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Safraou Y, Krehl K, Meyer T, Mehrgan S, Jordan JEL, Tzschätzsch H, Fischer T, Asbach P, Braun J, Sack I, Guo J. The influence of static portal pressure on liver biophysical properties. Acta Biomater 2023; 169:118-129. [PMID: 37507032 DOI: 10.1016/j.actbio.2023.07.033] [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: 03/28/2023] [Revised: 07/03/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023]
Abstract
The liver is a highly vascularized organ where fluid properties, including vascular pressure, vessel integrity and fluid viscosity, play a critical role in gross mechanical properties. To study the effects of portal pressure, liver confinement, fluid viscosity, and tissue crosslinking on liver stiffness, water diffusion, and vessel size, we applied multiparametric magnetic resonance imaging (mpMRI), including multifrequency magnetic resonance elastography (MRE) and apparent diffusion coefficient (ADC) measurements, to ex vivo livers from healthy male rats (13.6±1.6 weeks) at room temperature. Four scenarios including altered liver confinement, tissue crosslinking, and vascular fluid viscosity were investigated with mpMRI at different portal pressure levels (0-17.5 cmH2O). Our experiments demonstrated that, with increasing portal pressure, rat livers showed higher water content, water diffusivity, and increased vessel sizes quantified by the vessel tissue volume fraction (VTVF). These effects were most pronounced in native, unconfined livers (VTVF: 300±120%, p<0.05, ADC: 88±29%, p<0.01), while still significant under confinement (confined: VTVF: 53±32%, p<0.01, ADC: 28±19%, p<0.05; confined-fixed: VTVF: 52±20%, p<0.001, ADC: 11±2%, p<0.01; confined-viscous: VTVF: 210±110%, p<0.01, ADC: 26±9%, p<0.001). Softening with elevated portal pressure (-12±5, p<0.05) occurred regardless of confinement and fixation. However, the liver stiffened when exposed to a more viscous inflow fluid (11±4%, p<0.001). Taken together, our results elucidate the complex relationship between macroscopic-biophysical parameters of liver tissue measured by mpMRI and vascular-fluid properties. Influenced by portal pressure, vascular permeability, and matrix crosslinking, liver stiffness is sensitive to intrinsic poroelastic properties, which, alongside vascular architecture and water diffusivity, may aid in the differential diagnosis of liver disease. STATEMENT OF SIGNIFICANCE: Using highly controllable ex vivo rat liver phantoms, hepatic biophysical properties such as tissue-vascular structure, stiffness, and water diffusivity were investigated using multiparametric MRI including multifrequency magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). Through elaborate tuning of the experimental conditions such as the static portal pressure, flow viscosity, amount and distribution of fluid content in the liver, we identified the contributions of the fluid component to the overall imaging-based biophysical properties of the liver. Our finding demonstrated the sensitivity of liver stiffness to the hepatic poroelastic properties, which may aid in the differential diagnosis of liver diseases.
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Affiliation(s)
- Yasmine Safraou
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Karolina Krehl
- Department of Veterinary Medicine, Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Freie Universität Berlin
| | - Tom Meyer
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Shahryari Mehrgan
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Jakob Ernst Luis Jordan
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Heiko Tzschätzsch
- Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Thomas Fischer
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Patrick Asbach
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Jürgen Braun
- Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Ingolf Sack
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Jing Guo
- Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
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Sychev DA, Parusov AI, Loranskaya ID, Denisenko NP, Akmalova KA, Sozaeva ZA, Turkina OL, Zastrozhin MS. CYP2D6 gene polymorphic markers role in determining the optimal treatment tactics for portal hypertension in patients with liver cirrhosis. TERAPEVT ARKH 2022; 94:200-208. [DOI: 10.26442/00403660.2022.02.201371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 03/28/2022] [Indexed: 12/16/2022]
Abstract
Aim. To study the polymorphic markers CYP2D6*4 (G1846A, rs3892097), CYP2D6*6 (T1707del, rs5030655), CYP2D6*10 (C100T, rs1065852), CYP2D6*41 (G2988A, rs28371725) and CYP2D6*3 (A2549del, rs4986774) role in treatment optimization of portal hypertension with propranolol in patients with liver cirrhosis (LC).
Materials and methods. The study included 60 patients with LC who received propranolol therapy at a daily dose of 30 mg for 14 days. The efficacy of treatment was assessed by ultrasonography measuring the linear blood flow velocity of portal vein. Genotyping of CYP2D6*4, CYP2D6*6, CYP2D6*10, CYP2D6*41 and CYP2D6*3 was carried out by real-time polymerase chain reaction. Evaluation of the CYP2D6 activity was carried out by determining the ratio of pinoline and its metabolite concentration in morning urine using high performance liquid chromatography with mass spectrometry.
Results. Positive hemodynamics in the form of any increase in the mean linear blood flow velocity of the portal vein compared to baseline was observed in 41 patients. Portal vein mean linear blood flow rate increased from 10.43.9 to 14.74.3 cm/s (p0.001). Of these, 29 patients showed an increase in this indicator by 20% from the initial one with a dynamic of 5.5 cm/s (p0.001). The regression analysis constructed by us revealed the presence of a statistically significant effect of the CYP2D6 gene polymorphic marker G1846A carriage on the propranolol therapeutic effect (p0.05). There was no statistically significant effect of polymorphic markers T1707del, C100T, G2988A, and A2549del of the CYP2D6 gene (p0.05). No convincing reliable dependence of CYP2D6 activity on the severity of LC was revealed (p0.05).
Conclusion. An association was found between CYP2D6 gene polymorphic marker G1846A carriage and the hemodynamic effect of propranolol in patients with LC of the Russian population. There is a more significant positive dynamics of manifestations of portal hypertension on the background of propranolol therapy in carriers of the homozygous GG CYP2D6*4 genotype, in contrast to patients with the heterozygous GA genotype. Based on the results of the study, an algorithm has been developed for personalizing the treatment of patients with LC with nonselective b-adrenergic blockers using the method of CYP2D6 genotyping. Carriage of polymorphic markers T1707del, C100T, G2988A and A2549del gene CYP2D6 does not affect the effectiveness of propranolol therapy in patients with LC.
