx) were determined. All parameters were analyzed at 0.6 and 24 hours of hypothermic preservation. Statistics analysis were made by Mann-Whitney test (p<0.05). Results Regarding ALT, there was a difference between FBP-6h/HTK-6h, lower in HTK. Regarding AST, there was a significant difference between FBP-24h/HTK-24h, lower in FBP. Regarding NOx, there was a difference between 0h and 6h, as well as 0h and 24h for both solutions. Regarding S3, there was a significant difference in 24h compared to Control-0h for both solutions, and a significant difference between FBP-6h/FBP-24h. Regarding S4, there was a difference between Control-0h/HTK-24h and FBP-24h/HTK-24h, higher in HTK. There was a difference between Control-0h/FBP-24h for Swelling, higher in FBP. Conclusion Fructose-1,6-Bisphosphate showed better performance at nitrate and aspartate aminotransferase compared to histidine-tryptophan-ketoglutarate.
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Affiliation(s)
- Fernanda Bombonato Smecellato
- Graduate student, Faculdade de Medicina de Marília (FAMEMA), Brazil. Technical procedures; acquisition, analysis and interpretation of data; manuscript preparation
| | - Lucas Ricardo Benfatti Marsilli
- Graduate student, Faculdade de Medicina de Marília (FAMEMA), Brazil. Technical procedures; acquisition, analysis and interpretation of data; manuscript preparation
| | - Julia Eico Nakamura
- Graduate student, Faculdade de Medicina de Marília (FAMEMA), Brazil. Technical procedures; acquisition, analysis and interpretation of data; manuscript preparation
| | - Maria Cecília Jordani
- Master, Biochemistry, Division of Digestive Surgery, Department of Surgery and Anatomy, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirao Preto-SP, Brazil. Acquisition and interpretation of data, statistical analysis
| | - Paulo Roberto Barbosa Évora
- PhD, Full Professor, Division of Thoracic and Cardiovascular Surgery, Department of Surgery and Anatomy, FMRP-USP, Ribeirao Preto-SP, Brazil. Conception and design of the study, manuscript writing, critical revision
| | - Orlando Castro-e-Silva
- PhD, Full Professor, Department of Surgery and Anatomy, FMRP-USP, Ribeirao Preto-SP, Brazil. Conception and design of the study, analysis and interpretation of data, manuscript writing, critical revision
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11
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Elbadry MM, Tharwat M, Mohammad EF, Abdo EF. Diagnostic accuracy of serum endothelin-1 in patients with HCC on top of liver cirrhosis. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-00030-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common cancers and one of the main causes of cancer-related deaths. As the overall survival of patients with cirrhosis has improved and the global incidence of HCC has continued to increase, strategies for the early detection of HCC are urgently needed for better prognosis. In this study, we aimed to assess the accuracy of endothelin-1 in the diagnosis of HCC in cirrhotic patients in comparison with alpha-fetoprotein (AFP) and whether it could predict its vascular spread. This is a case–control study that included 70 cirrhotic patients with or without hepatocellular carcinoma. Patients were subjected to complete medical history taking, clinical examination and laboratory investigations including serum endothelin-1, alpha-fetoprotein, abdominal ultrasound and Triphasic multi-slice computed tomography (CT; abdomen and pelvis). The outcome results obtained for endothelin-1 were used to assess its diagnostic accuracy in HCC diagnosis and the prediction of presence of vascular spread.
Results
There was a statistically significant increase in serum endothelin-1 in HCC in comparison to cirrhotic patients and normal persons (P value < 0.001). Sensitivity, specificity, and positive and negative predictive values at cut-off point of 5.2 pg/ml for HCC were 90%, 100%, 100%, and 90.9% respectively. There was no statistically significant association between serum endothelin-1 level and portal vein thrombosis in HCC (P value = 0.547).
Conclusion
Endothelin-1 has high sensitivity and specificity for diagnosis of hepatocellular carcinoma. However, it has little value for prediction of its vascular spread.
