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Yoshida K. Comparison of Low and High Doses of Pentobarbital or Thiopental for Euthanasia of Isoflurane-anesthetized Pigs. JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE : JAALAS 2023; 62:185-188. [PMID: 36889741 PMCID: PMC10078932 DOI: 10.30802/aalas-jaalas-22-000093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 12/06/2022] [Accepted: 01/19/2023] [Indexed: 03/10/2023]
Abstract
Barbiturate overdose is a common method for euthanizing pigs. However, barbiturates can cause tissue damage and may affect experimental results, so the minimal dose should be used. The minimal dose of barbiturate for euthanasia in pigs under isoflurane anesthesia has not yet been determined. In this study, we compared the effect of low and high doses of 2 barbiturates (pentobarbital, 30 or 60 mg/kg; thiopental, 20 and 40 mg/kg) on hemodynamic parameters and time to cardiac arrest in female pigs maintained on isoflurane. Acute decreases in blood pressure and end-tidal CO₂ occurred in all pigs shortly after administration of the barbiturate. However, these changes were not different between either of the high- and low dose groups. Cardiac arrest occurred significantly faster for high dose as compared with low dose thiopental groups, but this parameter was different between the 2 pentobarbital groups. The bispectral index fell immediately after dosing, in all pigs, but no significant differences were observed in the time needed to achieve 0 for the high or low-doses of either drug. In pigs maintained on isoflurane, a low dose of barbiturates is adequate for euthanasia and may result in less tissue damage.
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Affiliation(s)
- Kota Yoshida
- Institute for Advancing Science Miyazaki, Boston Scientific, Miyazaki, Japan;,
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Microbial Translocation and Perinatal Asphyxia/Hypoxia: A Systematic Review. Diagnostics (Basel) 2022; 12:diagnostics12010214. [PMID: 35054381 PMCID: PMC8775023 DOI: 10.3390/diagnostics12010214] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/05/2022] [Accepted: 01/14/2022] [Indexed: 12/15/2022] Open
Abstract
The microbiome is vital for the proper function of the gastrointestinal tract (GIT) and the maintenance of overall wellbeing. Gut ischemia may lead to disruption of the intestinal mucosal barrier, resulting in bacterial translocation. In this systematic review, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines, we constructed a search query using the PICOT (Patient, Intervention, Comparison, Outcome, Time) framework. Eligible studies reported in PubMed, up to April 2021 were selected, from which, 57 publications’ data were included. According to these, escape of intraluminal potentially harmful factors into the systemic circulation and their transmission to distant organs and tissues, in utero, at birth, or immediately after, can be caused by reduced blood oxygenation. Various factors are involved in this situation. The GIT is a target organ, with high sensitivity to ischemia–hypoxia, and even short periods of ischemia may cause significant local tissue damage. Fetal hypoxia and perinatal asphyxia reduce bowel motility, especially in preterm neonates. Despite the fact that microbiome arouse the interest of scientists in recent decades, the pathophysiologic patterns which mediate in perinatal hypoxia/asphyxia conditions and gut function have not yet been well understood.
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Solevåg AL, Cheung PY, Lie H, O’Reilly M, Aziz K, Nakstad B, Schmölzer GM. Chest compressions in newborn animal models: A review. Resuscitation 2015; 96:151-5. [DOI: 10.1016/j.resuscitation.2015.08.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 07/22/2015] [Accepted: 08/02/2015] [Indexed: 11/25/2022]
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Gerosa C, Iacovidou N, Argyri I, Fanni D, Papalois A, Aroni F, Faa G, Xanthos T, Fanos V. Histopathology of renal asphyxia in newborn piglets: Individual susceptibility to tubular changes. World J Nephrol 2015; 4:313-318. [PMID: 25949946 PMCID: PMC4419142 DOI: 10.5527/wjn.v4.i2.313] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Revised: 09/08/2014] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze the effects on the kidney of hypoxia-reoxygenation in an experimental model of normocapnic asphyxia.
METHODS: To this end, 40 newborn Landrace/Large-White piglets aged 1-4 d were studied in this work. Hypoxia was induced by decreasing the inspired fiO2 to 0.06-0.08. Animals were resuscitated with different fiO2 and subdivided into 4 groups: group 1, 2, 3 and 4 received 18%, 21%, 40% and 100% O2 respectively. Macroscopic examination was carried out to evidence possible pathological features. Tissue sample were obtained from both kidneys. Four or five micron paraffin sections were stained with H-E and PAS stain and examined under an optical microscope.