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Rezayat KA, Zeraati AA, Pezeshki Rad M, Chogan J, Davoudian N, Akhavan Rezayat A, Hoseini SM. Impact of Propranolol on Preventing Renal Dysfunction in Patients with Cirrhosis. Middle East J Dig Dis 2017; 9:206-211. [PMID: 29255578 PMCID: PMC5726333 DOI: 10.15171/mejdd.2017.75] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND One of the earliest diagnostic signs of hepatorenal syndrome in patients suffering from liver cirrhosis is an increase in the renal vascular resistive index (RI). In this study, the impact of propranolol on decreasing this index and to postpone the probability of hepatorenal syndrome has been investigated. METHODS In the current research, 30 patients with liver cirrhosis with different age and sexes have been enrolled. Demographic data and complete medical history have been collected using a specific questionnaire. At first, renal artery Doppler ultrasonography was performed to determine the RI. The patients were then treated with propranolol, and under supervision, the dose of the drug was increased gradually every 3 to 5 days to reach the target of 25% decrease in resting heart rate. One month after reaching the target dose of the medicine, Doppler ultrasonography was repeated for the patients and the second RI was compared with the pretreatment ones. RESULTS According to our results after treatment with propranolol, a significant decrease of RI was observed (p < 0.01). However, there was no significant difference in the glomerular filtration rate (GFR) before and after treatment with propranolol (p = 0.290). In our study, we found that administering propranolol was associated with significant changes in RI and GFR between the patients with compensated and decompensated cirrhosis (mean change: -0.005 ± 0.017 vs. -0.058 ± 0.045; p < 0.01 for RI and -4.226 ± 17.440 vs. 13.486 ± 12.047; p < 0.01 for GFR in patients with compensated and decompensated cirrhosis, respectively). CONCLUSION Propranolol reduces renal vascular RI in patients with cirrhosis. The response rates in the patients with decompensating cirrhosis were significantly higher than the patients with compensating cirrhosis.
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Affiliation(s)
- Kambiz Akhavan Rezayat
- Gastroenterology and Hepatology Research Center, Mashhad University of Medical Sciences, Imam Reza Hospital, Mashhad, Iran
| | - Abbas Ali Zeraati
- Associate Professor of Nephrology, Kidney Transplantation Complications Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masoud Pezeshki Rad
- Department of Radiology, Imam Reza Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jalal Chogan
- Gastroenterology and Hepatology Research Center, Mashhad University of Medical Sciences, Imam Reza Hospital, Mashhad, Iran
| | - Najmeh Davoudian
- Gastroenterology and Hepatology Research Center, Mashhad University of Medical Sciences, Imam Reza Hospital, Mashhad, Iran
| | - Amir Akhavan Rezayat
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mousalreza Hoseini
- Department of Internal Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Zhang F, Duan X, Zhang M, Li Z, He Q, Wang Y, Miao C, Zhong W, Zou X, Zhuge Y. Influence of CYP2D6 and β2-adrenergic receptor gene polymorphisms on the hemodynamic response to propranolol in Chinese Han patients with cirrhosis. J Gastroenterol Hepatol 2016; 31:829-834. [PMID: 26489037 DOI: 10.1111/jgh.13198] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/11/2015] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIM Propranolol is widely used to prevent gastroesophageal variceal bleeding; however, some patients could not benefit from propranolol. This study is to evaluate the relationship between CYP2D6 and β2-adrenergic receptor (β2-AR) gene polymorphisms and the hemodynamic response to propranolol in Chinese Han patients. METHODS The clinical data of patients with gastroesophageal varices undergoing hepatic venous pressure gradient (HVPG) measurement before and 7 days after oral propranolol administration in our department were collected. Four single nucleotide polymorphisms of CYP2D6 and β2-AR genes were detected. The relationship was identified by logistic regression model. RESULTS Thirty patients were involved in the analysis. Sixty milligram propranolol twice each day was well tolerated by all the patients. The initial and secondary average of HVPG was 17.4 ± 5.8 mmHg vs. 13.2 ± 4.8 mmHg, respectively (t = 5.726, P < 0.001). Twenty patients responded to propranolol. The mean reduction value of HVPG was 6.6 ± 3.6 mmHg (range from 3 to 19). Genotype analysis showed: 20 homozygotes for C/C188 and 10 for heterozygous C/T188, 8 homozygotes for G/G4268 and 22 heterozygotes for G/C4268, 14 homozygotes for Gly16 and 10 heterozygotes, and 6 homozygotes for Arg16, 27 homozygotes for Gln27 and 3 heterozygotes. The multivariate logistic regression analysis indicated that CYP2D6 (188C>T) genotype was an independent predicting factor for HVPG response to propranolol (P = 0.033). CONCLUSIONS CYP2D6 (188C>T) gene polymorphisms influence the hemodynamic response to propranolol in this population of Chinese Han patients with gastroesophageal varices. However, HVPG response cannot be completely predicted from CYP2D6 and β2-AR gene polymorphisms.
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Affiliation(s)
- Feng Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xuhong Duan
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Ming Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhenlei Li
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Qibin He
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yi Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Chengcheng Miao
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Wenqi Zhong
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoping Zou
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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Villanueva C, Albillos A, Genescà J, Abraldes JG, Calleja JL, Aracil C, Bañares R, Morillas R, Poca M, Peñas B, Augustin S, Garcia-Pagan JC, Pavel O, Bosch J. Development of hyperdynamic circulation and response to β-blockers in compensated cirrhosis with portal hypertension. Hepatology 2016; 63:197-206. [PMID: 26422126 DOI: 10.1002/hep.28264] [Citation(s) in RCA: 138] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 09/28/2015] [Indexed: 12/25/2022]
Abstract
UNLABELLED Nonselective β-blockers are useful to prevent bleeding in patients with cirrhosis and large varices but not to prevent the development of varices in those with compensated cirrhosis and portal hypertension (PHT). This suggests that the evolutionary stage of PHT may influence the response to β-blockers. To characterize the hemodynamic profile of each stage of PHT in compensated cirrhosis and the response to β-blockers according to stage, we performed a prospective, multicenter (tertiary care setting), cross-sectional study. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured in 273 patients with compensated cirrhosis before and after intravenous propranolol (0.15 mg/kg): 194 patients had an HVPG ≥10 mm Hg (clinically significant PHT [CSPH]), with either no varices (n = 80) or small varices (n = 114), and 79 had an HVPG >5 and <10 mm Hg (subclinical PHT). Patients with CSPH had higher liver stiffness (P < 0.001), worse Model for End-Stage Liver Disease score (P < 0.001), more portosystemic collaterals (P = 0.01) and splenomegaly (P = 0.01) on ultrasound, and lower platelet count (P < 0.001) than those with subclinical PHT. Patients with CSPH had lower systemic vascular resistance (1336 ± 423 versus 1469 ± 335 dyne · s · cm(-5) , P < 0.05) and higher cardiac index (3.3 ± 0.9 versus 2.8 ± 0.4 L/min/m(2) , P < 0.01). After propranolol, the HVPG decreased significantly in both groups, although the reduction was greater in those with CSPH (-16 ± 12% versus -8 ± 9%, P < 0.01). The HVPG decreased ≥10% from baseline in 69% of patients with CSPH versus 35% with subclinical PHT (P < 0.001) and decreased ≥20% in 40% versus 13%, respectively (P = 0.001). CONCLUSION Patients with subclinical PHT have less hyperdynamic circulation and significantly lower portal pressure reduction after acute β-blockade than those with CSPH, suggesting that β-blockers are more suitable to prevent decompensation of cirrhosis in patients with CSPH than in earlier stages.