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Abdel-Razik A, Mousa N, Abdelsalam M, Abdelwahab A, Tawfik M, Tawfik AM, Hasan AS, Elhelaly R, El-Wakeel N, Eldars W. Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome. Front Pharmacol 2020; 11:9. [PMID: 32076410 PMCID: PMC7006449 DOI: 10.3389/fphar.2020.00009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 01/06/2020] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND AND PURPOSE Predictors of response to type-1 hepatorenal syndrome (HRS) therapy are urgently needed. This study's purpose is to evaluate the proposed predictors in these patients. METHODS Forty-two type-1 HRS patients with cirrhosis were treated with albumin and terlipressin. Clinical, biochemical, and demographic parameters taken at the onset of therapy and changes in endothelin-1/nitric oxide (ET-1/NO) ratio during therapy were analyzed to check their predictive value. RESULTS Response to treatment (serum creatinine level <1.5 mg/dL at the end of therapy) was shown in 20 patients (48%). Independent predictive variables of response to therapy were early reduction of ET-1/NO ratio ≥0.15 at day 3 of therapy and serum bilirubin baseline <8 mg/dL (area under the receiver operating characteristic curve, 0.751; P < 0.001; specificity, 55%; sensitivity, 85%). Response rates in patients with serum bilirubin level <8 and ≥8 mg/dL were 63% and 20%, respectively (P = 0.008). The corresponding values in patients with an early reduction of ET-1/NO ratio ≥0.15 and <0.15 on day 3 were 85% and 13.6%, respectively (P < 0.001). CONCLUSIONS Early reduction of ET-1/NO ratio and lower serum bilirubin baseline can predict response to type-1 HRS therapy with albumin and terlipressin. Alternative therapy should be investigated for nonresponder type-1 HRS patients.
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Affiliation(s)
- Ahmed Abdel-Razik
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nasser Mousa
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mostafa Abdelsalam
- Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Abdelwahab
- Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mona Tawfik
- Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed M. Tawfik
- Diagnostic & Interventional Radiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmad S. Hasan
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Rania Elhelaly
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Niveen El-Wakeel
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Waleed Eldars
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Ede CJ, Ede R, Brand M. Selective versus non‐selective shunts for the prevention of variceal rebleeding. Cochrane Database Syst Rev 2019; 2019:CD013471. [PMCID: PMC6837277 DOI: 10.1002/14651858.cd013471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/09/2024]
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the benefits and harms of any type of selective shunt versus any type of non‐selective shunt for the prevention of oesophagogastric variceal rebleeding in people with portal hypertension.
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Affiliation(s)
- Chikwendu J Ede
- University of the WitwatersrandDepartment of Surgery7 York RoadJohannesburgSouth Africa2193
| | - Roseline Ede
- University of the WitwatersrandDepartment of Dermatology7 York Road, ParktownJohannesburgSouth AfricaGauteng
| | - Martin Brand
- University of PretoriaDepartment of SurgeryPretoriaSouth Africa0001
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14
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Brand M, Prodehl L, Ede CJ, Cochrane Hepato‐Biliary Group. Surgical portosystemic shunts versus transjugular intrahepatic portosystemic shunt for variceal haemorrhage in people with cirrhosis. Cochrane Database Syst Rev 2018; 10:CD001023. [PMID: 30378107 PMCID: PMC6516991 DOI: 10.1002/14651858.cd001023.pub3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Variceal haemorrhage that is refractory or recurs after pharmacologic and endoscopic therapy requires a portal decompression shunt (either surgical shunts or radiologic shunt, transjugular intrahepatic portosystemic shunt (TIPS)). TIPS has become the shunt of choice; however, is it the preferred option? This review assesses evidence for the comparisons of surgical portosystemic shunts versus TIPS for variceal haemorrhage in people with cirrhotic portal hypertension. OBJECTIVES To assess the benefits and harms of surgical portosystemic shunts versus transjugular intrahepatic portosystemic shunt (TIPS) for treatment of refractory or recurrent variceal haemorrhage in people with cirrhotic portal hypertension. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched on-line trial registries, reference lists of relevant articles, and proceedings of relevant associations for trials that met the inclusion criteria for this review (date of search 8 March 2018). SELECTION CRITERIA Randomised clinical trials comparing surgical portosystemic shunts versus TIPS for the treatment of refractory or recurrent variceal haemorrhage in people with cirrhotic portal hypertension. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials and extracted data using methodological standards expected by Cochrane. We assessed risk of bias according to domains and risk of random errors with Trial Sequential Analysis (TSA). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS We found four randomised clinical trials including 496 adult participants diagnosed with variceal haemorrhage due to cirrhotic portal hypertension. The overall risk of bias in all the trials was judged at high risk. All the trials were conducted in the United States of America (USA). Two of the trials randomised participants to selective surgical shunts versus TIPS. The other two trials randomised participants to non-selective surgical shunts versus TIPS. The diagnosis of liver cirrhosis was by clinical and laboratory findings. We are uncertain whether there is a difference in all-cause mortality at 30 days between surgical portosystemic shunts compared with TIPS (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.44 to 1.99; participants = 496; studies = 4). We are uncertain whether there is a difference in encephalopathy between surgical shunts compared with TIPS (RR 0.56, 95% CI 0.27 to 1.16; participants = 496; studies = 4). We found evidence suggesting an increase in the occurrence of the following harms in the TIPS group compared with surgical shunts: all-cause mortality at five years (RR 0.61, 95% CI 0.42 to 0.90; participants = 496; studies = 4); variceal rebleeding (RR 0.18, 95% CI 0.07 to 0.49; participants = 496; studies = 4); reinterventions (RR 0.13, 95% CI 0.06 to 0.28; participants = 496; studies = 4); and shunt occlusion (RR 0.14, 95% CI 0.04 to 0.51; participants = 496; studies = 4). We could not perform an analysis of health-related quality of life but available evidence appear to suggest improved health-related quality of life in people who received surgical shunt compared with TIPS. We downgraded the certainty of the evidence for all-cause mortality at 30 days and five years, irreversible shunt occlusion, and encephalopathy to very low because of high risk of bias (due to lack of blinding); inconsistency (due to heterogeneity); imprecision (due to small sample sizes of the individual trials and few events); and publication bias (few trials reporting outcomes). We downgraded the certainty of the evidence for variceal rebleeding and reintervention to very low because of high risk of bias (due to lack of blinding); imprecision (due to small sample sizes of the individual trials and few events); and publication bias (few trials reporting outcomes). The small sample sizes and few events did not allow us to produce meaningful trial sequential monitoring boundaries, suggesting plausible random errors in our estimates. AUTHORS' CONCLUSIONS We found evidence suggesting that surgical portosystemic shunts may have benefit over TIPS for treatment of refractory or recurrent variceal haemorrhage in people with cirrhotic portal hypertension. Given the very low-certainty of the available evidence and risks of random errors in our analyses, we have very little confidence in our review findings.
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Affiliation(s)
- Martin Brand
- University of PretoriaDepartment of SurgeryPretoriaSouth Africa0001
| | - Leanne Prodehl
- University of the WitwatersrandDepartment of Surgery1 Jubilee RoadJohannesburgGautengSouth Africa2192
| | - Chikwendu J Ede
- University of the WitwatersrandDepartment of Surgery1 Jubilee RoadJohannesburgGautengSouth Africa2192
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Atwa A, Hegazy R, Mohsen R, Yassin N, Kenawy S. Protective Effects of the Third Generation Vasodilatory Βeta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats. Open Access Maced J Med Sci 2017; 5:880-892. [PMID: 29362613 PMCID: PMC5771289 DOI: 10.3889/oamjms.2017.173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 08/27/2017] [Accepted: 11/25/2017] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS). AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats. MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed. RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment. CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties.
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Affiliation(s)
- Ahmed Atwa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Egypt
| | - Rehab Hegazy
- Department of Pharmacology, Medical Division, National Institution Research, Giza, Egypt
| | - Rania Mohsen
- Departement of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Neamat Yassin
- Department of Pharmacology, Medical Division, National Institution Research, Giza, Egypt
| | - Sanaa Kenawy
- Departement of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Cre recombinase-regulated Endothelin1 transgenic mouse lines: novel tools for analysis of embryonic and adult disorders. Dev Biol 2015; 400:191-201. [PMID: 25725491 DOI: 10.1016/j.ydbio.2015.01.027] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Revised: 12/31/2014] [Accepted: 01/25/2015] [Indexed: 01/06/2023]
Abstract
Endothelin-1 (EDN1) influences both craniofacial and cardiovascular development and a number of adult physiological conditions by binding to one or both of the known endothelin receptors, thus initiating multiple signaling cascades. Animal models containing both conventional and conditional loss of the Edn1 gene have been used to dissect EDN1 function in both embryos and adults. However, while transgenic Edn1 over-expression or targeted genomic insertion of Edn1 has been performed to understand how elevated levels of Edn1 result in or exacerbate disease states, an animal model in which Edn1 over-expression can be achieved in a spatiotemporal-specific manner has not been reported. Here we describe the creation of Edn1 conditional over-expression transgenic mouse lines in which the chicken β-actin promoter and an Edn1 cDNA are separated by a strong stop sequence flanked by loxP sites. In the presence of Cre, the stop cassette is removed, leading to Edn1 expression. Using the Wnt1-Cre strain, in which Cre expression is targeted to the Wnt1-expressing domain of the central nervous system (CNS) from which neural crest cells (NCCs) arise, we show that stable chicken β-actin-Edn1 (CBA-Edn1) transgenic lines with varying EDN1 protein levels develop defects in NCC-derived tissues of the face, though the severity differs between lines. We also show that Edn1 expression can be achieved in other embryonic tissues utilizing other Cre strains, with this expression also resulting in developmental defects. CBA-Edn1 transgenic mice will be useful in investigating diverse aspects of EDN1-mediated-development and disease, including understanding how NCCs achieve and maintain a positional and functional identity and how aberrant EDN1 levels can lead to multiple physiological changes and diseases.