RESULTS: Pathological changes, mainly affecting tubular cells, were observed in the vast majority of kidneys of asphyxiated piglets. The most frequent tubular changes were: tubular casts (95%), tubular dilatation (87.5%), tubular vacuolization (70%), tubular eosinophilia (52.5%), sloughing (50%), fragmentation of the brush border (50%), oedema (32.5%), apoptosis (15%) and glomerular changes (meningeal cell proliferation, capsular adhesion between the flocculus and Bowman’s capsule, glomerulosclerosis and fibrous or cellular crescents associated with collapse of the glomerular tuft). Statistical analysis was carried out on changes observed when the animals were allocated in the 4 groups (χ2-test 0.05). The statistical analysis showed no evidence of differences regarding kidney lesions among the animals groups.
CONCLUSION: Our data show that renal pathology in newborn piglets is characterized by interindividual variability to hypoxia and is not associated with oxygen concentration.
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Casey-Trott TM, Millman ST, Turner PV, Nykamp SG, Lawlis PC, Widowski TM. Effectiveness of a nonpenetrating captive bolt for euthanasia of 3 kg to 9 kg pigs1. J Anim Sci 2014; 92:5166-74. [DOI: 10.2527/jas.2014-7980] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- T. M. Casey-Trott
- Department of Animal and Poultry Science, University of Guelph, Guelph, ON, Canada N1G 2W1
| | - S. T. Millman
- Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames 50011-1250
| | - P. V. Turner
- Department of Pathobiology, University of Guelph, Guelph, ON, Canada N1G 2W1
| | - S. G. Nykamp
- Ontario Veterinary College, Health Sciences Centre, Primary Healthcare Centre, Guelph, ON, Canada N1G 2W1
| | - P. C. Lawlis
- Ontario Ministry of Agriculture and Food, Guelph, ON, Canada N1G 4Y2
| | - T. M. Widowski
- Department of Animal and Poultry Science, University of Guelph, Guelph, ON, Canada N1G 2W1
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Faa G, Fanos V, Fanni D, Gerosa C, Faa A, Fraschini M, Pais ME, Di Felice E, Papalois A, Varsami M, Xanthos T, Iacovidou N. Reoxygenation of asphyxiated newborn piglets: administration of 100% oxygen causes significantly higher apoptosis in cortical neurons, as compared to 21%. BIOMED RESEARCH INTERNATIONAL 2014; 2014:476349. [PMID: 24783208 PMCID: PMC3982623 DOI: 10.1155/2014/476349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 01/22/2014] [Accepted: 02/07/2014] [Indexed: 10/29/2022]
Abstract
OBJECTIVE Evaluation of neuronal changes in an animal experimental model of normocapnic hypoxia- reoxygenation. MATERIALS AND METHODS Fifty male piglets were the study subjects; normocapnic hypoxia was induced in 40 piglets and ten were sham-operated (controls). When bradycardia and/or severe hypotension occurred, reoxygenation was initiated. Animals were allocated in 4 groups according to the oxygen concentration, they were resuscitated with 18%, 21%, 40%, and 100% O2. Persisting asystole despite 10 minutes of cardiopulmonary resuscitation and return of spontaneous circulation were the endpoints of the experiment. Surviving animals were euthanized and brain cortex samples were collected, hematoxylin and eosin-stained, and examined for apoptotic bodies observing 10 consecutive high power fields. RESULTS Histological examination of the control group did not show any pathological change. On the contrary, apoptosis of neurons was found in 87.5% of treated animals. When specimens were examined according to the oxygen concentration used for resuscitation, we found marked intergroup variability; a higher percentage of apoptotic neurons was observed in piglets of group 4 (100% oxygen) compared to the others (P=0.001). CONCLUSIONS This preliminary data shows that normocapnic hypoxia and reoxygenation in Landrace/Large White piglets resulted in significant histological changes in the brain cortex. The degree of pathological changes in cortical neurons was significantly associated with the oxygen concentration used for reoxygenation, with a higher percentage of apoptotic neurons being observed in piglets reoxygenated with 100% compared to 18% O2 and to 21% O2.