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Affiliation(s)
- Càndid Villanueva
- Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Agustín Albillos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Hospital Universitario Ramón y Cajal (IRYCIS), Universidad de Alcalá, Madrid, Spain
| | - Joan Genescà
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Juan G Abraldes
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malalties Digestives i Metaboliques, IDIBAPS, Hospital Clínic, Barcelona, Spain
| | | | | | - Rafael Bañares
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Hospital General Universitario Gregorio Marañón (IISGM), Facultad de Medicina, Universidad Complutense, Madrid, Spain
| | - Rosa Morillas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Hospital Germans Trias, Badalona, Spain
| | - María Poca
- Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Beatriz Peñas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Hospital Universitario Ramón y Cajal (IRYCIS), Universidad de Alcalá, Madrid, Spain
| | - Salvador Augustin
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Joan Carles Garcia-Pagan
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malalties Digestives i Metaboliques, IDIBAPS, Hospital Clínic, Barcelona, Spain
| | - Oana Pavel
- Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Jaume Bosch
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malalties Digestives i Metaboliques, IDIBAPS, Hospital Clínic, Barcelona, Spain
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de Souza AR, La Mura V, Berzigotti A, García-Pagán JC, Abraldes JG, Bosch J. Prognosis of acute variceal bleeding: Is being on beta-blockers an aggravating factor? A short-term survival analysis. Hepatology 2015; 62:1840-1846. [PMID: 26340692 DOI: 10.1002/hep.28151] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Accepted: 09/01/2015] [Indexed: 12/13/2022]
Abstract
UNLABELLED Nonselective beta-blockers (NSBB) are widely used because they have been proved effective in the prophylaxis of acute variceal bleeding (AVB). However, a significant proportion of patients still experience AVB while on treatment with NSBB, and its impact on prognosis of AVB is unknown. The present study was aimed at assessing the effect of being on prophylactic therapy with NSBB on 5-day failure and 6-week mortality of patients with cirrhosis admitted with AVB. Included were 142 patients: 49 were receiving prophylactic therapy with NSBB (NSBB group) and 93 were not (control group). There were some differences in the baseline characteristics between the groups: higher proportion of alcoholic etiology and active alcoholism (37% versus 10%), higher platelet count, and lower hematocrit at admission in the control group. However, the severity of AVB and initial treatment were similar. Five-day failure occurred in 20% of patients (14% in NSBB versus 24% in controls, P = 0.27). The adjusted odds ratio for 5-day failure under NSBB was 2.46 (95% confidence interval 0.53-11.37, P = 0.25). Nineteen patients (13%) died, and two had liver transplantation within 6 weeks. The probability of survival at 6 weeks was 96% in the NSBB group and 82% in the control group (P = 0.02). After adjusting by propensity score and Model for End-Stage Liver Disease score, the NSBB adjusted odds ratio for 6-week mortality was 0.38 (95% confidence interval 0.05-2.63, P = 0.32). The estimated association between NSBB with both 5-day failure and 6-week mortality was homogenous across all Model for End-Stage Liver Disease spectrums. CONCLUSION Prophylactic NSBB treatment is not a negative prognostic indicator for the short-term survival of patients with cirrhosis admitted with AVB.
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Affiliation(s)
- Andrea Ribeiro de Souza
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona and Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Vincenzo La Mura
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona and Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Annalisa Berzigotti
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona and Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Juan Carlos García-Pagán
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona and Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Juan G Abraldes
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona and Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Jaime Bosch
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona and Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
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Filì D, Falletta C, Luca A, Hernandez Baravoglia C, Clemenza F, Miraglia R, Scardulla C, Tuzzolino F, Vizzini G, Gridelli B, Bosch J. Circulatory response to volume expansion and transjugular intrahepatic portosystemic shunt in refractory ascites: Relationship with diastolic dysfunction. Dig Liver Dis 2015; 47:1052-8. [PMID: 26427586 DOI: 10.1016/j.dld.2015.08.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Revised: 08/25/2015] [Accepted: 08/27/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cirrhotic cardiomyopathy may lead to heart failure in stressful circumstances, such as after transjugular intrahepatic portosystemic shunt (TIPS) placement. AIM To examine whether acute volume expansion predicts haemodynamic changes after TIPS and elicits signs of impending heart failure. METHODS We prospectively evaluated refractory ascites patients (group A) and compensated cirrhotics (group B), who underwent echocardiography, NT-proBNP measurement, and heart catheterization before and after volume load; group A repeated measurements after TIPS. RESULTS 15 patients in group A (80% male; 54±12.4 years) and 8 in group B (100% male; 56±6.2 years) were enrolled. Echocardiography disclosed diastolic dysfunction in 30% and 12.5%, respectively. In group A, volume load and TIPS induced a significant increase in right atrial, mean pulmonary, capillary wedge pressure and cardiac index, and a decrease in systemic vascular resistance (respectively, 4.7±2.8 vs. 9.9±3.6 mmHg; 13.3±3.5 vs. 21.9±5.9 mmHg; 8.3±3.4 vs. 15.4±4.7 mmHg; 3.7±0.7 vs. 4.6±11 t/min/m2; 961±278 vs. 767±285 dynscm(-5); and 10.1±3.3 vs. 14.2±3.4 mmHg; 17.5±4 vs. 25.2±4.2 mmHg; 12.3±4 vs. 19.3±3.4 mmHg; 3.4±0.8 vs. 4.5±0.91l t/min/m2; 779±62 vs. 596±199 dynscm(-5), p<0.001 for all pairs). At 24h, cardiopulmonary pressures returned towards baseline. CONCLUSIONS Acute volume expansion predicted haemodynamic changes immediately after TIPS. All patients had adequate haemodynamic adaptation to TIPS; none developed signs of heart failure.