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Chang Y, Qi X, Li Z, Wang F, Wang S, Zhang Z, Xiao C, Ding T, Yang C. Hepatorenal syndrome: insights into the mechanisms of intra-abdominal hypertension. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2013; 6:2523-2528. [PMID: 24228115 PMCID: PMC3816822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Accepted: 09/17/2013] [Indexed: 06/02/2023]
Abstract
OBJECTIVE Hepatorenal syndrome is one of the serious complications of cirrhosis and closely associated with the increasing intra-abdominal pressure (IAP). The study aims to explore the potential mechanism of intra-abdominal hypertension in the development of hepatorenal syndrome in mouse models. METHODS Eighty male mice were randomly divided into model group (subcutaneous injection of carbon tetrachloride) and control group (subcutaneous injection of olive oil). After 12 weeks, parts of the mice were sacrificed and liver histopathology was detected. Then, albumin (30 g/L) and normal saline were separately injected into the peritoneal cavity of mice to induce the different IAP levels (0, 5, 10 and 20cmH2O). Blood urea nitrogen, serum creatinine and renal histopathology were examined 24 hours later. RESULTS Blood urea nitrogen and serum creatinine levels were statistically significant high in the group of IAP= 10 and 20cmH2O as compared with the IAP= 0cmH2O. From results of renal histopathology, the constrictive renal tubular lumen and inflammatory infiltration in the interstitial were observed in groups of IAP= 5 and 10cmH2O. Besides, the formed casts and hyperemia in the renal interstitial could be detected in group of IAP= 20cmH2O. The cellular swelling and edema of renal tubular epithelial cells were found in model group simultaneously. CONCLUSIONS Our study suggested that intra-abdominal hypertension was a significant pathological mechanism and a potential independent risk factor of hepatorenal syndrome.
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Affiliation(s)
- Yizhong Chang
- Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of MedicineShanghai 200065, China
| | - Xiaolong Qi
- Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of MedicineShanghai 200065, China
| | - Zhiwei Li
- Division of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation ArmyBeijing 100039, China
| | - Fei Wang
- Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of MedicineShanghai 200065, China
| | - Shenglan Wang
- Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of MedicineShanghai 200065, China
| | - Zhaojie Zhang
- Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of MedicineShanghai 200065, China
| | - Chaohui Xiao
- Division of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation ArmyBeijing 100039, China
| | - Tongling Ding
- Division of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation ArmyBeijing 100039, China
| | - Changqing Yang
- Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of MedicineShanghai 200065, China
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18
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Khosravi MB, Milani S, Ghaffaripour S, Sahmeddini A, Eghbal MH, Malek-Hosseini SA. Very High Dose Epinephrine for the Treatment of Vasoplegic Syndrome during Liver Transplantation. Int J Organ Transplant Med 2013; 4:32-4. [PMID: 25013651 PMCID: PMC4089302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
A 55-year-old man with hepatitis B and hepatocellular carcinoma was treated with liver transplantation without veno-venous bypass. During the procedure his arterial blood pressure remained at 55/30 mm Hg and did not respond to increasing doses of norepinephrine. Vasoplegia was managed aggressively with the intravenous infusion of high doses of epinephrine.