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Affiliation(s)
- G. Faa
- Department of Surgery, Section of Pathology, University of Cagliari, Via Ospedale, Sardinia, 09100 Cagliari, Italy
| | - V. Fanos
- Department of Surgery, Section of Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, University of Cagliari, 09100 Cagliari, Italy
| | - D. Fanni
- Department of Surgery, Section of Pathology, University of Cagliari, Via Ospedale, Sardinia, 09100 Cagliari, Italy
| | - C. Gerosa
- Department of Surgery, Section of Pathology, University of Cagliari, Via Ospedale, Sardinia, 09100 Cagliari, Italy
| | - A. Faa
- Department of Surgery, Section of Pathology, University of Cagliari, Via Ospedale, Sardinia, 09100 Cagliari, Italy
| | - M. Fraschini
- Department of Electrical and Electronic Engineering (DIEE), University of Cagliari, 09100 Cagliari, Italy
| | - M. E. Pais
- Department of Surgery, Section of Pathology, University of Cagliari, Via Ospedale, Sardinia, 09100 Cagliari, Italy
| | - E. Di Felice
- Department of Surgery, Section of Pathology, University of Cagliari, Via Ospedale, Sardinia, 09100 Cagliari, Italy
| | - A. Papalois
- ELPEN Research-Experimental Centre, Athens, Greece
| | - M. Varsami
- National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | - T. Xanthos
- National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | - N. Iacovidou
- National and Kapodistrian University of Athens, Medical School, Athens, Greece
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Hypoxia-induced endothelial damage and microthrombosis in myocardial vessels of newborn landrace/large white piglets. BIOMED RESEARCH INTERNATIONAL 2014; 2014:619284. [PMID: 24729978 PMCID: PMC3960513 DOI: 10.1155/2014/619284] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 01/16/2014] [Accepted: 01/23/2014] [Indexed: 12/30/2022]
Abstract
Objective. Evaluating the presence of endothelial changes in myocardial vessels in an experimental model of hypoxia and resuscitation in newborn piglets. Methods. Fifty male Landrace/Large White neonatal piglets were studied: ten of them were allocated in group A (control group, SHAM-operated). In group B (forty animals, experimental group) normocapnic hypoxia was induced by decreasing inspired concentration of O2 to 6%–8%. When the animals developed bradycardia or severe hypotension, reoxygenation was initiated. The animals of group B were allocated in 4 subgroups of 10, according to the concentration of O2 they were resuscitated with (groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O2, resp.). Results. Control group animals did not show any significant endothelial lesions. Contrarily, endothelial lesions were detected in all experimental group cases. When these lesions were analyzed in the different heart zones, no significant difference in their incidence was observed; analyzing the frequency in the animals of the 4 subgroups, only microthrombosis showed a higher frequency in animals in groups 4 and 3. Conclusions. Endothelial damage represents a diffuse pathological feature in the myocardial vessels of piglets subjected to normocapnic hypoxia and resuscitation suggesting a possible role of hyperoxygenation in aggravating endothelial damage.
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Metabolomics network characterization of resuscitation after normocapnic hypoxia in a newborn piglet model supports the hypothesis that room air is better. BIOMED RESEARCH INTERNATIONAL 2014; 2014:731620. [PMID: 24696864 PMCID: PMC3947697 DOI: 10.1155/2014/731620] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Accepted: 01/05/2014] [Indexed: 01/08/2023]
Abstract
Perinatal asphyxia is attributed to hypoxia and/or ischemia around the time of birth and may lead to multiorgan dysfunction. Aim of this research article is to investigate whether different metabolomic profiles occurred according to oxygen concentration administered at resuscitation. In order to perform the experiment, forty newborn piglets were subjected to normocapnic hypoxia and reoxygenation and were randomly allocated in 4 groups resuscitated with different oxygen concentrations, 18%, 21%, 40%, and 100%, respectively. Urine metabolic profiles at baseline and at hypoxia were analysed by 1H-NMR spectroscopy and metabolites were also identified by multivariate statistical analysis. Metabolic pathways associations were also built up by ingenuity pathway analysis (IPA). Bioinformatics analysis of metabolites characterized the effect of metabolism in the 4 groups; it showed that the 21% of oxygen is the most “physiological” and appropriate concentration to be used for resuscitation. Our data indicate that resuscitation with 21% of oxygen seems to be optimal in terms of survival, rapidity of resuscitation, and metabolic profile in the present animal model. These findings need to be confirmed with metabolomics in human and, if so, the knowledge of the perinatal asphyxia condition may significantly improve.