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Affiliation(s)
- Daniela Filì
- Hepatology Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy.
| | - Calogero Falletta
- Cardiology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Angelo Luca
- Department of Diagnostic and Therapeutic Services, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Cesar Hernandez Baravoglia
- Cardiology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Francesco Clemenza
- Cardiology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Roberto Miraglia
- Radiology Service, Department of Diagnostic and Therapeutic Services, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Cesare Scardulla
- Cardiology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Fabio Tuzzolino
- Department of Economic, Business and Statistical Sciences, University of Palermo, Palermo, Italy
| | - Giovanni Vizzini
- Hepatology Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Bruno Gridelli
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS - ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Jaime Bosch
- Liver Unit, Hospital Clínic, University of Barcelona, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
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Karagiannakis DS, Papatheodoridis G, Vlachogiannakos J. Recent advances in cirrhotic cardiomyopathy. Dig Dis Sci 2015; 60:1141-1151. [PMID: 25404411 DOI: 10.1007/s10620-014-3432-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 11/08/2014] [Indexed: 12/15/2022]
Abstract
Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.
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Affiliation(s)
- Dimitrios S Karagiannakis
- Department of Gastroenterology, Medical School of Athens University, Laiko General Hospital, 17 Agiou Thoma Street, 11527, Athens, Greece,
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9
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Abstract
Cirrhosis is an increasing cause of morbidity and mortality in more developed countries, being the 14th most common cause of death worldwide but fourth in central Europe. Increasingly, cirrhosis has been seen to be not a single disease entity, but one that can be subclassified into distinct clinical prognostic stages, with 1-year mortality ranging from 1% to 57% depending on the stage. We review the current understanding of cirrhosis as a dynamic process and outline current therapeutic options for prevention and treatment of complications of cirrhosis, on the basis of the subclassification in clinical stages. The new concept in management of patients with cirrhosis should be prevention and early intervention to stabilise disease progression and to avoid or delay clinical decompensation and the need for liver transplantation. The challenge in the 21st century is to prevent the need for liver transplantation in as many patients with cirrhosis as possible.
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Affiliation(s)
- Emmanuel A Tsochatzis
- Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute of Liver and Digestive Health, London, UK
| | - Jaime Bosch
- Hepatic Hemodynamic Laboratory, Hospital Clínic-IDIBAPS, University of Barcelona, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - Andrew K Burroughs
- Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute of Liver and Digestive Health, London, UK.
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10
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Suk KT, Kim CH, Park SH, Sung HT, Choi JY, Han KH, Hong SH, Kim DY, Yoon JH, Kim YS, Baik GH, Kim JB, Kim DJ. Comparison of hepatic venous pressure gradient and two models of end-stage liver disease for predicting the survival in patients with decompensated liver cirrhosis. J Clin Gastroenterol 2012; 46:880-886. [PMID: 22810110 DOI: 10.1097/mcg.0b013e31825f2622] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS We evaluated the efficacy of initial and follow-up hepatic venous pressure gradient (HVPG), models of end-stage liver disease (MELD), and MELD-Na for predicting the survival of patients with decompensated liver cirrhosis (LC). BACKGROUND MELD with/without Na score and HVPG have been important predictors of mortality in patients with LC. STUDY Between January 2006 and 2011, a total of 57 patients with decompensated LC, all of whom underwent >2 HVPG measurements for the confirmation of propranolol dosing, were enrolled. MELD and MELD-Na scores were calculated on the day of HVPG measurement. The prognostic accuracy of the initial and follow-up HVPG, MELD, and MELD-Na were analyzed, and independent factors for mortality were evaluated. RESULTS Ten patients (17.5%) died from LC. Initial HVPG (0.883), initial MELD-Na (0.877), follow-up HVPG (0.829), and follow-up MELD-Na (0.802) showed good area under the receiver operating characteristic curve scores in predicting 1-year mortality. In predicting 2-year mortality, only follow-up HVPG (0.821, cut-off value 18 mm Hg) showed good score. Overall area under the receiver operating characteristic curves (initial and follow-up) were 0.843 and 0.864 in HVPG, 0.721 and 0.674 in MELD, and 0.762 and 0.715 in MELD-Na, respectively. In the Cox regression analysis, only follow-up HVPG (P=0.02; odds ratio, 1.11) was associated with mortality. CONCLUSIONS The efficacy of HVPG for predicting mortality is excellent compared with that of MELD or MELD-Na. Therefore, aside from the confirmation of adequate propranolol dosing, HVPG may be needed for predicting the survival of patients with decompensated LC.
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Affiliation(s)
- Ki Tae Suk
- Department of Internal Medicine #Molecular Medicine, Hallym University College of Medicine, Chuncheon, South Korea
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Davenport A, Ahmad J, Al-Khafaji A, Kellum JA, Genyk YS, Nadim MK. Medical management of hepatorenal syndrome. Nephrol Dial Transplant 2012; 27:34-41. [PMID: 22287700 DOI: 10.1093/ndt/gfr736] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatorenal syndrome (HRS) is defined as the occurrence of renal dysfunction in a patient with end-stage liver cirrhosis in the absence of another identifiable cause of renal failure. The prognosis of HRS remains poor, with a median survival without liver transplantation of <6 months. However, understanding the pathogenesis of HRS has led to the introduction of treatments designed to increase renal perfusion and mean arterial blood pressure using vasopressors and albumin, which has led to improvement in renal function in ∼50% of patients.
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Affiliation(s)
- Andrew Davenport
- Department of Medicine, University College London Medical School, London, UK.
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12
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He XJ, Huang TZ, Wang PJ, Peng XC, Li WC, Wang J, Tang J, Feng N, Yu MH. Morphological and biomechanical remodeling of the hepatic portal vein in a swine model of portal hypertension. Ann Vasc Surg 2011; 26:259-67. [PMID: 22192237 DOI: 10.1016/j.avsg.2011.10.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2011] [Revised: 10/09/2011] [Accepted: 10/17/2011] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To obtain the morphological and biomechanical remodeling of portal veins in swine with portal hypertension (PHT), so as to provide some mechanical references and theoretical basis for clinical practice about PHT. METHODS Twenty white pigs were used in this study, 14 of them were subjected to both carbon tetrachloride- and pentobarbital-containing diet to induce experimental liver cirrhosis and PHT, and the remaining animals served as the normal controls. The morphological remodeling of portal veins was observed. Endothelial nitric oxide synthase expression profile in the vessel wall was assessed at both mRNA and protein level. The biomechanical changes of the hepatic portal veins were evaluated through assessing the following indicators: the incremental elastic modulus, pressure-strain elastic modulus, volume elastic modulus, and the incremental compliance. RESULTS The swine PHT model was successfully established. The percentages for the microstructural components and the histological data significantly changed in the experimental group. Endothelial nitric oxide synthase expression was significantly downregulated in the portal veins of the experimental group. Three incremental elastic moduli (the incremental elastic modulus, pressure-strain elastic modulus, and volume elastic modulus) of the portal veins from PHT animals were significantly larger than those of the controls (P < 0.05), whereas the incremental compliance of hepatic portal vein decreased. CONCLUSIONS Our study suggests that the morphological and biomechanical properties of swine hepatic portal veins change significantly during the PHT process, which may play a critical role in the development of PHT and serve as potential therapeutic targets during clinical practice.