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Affiliation(s)
- M. B. Khosravi
- Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,Correspondence: Mohammad Bagher Khosravi, Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, Tel : + 98-711-233-7636 , Fax: + 98-711-230-7072, E.mail : Kosravimb@ Sums. ac.ir
| | - S. Milani
- Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - S. Ghaffaripour
- Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - A. Sahmeddini
- Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M. H. Eghbal
- Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - S. A. Malek-Hosseini
- Department of Organ Transplantation, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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Khoshbaten M, Nejad MR, Ansarin K, Fatemi R, Dulaimi DA, Derakhshan F, Jafarinia N, Barford S, Zali MR. The association between clinical symptoms, laboratory findings and serum endothelin 1 concentrations, in cirrhotic patients with and without hepatopulmonary syndrome. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2012; 5:S13-9. [PMID: 24834232 PMCID: PMC4017483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Accepted: 03/08/2012] [Indexed: 11/24/2022]
Abstract
AIM This study evaluated the association between serum endothelin- 1 level and symptoms, clinical examination, laboratory and cardio-respiratory parameters, in patients with cirrhosis compared to controls. BACKGROUND Cirrhosis is associated with significant portal, pulmonary and systemic vascular abnormities. Recent studies have suggested that endothelin -1 may have a significant role in the regulation of vascular tone. PATIENTS AND METHODS In this case - control study, subjects that had been evaluated and diagnosed with biopsy-proven cirrhosis and age-matched controls with no evidence of cardio-vascular or liver disease were recruited. Review of medical records, routine laboratory investigations and cardio-respiratory investigations including echocardiography to look for evidence of hepato-pulmonary syndrome were performed. RESULTS 50 patients were subjects were recruited. The most common aetiology of the cirrhosis was chronic hepatitis B viral infection. 7/50 cases had evidence of the hepatopulmonary syndrome. Among the patients with evidence of the hepatopulmonary syndrome, dyspnoea (100%) and cyanosis (90%) were the most common of the symptoms and signs recorded. Pao2 and arterial - alveolar oxygen gradients were the most sensitive tests in the diagnosis of hepatopulmonary syndrome. Orthodoxy specificity was 100%. The median concentration of serum endothelin-1 in cases with hepatopulmonary syndrome was 1.06+/- 0.015 pg/ml (range 0.92 - 1.21), in cases of sub-clinical hepatopulmonary syndrome, 2.49+/- 0.08 (4.05- 0.93) in patients with cirrhosis but no evidence of hepatopulmonary syndrome criteria 0.85+/-0.74(1.06-0.64) in controls. CONCLUSION There was a significant difference in serum endothelin- 1 levels between patients with cirrhosis and controls, but not between patients with cirrhosis complicated by hepatopulmonary syndrome and controls.
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Affiliation(s)
- Manouchehr Khoshbaten
- Liver and gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Rostami Nejad
- Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Khalil Ansarin
- Pulmonary Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Fatemi
- Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - David Al Dulaimi
- Department of Gastroenterology, Alexandra Hospital, Redditch, UK
| | - Faramarz Derakhshan
- Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nagmeh Jafarinia
- Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sophie Barford
- Department of Gastroenterology, Alexandra Hospital, Redditch, UK
| | - Mohammad Reza Zali
- Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Janas RM, Janas J, Warnawin K, Szalecki M. Role of the rat gastrointestinal mucosa in catabolism of endothelin peptides. ACTA ACUST UNITED AC 2008; 151:7-13. [PMID: 18804491 DOI: 10.1016/j.regpep.2008.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2007] [Revised: 07/02/2008] [Accepted: 08/25/2008] [Indexed: 10/21/2022]
Abstract
Endothelin-1 is involved in physiology and pathophysiology of the alimentary tract. The peptide modulates blood flow in the gastrointestinal microvasculature and regulates contractility of smooth muscles and, when present in excess, may be an important factor contributing to pathogenesis of various forms of mucosal injury and peristaltic disorders. Mechanisms that regulate endothelin concentration in the gastrointestinal tissues are unknown. Therefore, the aim of our study was to identify and characterize endothelin inactivating peptidases in the rat gastrointestinal mucosa and smooth muscle cells. We have found three high affinity and efficient endothelin-1 inactivating peptidases. The acidic (pH optimum 5.5), membrane-bound, thiorphan- (ED(50) 1.2+/-0.2 nM) and phosphoramidon (ED(50) 150+/-25 pM) sensitive, endothelin-1 inactivating peptidase (K(M) 0.12+/-0.03 microM) was present in the mucosal cells of duodenum and small intestine. The enzyme exhibited high molecular weight (>100 kDa) and characteristics similar to that of the rat and human kidney, acidic metalloendopeptidase that was recently described. Two forms of the unique, low molecular weight (100>MW>30 kDa), alkaline (pH optimum 8.5), specific (K(M) 0.5+/-0.2 microM), thiorphan- and phosphoramidon insensitive, 1,10 phenanthroline inhibitable (ED(50) 0.65+/-0.20 mM, mean+/-S.E.M.) endothelin-1 inactivating peptidase were present exclusively in the duodenal mucosal cells; soluble form in cytosol and membrane-bound form exhibiting an abundance ratio 5:1, respectively. Mucosa of the stomach and large intestine, and gastrointestinal smooth muscle cells do not contain the specific endothelin-1 inactivating peptidases. The enzymes may play a crucial role in regulation of endothelin concentration in the gastrointestinal tissues. Whether impairment of activity of the mucosal endothelin inactivating peptidases, resulting in the increase of concentration of endothelin peptides in gastrointestinal tissues, occurs in various pathological conditions is actually studied in our laboratory.