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Faa A, Xanthos T, Papalois A, Locci A, Pampaloni P, Pais ME, Aroni F, Gazzolo D, Faa G, Iacovidou N. S100B immunoreactivity: a new marker of hypoxia-related cardiac damage in newborn piglets. J Matern Fetal Neonatal Med 2013; 26 Suppl 2:72-76. [PMID: 24059558 DOI: 10.3109/14767058.2013.830410] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE The evaluation of the expression of S100B protein, in the swine heart in an experimental model of hypoxia - reoxygenation. METHODS Normocapnic hypoxia was induced in 40 male Landrace/Large White neonatal piglets by decreasing the inspired concentration of oxygen to 6-8%. When animals developed bradycardia or severe hypotension, reoxygenation was initiated. Piglets were allocated in four groups of 10, according to the oxygen concentration they were reoxygenated with: Group 1, 2, 3 and 4 resuscitated with 18%, 21%, 40% and 100% oxygen, respectively. The animals were further classified into 4 groups according with the time required for reoxygenation: group A (<15 min); group B (16-60 min); group C (>60 min); group D (deceased animals). RESULTS Immunostaining for S100B protein was detected in 14 out of the 40 heart samples (35%), both inside the cytoplasm of cardiomyocytes and as globular deposits in the interstitial spaces. Significant differences were observed among groups 1-4 regarding S100B expression. Reactivity for S100B in cardiac cells was detected in 50%, 50%, 10% and 33% of animals in groups 1 and 2, 3 and 4, respectively. Marked differences were also observed among groups A-D: 75%, 33%, 12% and 22% of the animals in group 1, 2, 3 and 4, respectively, showed reactivity for S100B in the heart. CONCLUSIONS Expression of S100B protein occurred in the heart of some of newborn piglets following severe hypoxia. S100B storage in cardiomyocytes correlates with the different oxygen concentration used during reoxygenation, being higher in piglets reoxygenated with 18% and 21%, and lower in animals reoxygenated with 40% oxygen. Intermediate levels of S100B expression were found in 100% O2-treated animals. The finding of a higher percentage of S100B-immunoreactive hearts in piglets with a fast recovery and the detection of a decreased reactivity in animals with a slow and a very slow recovery clearly indicates S100B protein as an early protective factor with a positive prognostic value in asphyxiated newborn piglets.
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Affiliation(s)
- Armando Faa
- Department of Pathology, University of Cagliari , Cagliari , Italy
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Faa A, Iacovidou N, Xanthos T, Locci A, Pampaloni P, Aroni F, Papalois A, Faa G, Fanos V. Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration. Clinics (Sao Paulo) 2012; 67:503-8. [PMID: 22666796 PMCID: PMC3351247 DOI: 10.6061/clinics/2012(05)16] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2012] [Accepted: 03/28/2012] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE Evaluation of myocardial histological changes in an experimental animal model of neonatal hypoxia-reoxygenation. METHODS Normocapnic hypoxia was induced in 40 male Landrace/Large White piglets. Reoxygenation was initiated when the animals developed bradycardia (HR <60 beats/min) or severe hypotension (MAP <15 mmHg). The animals were divided into four groups based on the oxygen (O(2)) concentration used for reoxygenation; groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O(2), respectively. The animals were further classified into five groups based on the time required for reoxygenation: A: fast recovery (<15 min); B: medium recovery (15-45 min); C: slow recovery (45-90 min); D: very slow recovery (>90 min), and E: nine deceased piglets. RESULTS Histology revealed changes in all heart specimens. Interstitial edema, a wavy arrangement, hypereosinophilia and coagulative necrosis of cardiomyocytes were observed frequently. No differences in the incidence of changes were observed among groups 1-4, whereas marked differences regarding the frequency and the degree of changes were found among groups A-E. Coagulative necrosis was correlated with increased recovery time: this condition was detected post-asphyxia in 14%, 57%, and 100% of piglets with fast, medium, and slow or very slow recovery rates, respectively. CONCLUSIONS The significant myocardial histological changes observed suggest that this experimental model might be a reliable model for investigating human neonatal cardiac hypoxia-related injury. No correlation was observed between the severity of histological changes and the fiO(2) used during reoxygenation. Severe myocardial changes correlated strictly with recovery time, suggesting an unreported individual susceptibility of myocardiocytes to hypoxia, possibly leading to death after the typical time-sequence of events.
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Affiliation(s)
- Armando Faa
- University of Cagliari, Department of Pathology, Italy.
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