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Affiliation(s)
- Xi-Ju He
- Laboratory of Biomechanics, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
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13
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Abstract
PURPOSE OF REVIEW Patients with cirrhosis have total extracellular fluid overload but central effective circulating hypovolaemia. The resulting neurohumoral compensatory response favours the accumulation of fluids into the peritoneal cavity (ascites) and may hinder renal perfusion (hepatorenal syndrome). Their deranged systemic haemodynamics (hyperdynamic circulatory syndrome) is characterized by elevated cardiac output with decreased systemic vascular resistance and low blood pressure. RECENT FINDINGS Molecular and biological mechanisms determining cirrhosis-induced haemodynamic alterations are progressively being elucidated. The need for a goal-directed assessment of volume resuscitation (especially with volumetric techniques) in patients with cirrhosis is becoming more and more evident. The role of fluid expansion with albumin and the use of splanchnic vasopressors in a variety of cirrhosis-related conditions has recently been investigated. SUMMARY The response to fluid loading in patients with advanced cirrhosis is abnormal, primarily resulting in expansion of their noncentral blood volume compartment. Colloid solutions, in particular albumin, are best used in these patients. Albumin may be effective in preventing the haemodynamic derangements associated with large-volume paracentesis (paracentesis-induced circulatory dysfunction), in preventing renal failure during spontaneous bacterial peritonitis and, in association with splanchnic vasopressors, in caring for patients with the hepatorenal syndrome.
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Abstract
Cardiovascular complications of liver cirrhosis include cardiac dysfunction and abnormalities in the central-, splanchnic,- and peripheral circulation. Vasodilatation prevails, but vascular beds with various degrees of reduced and increased haemodynamic resistance are the results of massive activation of powerful homeostatic, regulatory systems. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being often clinical latent, cirrhotic cardiomyopathy can be unmasked by physical and pharmacological strain. Cardiac failure is an important cause of mortality after liver transplantation and stressful procedures as insertions of transjugular intrahepatic portal systemic shunt (TIPS), peritoneal venous shunting, and other types of surgery. Improvement of liver function has been shown to reverse the cardiovascular complications. The clinical significance is an important topic for future research. At present, no specific treatment can be recommended, and the cardiac failure in cirrhosis should be treated as in non-cirrhotic patients with sodium restriction, diuretics, and beta-adrenergic blocking agents. Special care should be taken with the use of ACE-inhibitors and angiotensin antagonist in these patients.
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Affiliation(s)
- Jens H Henriksen
- Department of Clinical Physiology 239, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Hvidovre, Denmark.
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Abraldes JG, Albillos A, Bañares R, Turnes J, González R, García-Pagán JC, Bosch J. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology 2009; 136:1651-8. [PMID: 19208350 DOI: 10.1053/j.gastro.2009.01.043] [Citation(s) in RCA: 319] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2008] [Revised: 01/13/2009] [Accepted: 01/22/2009] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension. METHODS Fifty-nine patients with cirrhosis and portal hypertension (HVPG > or =12 mm Hg) were randomized to groups that were given simvastatin 20 mg/day for 1 month (increased to 40 mg/day at day 15) or placebo in a double-blind clinical trial. Randomization was stratified according to whether the patient was being treated with beta-adrenergic blockers. We studied splanchnic and systemic hemodynamics and variables of liver function and safety before and after 1 month of treatment. RESULTS Simvastatin significantly decreased HVPG (-8.3%) without deleterious effects in systemic hemodynamics. HVPG decreases were observed in patients who were receiving beta-adrenergic blockers (-11.0%; P = .033) and in those who were not (-5.9%; P = .013). Simvastatin improved hepatic, fractional, and intrinsic clearance of indocyanine green, showing an improvement in effective liver perfusion and function. No significant changes in HVPG and liver function were observed in patients receiving placebo. The number of patients with adverse events did not differ significantly between groups. No patient was withdrawn from the study based on adverse events. CONCLUSIONS Simvastatin decreased HVPG and improved liver perfusion in patients with cirrhosis. These effects were additive with those of beta-adrenergic blockers. The beneficial effects of simvastatin should be confirmed in long-term clinical trials for portal hypertension.
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Affiliation(s)
- Juan G Abraldes
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Spain
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16
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Vilas-Boas WW, Jr ARO, Ribeiro RDC, Vieira RLP, Almeida J, Nadu AP, Silva ACSE, Santos RAS. Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients. World J Gastroenterol 2008; 14:6824-30. [PMID: 19058308 PMCID: PMC2773877 DOI: 10.3748/wjg.14.6824] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [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
AIM: To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not.
METHODS: Patients were allocated into two groups: outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA), Angiotensin(Ang) I, Ang II, and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation, hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components.
RESULTS: PRA, Ang I, Ang II and Ang-(1-7) were significantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang I levels and between Ang II and Ang I were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang II remained unchanged in splanchnic and peripheral circulation in patients under β-blockade, whereas the relationship between Ang II and Ang I was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation, cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup.
CONCLUSION: In LD group, propranolol treatment reduced RAS mediators, but did not change the ratio between Ang-(1-7) and Ang II in splanchnic and peripheral circulation. Furthermore, the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio.
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17
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Li Y, Liu H, Gaskari SA, Tyberg JV, Lee SS. Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide. Am J Physiol Gastrointest Liver Physiol 2008; 295:G252-9. [PMID: 18556420 DOI: 10.1152/ajpgi.00436.2007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
In cirrhosis, despite augmented blood volume, effective circulating volume is decreased. This implies abnormal regulation of blood volume, i.e., venous pooling. Because gut veins are the main blood reservoir, we studied mesenteric venous capacitance and compliance in a rat model of cirrhosis. Cirrhosis was induced by bile duct ligation (4 wk). Controls were sham operated. Changes in first-order mesenteric vein diameters induced by drugs, hemorrhage, and stepwise increases in portal pressure (inflatable cuff) were directly observed by intravital microscopy. Effects of nitric oxide on responses to acute graded hemorrhage were studied by use of selective NO synthase (NOS) isoform inhibitors. Pressures were related to diameters to assess capacitance and compliance. Compared with controls, cirrhotic rats demonstrated increased mesenteric venous capacitance and decreased compliance. Norepinephrine induced venoconstriction but did not affect compliance. Prazosin markedly diminished compliance in controls but not cirrhotics. Conversely, the nonspecific NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) decreased compliance in cirrhotics, but not controls. Tetrodotoxin venodilated controls, venoconstricted cirrhotics, and markedly decreased compliance in both groups. When hemorrhaged, controls rapidly venoconstricted to compensate for initial hypotension, whereas cirrhotic rats remained hypotensive because venoconstriction was severely blunted. Pretreatment with l-NAME or the selective neuronal NOS inhibitors S-methyl-l-thiocitrulline and 7-nitroindazole normalized the homeostatic responses of cirrhotic rats, whereas the selective endothelial-constitutive NOS inhibitor N-iminoethyl-l-ornithine did not affect the response. In conclusion, mesenteric veins of cirrhotic rats showed enhanced capacitance, attenuated compensatory constrictive response to hemorrhage, and decreased compliance. The first two abnormalities were caused by neuronal NOS-derived nitric oxide.