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Affiliation(s)
- Roman M Janas
- Department of Radioimmunology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-736 Warsaw, Poland.
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Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications. Gastroenterology 2008; 134:1715-28. [PMID: 18471549 DOI: 10.1053/j.gastro.2008.03.007] [Citation(s) in RCA: 233] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2008] [Revised: 03/04/2008] [Accepted: 03/06/2008] [Indexed: 12/12/2022]
Affiliation(s)
- Arun J Sanyal
- Division Of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
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Du QH, Li PT. Pathophysiology and clinical practice analysis on endothelin system and portal hypertension. Shijie Huaren Xiaohua Zazhi 2008; 16:1092-1097. [DOI: 10.11569/wcjd.v16.i10.1092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Portal hypertension (PHT) is a common clinical syndrome which leads to various severe, even lethal complications. The concentration of endothelin-1 (ET-1) in plasma is increased both in human body and PHT animal model. The effect of ET-1 depends on the kind of tissue and the expression of ET-1 receptor in this tissue. However, the expression of ET-1 receptor is not identical even in the same tissue at different PHT phases. This review aims to give an update on the endothelin syetem in PHT and elucidate a potential novel strategy.
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Song HJ, Kim JS, Lee MJ, Nam YS, Sohn UD. Reactive oxygen species mediate ET-1-induced activation of ERK1/2 signaling in cultured feline esophageal smooth muscle cells. Arch Pharm Res 2007; 30:1080-7. [PMID: 17958324 DOI: 10.1007/bf02980241] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Reactive oxygen species (ROS) have been shown to play a critical role in propagating the signals of several growth factors, peptide hormones, and cytokines, such as epidermal growth factor, insulin, and interleukin-1. We investigated a possible role for ROS generation in mediating the action of ET-1 on activation of ERK1/2 in cultured feline esophageal smooth muscle cells (ESMC). Confluent layers of ESMC were stimulated by 10nM ET-1; activation of ERK was examined by western blot analysis with phospho-specific antibodies of ERKs. ET-1 induced ERK1/2 phosphorylation in a dose- and time- dependent manner. ERK1/2 activation by ET-1 reached the maximal levels at 5min showing slight activation up to 20min, and then slowly declined. It was confirmed that the activation of ERK1/2 was reduced by MEK inhibitor PD98059. We observed the dose-dependent inhibitory effect of diphenyleneiodonium (DPI), an inhibitor of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on the ET-1-enhanced ERK1/2 phosphorylation in ESMC. Pretreatment of ESMC with N-acetylcysteine, a ROS scavenger, also attenuated the ET-1-induced ERK1/2 activation. In addition, DPI significantly inhibited the ET-1- induced ROS production when ROS was measured as a function of DCF fluorescence. The results suggest that ROS might be critical mediators of the ET-1-induced ERK1/2 signaling events in ESMC.
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Affiliation(s)
- Hyun Ju Song
- Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea
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24
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Ng CKF, Chan MHM, Tai MHL, Lam CWK. Hepatorenal syndrome. Clin Biochem Rev 2007; 28:11-7. [PMID: 17603637 PMCID: PMC1904420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with critically poor prognosis. The pathophysiological hallmark is severe renal vasoconstriction, resulting from complex changes in splanchnic and general circulations as well as systemic and renal vasoconstrictors and vasodilators. Rapid diagnosis and management are important, since recent treatment modalities including vasoconstrictor therapy can improve short-term outcome and buy time for liver transplantation, which can result in complete recovery.
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Affiliation(s)
- Charles KF Ng
- Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Michael HM Chan
- Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Morris HL Tai
- Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Christopher WK Lam
- Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
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25
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Boursier J, Asfar P, Joly-Guillou ML, Calès P. Infection et rupture de varice œsophagienne au cours de la cirrhose. ACTA ACUST UNITED AC 2007; 31:27-38. [PMID: 17273129 DOI: 10.1016/s0399-8320(07)89324-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Endotoxemia and bacterial infection are frequent in patients with cirrhosis. They alter systemic and splanchnic hemodynamics, worsen coagulation disorders, impair liver function and thus may induce variceal bleeding. In variceal bleeding, bacterial infection favours failure to control bleeding, early rebleeding, and death. In patients with cirrhosis and variceal bleeding, antibiotic-prophylaxis decreases bacterial infection and the incidence of early rebleeding, and, more important, significantly decreases the death rate in these patients.
