Establishing a Brain-Death Donor Model in Pigs

Sereinigg, Michael; Stiegler, P.; Puntschart, A.; Seifert-Held, Thomas; Zmugg, Gerda; Wiederstein-Grasser, Iris; Marte, W.; Marko, T.; Bradatsch, Andrea; Tscheliessnigg, Karlheinz; Stadlbauer, Vanessa

doi:10.1016/j.transproceed.2012.07.105

Cited by 7 publications

(10 citation statements)

References 38 publications

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“…The balloon of the catheter was inflated with saline solution at a rate of 3 ml every 30 seconds to a total volume of 24 ml. Animals were kept at a mean arterial pressure of 50 mmHg and animals were stabilized for 10 hours according to local donor management guidelines [22,24]. 60 min after total inflation of the balloon, anaesthesia was discontinued and after a period of another 60 min, BD diagnostic was performed including testing of brain stem reflexes and painful stimuli by a neurologist, followed by apnoea testing and a 30 min 8 - channel EEG exactly as described elsewhere [25].…”

Section: Methodsmentioning

confidence: 99%

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

et al. 2013

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BackgroundAs organ shortage is increasing, the acceptance of marginal donors increases, which might result in poor organ function and patient survival. Mostly, organ damage is caused during brain death (BD), cold ischemic time (CIT) or after reperfusion due to oxidative stress or the induction of apoptosis. The aim of this study was to study a panel of genes involved in oxidative stress and apoptosis and compare these findings with immunohistochemistry from a BD and living donation (LD) pig model and after cold ischemia time (CIT).MethodsBD was induced in pigs; after 12 h organ retrieval was performed; heart, liver and kidney tissue specimens were collected in the BD (n = 6) and in a LD model (n = 6). PCR analysis for NFKB1, GSS, SOD2, PPAR-alpha, OXSR1, BAX, BCL2L1, and HSP 70.2 was performed and immunohistochemistry used to show apoptosis and nitrosative stress induced cell damage.ResultsIn heart tissue of BD BAX, BCL2L1 and HSP 70.2 increased significantly after CIT. Only SOD2 was over-expressed after CIT in BD liver tissue. In kidney tissue, BCL2L1, NFKB, OXSR1, SOD2 and HSP 70.2 expression was significantly elevated in LD. Immunohistochemistry showed a significant increase in activated Caspase 3 and nitrotyrosine positive cells after CIT in BD in liver and in kidney tissue but not in heart tissue.ConclusionThe up-regulation of protective and apoptotic genes seems to be divergent in the different organs in the BD and LD setting; however, immunohistochemistry revealed more apoptotic and nitrotyrosine positive cells in the BD setting in liver and kidney tissue whereas in heart tissue both BD and LD showed an increase.

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Section: Methodsmentioning

confidence: 99%

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

et al. 2013

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“…Interventions utilised in human BD donors, such as fluid or vasoactive agent administration, may have significant effects on genomic expression of inflammatory mediators [ 16 , 17 ], further limiting the ability of small animal models to replicate comprehensive, modern, intensive care monitoring and management. To begin to address these issues, porcine models have been extended to 24 h [ 18 , 19 ]. Zhai et al .…”

Section: Introductionmentioning

confidence: 99%

Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury

Watts

Bilska

Diab

et al. 2015

ICMx

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BackgroundUpregulation of the endothelin axis has been observed in pulmonary tissue after brain death, contributing to primary graft dysfunction and ischaemia reperfusion injury. The current study aimed to develop a novel, 24-h, clinically relevant, ovine model of brain death to investigate the profile of the endothelin axis during brain death-associated cardiopulmonary injury. We hypothesised that brain death in sheep would also result in demonstrable injury to other transplantable organs.MethodsTwelve merino cross ewes were randomised into two groups. Following induction of general anaesthesia and placement of invasive monitoring, brain death was induced in six animals by inflation of an extradural catheter. All animals were supported in an intensive care unit environment for 24 h. Animal management reflected current human donor management, including administration of vasopressors, inotropes and hormone resuscitation therapy. Activation of the endothelin axis and transplantable organ injury were assessed using ELISA, immunohistochemistry and standard biochemical markers.ResultsAll animals were successfully supported for 24 h. ELISA suggested early endothelin-1 and big endothelin-1 release, peaking 1 and 6 h after BD, respectively, but there was no difference at 24 h. Immunohistochemistry confirmed the presence of the endothelin axis in pulmonary tissue. Brain dead animals demonstrated tachycardia and hypertension, followed by haemodynamic collapse, typified by a reduction in systemic vascular resistance to 46 ± 1 % of baseline. Mean pulmonary artery pressure rose to 186 ± 20 % of baseline at induction and remained elevated throughout the protocol, reaching 25 ± 2.2 mmHg at 24 h. Right ventricular stroke work increased 25.9 % above baseline by 24 h. Systemic markers of cardiac and hepatocellular injury were significantly elevated, with no evidence of renal dysfunction.ConclusionsThis novel, clinically relevant, ovine model of brain death demonstrated that increased pulmonary artery pressures are observed after brain death. This may contribute to right ventricular dysfunction and pulmonary injury. The development of this model will allow for further investigation of therapeutic strategies to minimise the deleterious effects of brain death on potentially transplantable organs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-015-0067-9) contains supplementary material, which is available to authorized users.

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“…The most recent application is the classic epidural water sac inflation method 9,10 . The rate and amount of water injected is the key to this modeling method, which have reported differences in previous literatures, and caused obvious differences among the established brain death animal models.…”

Section: ■ Discussionmentioning

confidence: 99%

Characterization of the intestinal graft in a swine hypotensive after brain death model

Li¹,

Gao

Chen

et al. 2019

Acta Cir. Bras.

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To establish a hypotensive brain death pig model and observe the effects of hypotension on small bowel donors. Methods: The hypotensive brain death model was produced using the modified intracranial water sac inflation method in ten domestic crossbred pigs. Effects of hypotensive brain death on small bowel tissue morphology were evaluated through changes in intestinal tissue pathology, tight junction protein of the intestinal mucosa and plasma intestinal fatty acid-binding protein (i-FABP) levels. The pathophysiological mechanism was examined based on changes in superior mesenteric artery (SMA) blood flow and systemic hemodynamics. Results: After model establishment, SMA blood flow, and the mean arterial pressure (MAP) significantly decreased, while heart rate increased rapidly and fluctuated significantly. Small bowel tissue morphology and levels of tight junction protein of the intestinal mucosa showed that after model establishment, small bowel tissue injury was gradually aggravated over time (P<0.05). Plasma i-FABP levels significantly increased after brain death (P<0.05). Conclusions: A hypotensive brain death pig model was successfully established using an improved intracranial water sac inflation method. This method offers a possibility of describing the injury mechanisms more clearly during and after brain death.

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Establishing a Brain-Death Donor Model in Pigs

Cited by 7 publications

References 38 publications

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury

Characterization of the intestinal graft in a swine hypotensive after brain death model

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