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Affiliation(s)
- Yang Li
- Liver Unit, Gastrointestinal Research Group, Calgary, Alberta, Canada
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18
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Suk KT, Kim MY, Park DH, Kim KH, Jo KW, Hong JH, Kim JW, Kim HS, Kwon SO, Baik SK. Effect of propranolol on portal pressure and systemic hemodynamics in patients with liver cirrhosis and portal hypertension: a prospective study. Gut Liver 2007; 1:159-64. [PMID: 20485633 DOI: 10.5009/gnl.2007.1.2.159] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2007] [Accepted: 12/10/2007] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Propranolol can prevent variceal bleeding by ameliorating portal hypertension. We conducted this study to determine the effect of propranolol on portal hypertension and the optimal required dose in Korean cirrhotic patients. METHODS This study prospectively evaluated 50 patients with cirrhosis who exhibited variceal bleeding. The hepatic venous pressure gradient (HVPG), portal venous flow, heart rate (HR), and blood pressure were assessed both at baseline and at 3 months after the treatment. The initial dose of propranolol (20 mg) was subsequently adjusted until the target HR was reached. Patients in whom HVPG reduced by >20% or to less than 12 mmHg were defined as responders. RESULTS Propranolol significantly (p<0.01) reduced the HVPG (-21+/-26%, mean+/-standard deviation), portal venous flow (-25+/-21%), HR (-20+/-13%), and blood pressure (-3+/-13%). Twenty-nine patients were responders, and the optimal required dose was 154.4 mg. The main complication was dizziness (24%), but this was not serious enough to require medication withdrawal. CONCLUSIONS Propranolol is safe and effective at reducing portal pressure in Korean cirrhotic patients. An effective improvement in portal hypertension requires the dose to be increased until the target HR is reached.
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Affiliation(s)
- Ki Tae Suk
- Department of Internal Medicine and Institute of Lifelong Health, Yonsei University Wonju College of Medicine, Wonju, Korea
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Thalheimer U, Bosch J, Burroughs AK. How to prevent varices from bleeding: shades of grey--the case for nonselective beta blockers. Gastroenterology 2007; 133:2029-36. [PMID: 18054573 DOI: 10.1053/j.gastro.2007.10.028] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2007] [Accepted: 09/27/2007] [Indexed: 12/11/2022]
Affiliation(s)
- Ulrich Thalheimer
- Liver Transplantation and Hepatobiliary Unit, Royal Free Hospital, London, United Kingdom
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20
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Andreu V, Garcia-Pagan JC, Lionetti R, Piera C, Abraldes JG, Bosch J. Effects of propranolol on venous compliance in conscious rats with pre-hepatic portal hypertension. J Hepatol 2006; 44:1040-5. [PMID: 16581151 DOI: 10.1016/j.jhep.2005.10.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2005] [Revised: 10/03/2005] [Accepted: 10/24/2005] [Indexed: 12/29/2022]
Abstract
BACKGROUND/AIMS The venous system is the primary capacitance region in the body. However, the influence of active changes in the venous system on the hemodynamic alterations of portal hypertension is poorly understood. To investigate venous compliance (VC) in conscious partial portal vein ligated rats (PPVL) and the effect of propranolol on VC. METHODS Venous compliance was derived from the relationship between changes in mean circulatory filling pressure (MCFP) and changes in blood volume (BV). Measurements were performed before and after i.v. propranolol (7.5 mg/Kg) or placebo in rats with portal hypertension due to PPVL and sham operated controls. RESULTS PPVL rats had an increased VC when compared to Sham (4.9+/-1.4 vs. 3.7+/-0.9 ml kg-1 mm Hg-1; P<0.02). VC did not change after placebo but was significantly reduced by Propranolol in PPVL (-32.9+/-15.7%; P<0,007). Propranolol did not modify venous compliance in sham operated rats (+10.9+/-13.4%; P=ns). CONCLUSIONS Venous compliance is increased in portal hypertensive rats, suggesting that the venous system contributes to the profound circulatory changes encountered in portal hypertension. The increased venous compliance is markedly attenuated by propranolol, suggesting that this abnormality is related to increased adrenergic activity.
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Affiliation(s)
- Victoria Andreu
- Hepatic Hemodynamic Lab., Liver Unit, Institut Clínic de Malalties Digestives i Metabolisme, Hospital Clínic de Barcelona, Institut de Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
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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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22
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Abstract
Patients with cirrhosis and portal hypertension exhibit characteristic cardiovascular and pulmonary hemodynamic changes. A vasodilatatory state and a hyperdynamic circulation affecting the cardiac and pulmonary functions dominate the circulation. The recently defined cirrhotic cardiomyopathy may affect systolic and diastolic functions, and imply electromechanical abnormalities. In addition, the baroreceptor function and regulation of the circulatory homoeostasis is impaired. Pulmonary dysfunction involves diffusing abnormalities with the development of the hepatopulmonary syndrome and portopulmonary hypertension in some patients. Recent research has focused on the assertion that the hemodynamic and neurohumoral dysregulation are of major importance for the development of the cardiovascular and pulmonary complications in cirrhosis. This aspect is important to take into account in the management of these patients.