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Affiliation(s)
- Jérôme Boursier
- Laboratoire HIFIH, UPRES EA 3859, IFR 132, Université, Angers
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Abstract
Endothelin (ET)-1 is a potent vasoconstrictor peptide with pro-inflammatory, mitogenic, and pro-fibrotic properties that is closely involved in both normal renal physiology and pathology. ET-1 exerts a wide variety of biological effects, including constriction of cortical and medullary vessels, mesangial cell contraction, stimulation of extracellular matrix production, and inhibition of sodium and water reabsorption along the collecting duct, effects that are primarily mediated in an autocrine/paracrine manner. Increasing evidence indicates that the ET system is involved in an array of renal disorders. These comprise chronic proteinuric states associated with progressive glomerular and tubulointerstitial fibrosis, including diabetic and hypertensive nephropathy, glomerulonephritis and others. In addition, ET-1 is causally linked to renal disorders characterized by increased renal vascular resistance, including acute ischaemic renal failure, calcineurin inhibitor toxicity, endotoxaemia, hepatorenal syndrome and others. Furthermore, derangement of the ET system may be involved in conditions associated with inappropriate sodium and water retention; for example, in congestive heart failure and hepatic cirrhosis. Both selective and non-selective ET receptor antagonist have been developed and tested in animal models with promising results. As key events in progressive renal injury like inflammation and fibrosis are mediated via both ET(A) and ET(B) receptors, while constrictor effects are primarily transduced by ET(A) receptors, dual ET receptor blockade may be superior over selective ET(A) antagonism. Several compounds have been developed with remarkable effects in several models of acute and progressive renal injury. Thus, clinical studies are required to assess whether these results can be confirmed in humans, hopefully leading to novel and effective therapeutic options with few side effects.
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Affiliation(s)
- W Neuhofer
- Department of Physiology, University of Munich, Munich, Germany.
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Abstract
Endothelin may be involved in many of the vascular abnormalities in patients with cirrhosis, and its overall effects in different tissues may depend on differential expression of endothelin receptors on smooth muscle and endothelial cells
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Affiliation(s)
- P W Angus
- Department of Gastroenterology, Austin Health, Studley Rd, Heidelberg, Australia, 3084.
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28
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Neuhofer W, Gülberg V, Gerbes AL. Endothelin and endothelin receptor antagonism in portopulmonary hypertension. Eur J Clin Invest 2006; 36 Suppl 3:54-61. [PMID: 16919012 DOI: 10.1111/j.1365-2362.2006.01690.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Portopulmonary hypertension (PPHT) is a rare but devastating complication in patients with portal hypertension, characterized by pulmonary arterial obliterative disease with a concomitant rise in pulmonary vascular resistance. A broad body of evidence has accumulated, indicating that endothelin (ET) peptides and their cognate receptors are causally involved in the pathophysiology of pulmonary arterial hypertension (PAH) owing to different aetiologies, including PPHT. In addition, the ET system may be involved in hepatic fibrotic remodelling and portal hypertension. Several experimental models have provided evidence that ET receptor antagonism may have therapeutic potential in PPHT. Initial experience has accumulated during the last 2 years, suggesting that targeting the ET system may have beneficial effects in the clinical setting. In these studies, the orally active, dual ET receptor antagonist bosentan improved pulmonary haemodynamics and functional capacity. These effects were sustained and occurred in the absence of adverse events. If these observations can be corroborated by controlled clinical trials, bosentan would offer several advantages over available therapies, which have major drawbacks owing to their invasive and demanding mode of application.
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Affiliation(s)
- W Neuhofer
- Department of Physiology: University of Munich, Munich, Germany.
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29
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Wadei HM, Mai ML, Ahsan N, Gonwa TA. Hepatorenal syndrome: pathophysiology and management. Clin J Am Soc Nephrol 2006; 1:1066-79. [PMID: 17699328 DOI: 10.2215/cjn.01340406] [Citation(s) in RCA: 150] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Hani M Wadei
- Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Jacksonville, FL 32216, USA
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Abstract
Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance to increased arterial blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel.