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23
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Hernández-Guerra M, López E, Bellot P, Piera C, Turnes J, Abraldes JG, Bosch J, García-Pagán JC. Systemic hemodynamics, vasoactive systems, and plasma volume in patients with severe Budd-Chiari syndrome. Hepatology 2006; 43:27-33. [PMID: 16374846 DOI: 10.1002/hep.20990] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Budd-Chiari syndrome (BCS) causes postsinusoidal portal hypertension, which leads to complications similar to those observed in cirrhosis. However, no studies have investigated whether patients with BCS develop the hyperdynamic circulatory syndrome present in patients with cirrhosis who have portal hypertension. We evaluated systemic and cardiopulmonary hemodynamics, plasma renin activity, aldosterone and norepinephrine levels, and plasma volume in patients with BCS admitted for complications of portal hypertension. BCS patients had mean systemic and cardiopulmonary pressures and cardiac indices that were within the normal range but were significantly different from those of a group of patients with cirrhosis matched by sex, body surface, and liver function (cardiac index 3.1 +/- 0.7 vs. 4.9 +/- 1.2 L.min(-1).m(-2); P < .001; systemic vascular resistance [SVR] index, 2,189 +/- 736 vs. 1,377 +/- 422 dyne.s.cm(-5).m(-2), P < .001). Despite normal systemic vascular resistance, BCS patients had activation of the neurohumoral vasoactive systems, as evidenced by increased plasma renin activity, aldosterone and norepinephrine levels (15.0 +/- 21.5 ng/mL . h, 76.7 +/- 106.8 ng/dL, 586 +/- 868 pg/mL; respectively) and plasma volume expansion. The analysis of individual BCS patients identified that 7 of the 21 patients actually had reduced SVR index. These patients had the greatest plasma volume expansion. A significant inverse correlation between plasma volume and SVR index was observed. In conclusion, patients with BCS had activation of vasoactive neurohumoral systems and expanded plasma volume. This outcome was observed even though most of these patients did not exhibit systemic vasodilation and cardiac output was not increased, in marked contrast with what is observed in patients with cirrhosis.
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Affiliation(s)
- Manuel Hernández-Guerra
- Hepatic Hemodynamic Laboratory, Institut de Malalties Digestives, Hospital Clinic, Institut d'Investigaciones Biomédiques August Pi i Sunyer, Barcelona, Spain
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24
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Ytting H, Henriksen JH, Fuglsang S, Bendtsen F, Møller S. Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis. J Hepatol 2005; 43:637-44. [PMID: 16083986 DOI: 10.1016/j.jhep.2005.04.015] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2004] [Revised: 04/12/2005] [Accepted: 04/16/2005] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIMS The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic venous pressure gradient (HVPG) < 12 mmHg. METHODS Forty-four patients with cirrhosis and HVPG < 12 mmHg underwent a haemodynamic study. They were compared with 36 cirrhotic patients with clinically significant portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS The fraction with prolonged Q-T(c) interval (> 0.440 s(1/2)) was similar in the two cirrhotic groups (49 vs 50%, ns) and significantly above that of the controls (5%, P < 0.005). Q-T(c) was normal in patients with normal HVPG. Likewise, mean Q-T(c) was 0.449 and 0.447 s(1/2) in the two cirrhotic groups (ns), values which are significantly above that of the controls (0.410 s(1/2), P < 0.01). In the mild portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P < 0.02). CONCLUSIONS Delayed repolarisation of the myocardium already occurs in a substantial fraction of patients with cirrhosis with only a mild increase in portal pressure. The prolonged Q-T(c) interval may be related to liver dysfunction and to the presence of portal hypertension.
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Affiliation(s)
- Henriette Ytting
- Department of Clinical Physiology and Nuclear Medicine 239, Hvidovre Hospital, University of Copenhagen, DK-2650 Hvidovre, Denmark
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25
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Ginès P, Terra C, Torre A, Guevara M. [Role of albumin in the treatment of hepatorenal syndrome in cirrhosis]. GASTROENTEROLOGIA Y HEPATOLOGIA 2005; 28:80-4. [PMID: 15710088 DOI: 10.1157/13070706] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- P Ginès
- Unidad de Hepatología, Institut de Malalties Digestives, Hospital Clínic, Barcelona, Spain.
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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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27
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Avram MJ, Krejcie TC, Henthorn TK, Niemann CU. Beta-adrenergic blockade affects initial drug distribution due to decreased cardiac output and altered blood flow distribution. J Pharmacol Exp Ther 2004; 311:617-24. [PMID: 15197245 DOI: 10.1124/jpet.104.070094] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Beta-adrenergic receptor blockers decrease intravenous anesthetic dose requirements. The present study determined the effect of propranolol on indocyanine green and antipyrine disposition from the moment of rapid intravenous injection. Anti-pyrine is a physiological marker that distributes to a volume as large as total body water in a blood flow-dependent manner and is a pharmacokinetic surrogate for many lipophilic drugs, including intravenous anesthetics. Antipyrine and indocyanine green disposition were determined twice in five healthy adult males in this Institutional Review Board-approved study, once during propranolol infusion. After rapid indocyanine green and antipyrine injection, arterial blood samples were collected frequently for 2 min and less frequently thereafter. Plasma indocyanine green and antipyrine concentrations were measured by high-performance liquid chromatography. Indocyanine green and antipyrine disposition were characterized, using SAAM II, by a recirculatory pharmacokinetic model that describes drug disposition from the moment of injection. Parameters were compared using the paired t test. The disposition of indocyanine green demonstrated that propranolol decreased cardiac output at the expense of the fast peripheral (nonsplanchnic) intravascular circuit. The area under the antipyrine concentration versus time relationship was doubled for at least the first 3 min after injection due to both decreased cardiac output and maintenance of nondistributive blood flow at the expense of a two-thirds reduction of blood flow (intercompartmental clearance) to the rapidly equilibrating (fast, splanchnic) tissue volume. The increase in antipyrine area under the curve due to propranolol-induced alteration of initial antipyrine disposition could explain decreased intravenous anesthetic dose requirements in the presence of beta-adrenergic receptor blockade.
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Affiliation(s)
- Michael J Avram
- Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Ward Bldg. 13-199, Chicago, IL 60611-3008, USA.
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28
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29
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Abstract
Chronic hepatitis C infection is associated with significant morbidity and mortality in addition to substantial social and health-related costs. Since the identification of the virus and determination of the HCV genome over a decade ago, considerable progress has been made in the treatment of chronic hepatitis C infection. However, the current standard combination of interferon-based therapies and ribavirin is effective in only 50% of patients. In addition, this combination is expensive, requires lengthy periods of administration, and is associated with significant side effects. Furthermore, no effective preventive measure, such as vaccination, is currently available. A number of newer therapies, including protease and helicase inhibitors, ribozymes, antisense therapies, and therapeutic vaccines, are in preclinical and clinical development and may significantly enhance existing therapeutic options for the future.