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Affiliation(s)
- Jens H Henriksen
- Department of Clinical Physiology, 239 Hvidovre University Hospital, DK-2650 Hvidovre, Denmark.
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Møller S, Bendtsen F, Henriksen JH. Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome. Scand J Gastroenterol 2005; 40:491-500. [PMID: 16036500 DOI: 10.1080/00365520510012064] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Hepatorenal syndrome (HRS) is a functional and reversible impairment of renal function in patients with severe cirrhosis. Major pathophysiological elements include liver dysfunction, a circulatory derangement with central hypovolaemia and neurohumoral activation of potent vasoactive systems leading to a pronounced renal vasoconstriction. The prognosis of patients with HRS is poor but recent research has spread new enthusiasm for treatment. Efforts at treatment should seek to improve liver function, to ameliorate arterial hypotension and central hypovolaemia, and to reduce renal vasoconstriction. Therefore a combined approach should be applied with reduction of portal pressure with e.g. ss-adrenergic blockers and transjugular intrahepatic portosystemic shunt (TIPS), with amelioration of arterial hypotension and central hypovolaemia with vasoconstrictors such as terlipressin and plasma expanders. New experimental treatments with endothelin- and adenosine antagonists and long-acting vasoconstrictors may have a future role in the management of HRS.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology 239, Hvidovre Hospital, University of Copenhagen, DK-2650, Hvidovre, Denmark.
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Huang SC. Endothelin receptors in lower esophageal sphincter circular smooth muscle. ACTA ACUST UNITED AC 2005; 127:27-35. [PMID: 15680467 DOI: 10.1016/j.regpep.2004.10.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2004] [Accepted: 10/21/2004] [Indexed: 10/26/2022]
Abstract
To characterize endothelin (ET) receptors in the lower esophageal sphincter, we measured contraction of transverse strips from the guinea-pig lower esophageal sphincter induced by ET-related peptides and binding of 125I-ET-1 to cell membranes prepared from the lower esophageal sphincter circular muscle. Visualization of 125I-ET-1 binding sites in tissue was performed by autoradiography. ET-1 or ET-2 alone did not cause contraction or relaxation in resting strips. However, in carbachol precontracted lower esophageal sphincter strips, ET-1 and ET-2 caused marked, tetrodotoxin-insensitive relaxation. The ET-1-induced relaxation was abolished by BQ-123, an ETA receptor selective antagonist, but not inhibited by BQ-788, an ETB receptor selective antagonist. ET-3 and sarafotoxin S6c, a selective ETB receptor agonist, did not cause relaxation in the carbachol precontracted muscle strips. These clearly indicate that ETA receptors mediate relaxation. On the other hand, ET-3 and sarafotoxin S6c caused tetrodotoxin and atropine-insensitive contraction in the resting strips. The sarafotoxin S6c-induced contraction was inhibited by BQ-788, but not by BQ-123. Furthermore, ET-1 and ET-2 caused contraction of the resting muscle strips after pretreatment with BQ-123. This ET-1-induced contraction was also inhibited by BQ-788. Taken together, these indicate that ETB receptors mediate contraction. Autoradiography localized 125I-ET-1 binding to the lower esophageal sphincter circular muscle as well as longitudinal muscle of the esophagus. Binding of 125I-ET-1 to cell membranes prepared from the circular smooth muscle was saturable and specific. Analysis of dose-inhibition curves indicated the presence of two classes of receptors, ETA and ETB receptors. These results demonstrate that the guinea-pig lower esophageal sphincter possesses ETA receptors mediating relaxation and ETB receptors mediating contraction.
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Affiliation(s)
- Shih-Che Huang
- Department of Internal Medicine, Tzu Chi General Hospital and Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 970, Taiwan.
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Abstract
Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic hemodynamics in cirrhosis. The most characteristic findings in cirrhotic patients are vasodilatation with low systemic vascular resistance, increased cardiac output, high arterial compliance, secondary activation of counterregulatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system, neuropituitary release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through nitric oxide, calcitonin gene-related peptide, adrenomedullin, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homeostatic regulation in cirrhotic patients with manifest arterial hypertension. This is a topic for future research.
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Affiliation(s)
- Jens H Henriksen
- Department of Clinical Physiology, 239, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark.
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34
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N/A, 朱 焱, 林 勇, 谢 渭. N/A. Shijie Huaren Xiaohua Zazhi 2005; 13:367-370. [DOI: 10.11569/wcjd.v13.i3.367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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