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Affiliation(s)
- Anouk Dev
- Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, NC 27715, USA
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30
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Henriksen JH, Bendtsen F, Hansen EF, Møller S. Acute non-selective beta-adrenergic blockade reduces prolonged frequency-adjusted Q-T interval (QTc) in patients with cirrhosis. J Hepatol 2004; 40:239-46. [PMID: 14739094 DOI: 10.1016/j.jhep.2003.10.026] [Citation(s) in RCA: 90] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND/AIMS Earlier studies have shown a prolonged frequency-adjusted Q-T interval (QTc>0.440 s(1/2)) in a substantial fraction of patients with cirrhosis. The effect of beta-blockade on QTc is unknown, and its determination was the aim of the study. METHODS Seventeen patients with cirrhosis received 80 mg propranolol orally during a haemodynamic investigation with measurements at baseline and 90 min after propranolol ingestion. RESULTS Beta-blockade reduced cardiac output (-21%, P<0.001), heart rate (-20%, P<0.001), and the hepatic venous pressure gradient (HVPG, -17%, P<0.02). The mean QTc=0.460 s(1/2) was prolonged compared to 0.410 s(1/2) in age-matched controls (P<0.01). Whereas QTc decreased during beta-blockade in the cirrhotic patients (from 0.460 to 0.440 s(1/2), P<0.01), no effect was found in the subgroup with normal QTc (0.429 vs. 0.422 s(1/2), ns), and a reduction was seen in the patients with prolonged QTc (from 0.488 to 0.456 s(1/2), P<0.01). The percentage decrease in QTc was related to the reduction in HVPG (r=0.48, P=0.03) and cardiac output (r=0.56, P=0.02). CONCLUSIONS Acute non-selective beta-blockade reduces prolonged QTc towards normal values in patients with cirrhosis. The clinical significance of QTc reduction in arrhythmia is a topic for future research.
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Affiliation(s)
- Jens H Henriksen
- Department of Clinical Physiology, University of Copenhagen, 239, Hvidovre Hospital, DK-2650 Hvidovre, Denmark.
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31
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Mandell MS, Durham J, Kumpe D, Trotter JF, Everson GT, Niemann CU. The effects of desflurane and propofol on portosystemic pressure in patients with portal hypertension. Anesth Analg 2003; 97:1573-1577. [PMID: 14633521 DOI: 10.1213/01.ane.0000090741.63156.1b] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
UNLABELLED Physicians perform hepatic venous pressure measurements to guide medical therapy aimed at reducing portal hypertension. These measurements are frequently performed during general anesthesia. Since most general anesthetic drugs reduce liver blood flow, it is likely that hepatic venous pressures will be altered. We therefore examined the effects of two frequently used anesthetic drugs on hepatic venous pressure in a prospective randomized study to determine if pressure measurements taken during general anesthesia were similar to awake values. We studied 21 patients with hepatitis C, excluding patients with hepatofugal flow and portal vein thrombosis. All patients had free and wedged hepatic venous pressures measured awake with sedation and after anesthesia with either propofol or desflurane. Desflurane significantly increased free hepatic venous pressure (11.9 +/- 4.4 to 23.5 +/- 4.1 mm Hg; P < 0.05) and decreased hepatic venous pressure gradient (21.6 +/- 7.4 to 14.7 +/- 5.2 mm Hg; P < 0.05), whereas propofol did not change these variables. We conclude that desflurane, but not propofol, alters hepatic venous pressure measurements from the awake state, significantly increasing free hepatic venous pressure and decreasing the hepatic venous pressure gradient, an indirect measure of portosystemic pressure. Changes in the hepatic venous pressure gradient must be interpreted with caution during desflurane general anesthesia. IMPLICATIONS Desflurane reduces the blood pressure difference between the portal and systemic circulations. This can cause errors in assessment of the success of medical therapy of portal hypertension. Propofol has less effect on the difference between the portal and systemic circulation.
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Affiliation(s)
- M Susan Mandell
- Departments of *Anesthesiology, †Radiology, and ‡Hepatology, University of Colorado Health Sciences Center, Denver; and §Department of Anesthesia and Perioperative Care, University of California, San Francisco
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32
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Henriksen JH, Kiszka-Kanowitz M, Bendtsen F. Review article: volume expansion in patients with cirrhosis. Aliment Pharmacol Ther 2002; 16 Suppl 5:12-23. [PMID: 12423449 DOI: 10.1046/j.1365-2036.16.s5.3.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Adequate size and distribution of the circulating medium are important for cardiovascular function, tissue oxygenation, and fluid homoeostasis. Patients with cirrhosis have cardiovascular dysfunction with a hyperkinetic systemic circulation, abnormal distribution of the blood volume, vasodilation with low systemic vascular resistance, increased whole-body vascular compliance, and increased arterial compliance. The effectiveness and temporal relations of plasma/blood volume expansion depend highly on the type of load (water, saline, oncotic material, red blood cells). Patients with cirrhosis respond in some aspects differently from healthy subjects, owing to their disturbed circulatory function and neurohormonal activation. Thus the increase in cardiac output and suppression of the renin-angiotensin-aldosterone system and sympathetic nervous system during volume expansion may be somewhat blunted, and in advanced cirrhosis, especially the non-central parts of the circulation, including the splanchnic blood volume, are expanded by a volume load. Infusion of oncotic material (preferably albumin) is important in the prevention of post-paracentesis circulatory dysfunction. In conclusion, volume expansion in advanced cirrhosis is qualitatively and quantitatively different from that of healthy subjects, and in those with early cirrhosis. Timely handling is essential, but difficult as it is a balance between the risks of excess extravascular volume loading and further circulatory dysfunction in these patients with a hyperdynamic, but hyporeactive, circulation.
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Affiliation(s)
- J H Henriksen
- Department of linical Physiology 239, Hvidovre Hospital, University of Copenhagen, Denmark.
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33
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Ginès P, Guevara M, De Las Heras D, Arroyo V. Review article: albumin for circulatory support in patients with cirrhosis. Aliment Pharmacol Ther 2002; 16 Suppl 5:24-31. [PMID: 12423450 DOI: 10.1046/j.1365-2036.16.s5.4.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Renal function abnormalities and ascites in cirrhosis are the final consequence of a circulatory dysfunction characterized by marked splanchnic arterial vasodilation. This causes a reduction in effective arterial blood volume and the homoeostatic activation of vasoconstrictor and sodium-retaining systems. Albumin is very effective in preventing renal failure associated with large-volume paracentesis and spontaneous bacterial peritonitis, conditions that are known to cause an impairment of circulatory function in patients with cirrhosis and ascites. Moreover, albumin administration improves survival in patients with spontaneous bacterial peritonitis. In patients with hepatorenal syndrome the administration of vasoconstrictor drugs in combination with albumin improves circulatory and renal function markedly and survival slightly. By contrast, the administration of albumin without vasoconstrictors has marginal or no effects on renal function in this setting.
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Affiliation(s)
- P Ginès
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Barcelona, Spain.
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