Ischemic Preconditioning and Liver Tolerance to Warm or Cold Ischemia: Experimental Studies in Large Animals

Compagnon, Philippe; Lindell, Susanne L.; Ametani, Mary S.; Gilligan, Barbara J.; Wang, Hongbing; D’Alessandro, Anthony M.; Southard, James H.; Mangino, Martin J.

doi:10.1097/01.tp.0000164146.21136.0b

Cited by 25 publications

(28 citation statements)

References 49 publications

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“…Regarding both TUNEL results and enzyme levels, single direct application of Epo into the portal vein appears to be superior to pretreatment with consecutive subcutaneous injections. Whereas apoptotic activity was high in the early phase 6 h after I/R injury (62.10% apoptosis rate in the control group) apoptotic activity decreased extensively within the next hours leaving only few apoptotic cells 12 h after reperfusion and hardly any apoptosis at all after 24 h. This phenomenon has been described by various authors suggesting a rapid clearance and processing of apoptotic cells within the damaged organ [9,[17][18][19]32] .…”

Section: Discussionmentioning

confidence: 70%

“…Sepodes et al [16] recently published a study showing protective capacities of Epo in liver ischemia. Numerous agents have been investigated extensively in the past as potential protectors of I/R injury yet clinical relevance and applicability have been limited [17][18][19] . The application of steroids has been shown to reduce cellular damage although side effects such as immunological depression and extensive destabilization of glucose metabolism can be a problem [20] .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, warm and cold ischemic times as well as reperfusion damage are major concerns in liver transplantation where damage to the donor organ is unavoidable to some extent due to logistics and time of shipping even in the most professional setting [17] . 72 rats were allocated to three groups: Group 1 (n = 24) received pretreatment with one injection of Epo per day for 3 consecutive days with a cumulative dose of 1,000 IU s.c. (4,000 IU/kg b.w.)…”

Section: Introductionmentioning

confidence: 99%

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Erythropoietin Reduces Ischemia-Reperfusion Injury in the Rat Liver

et al. 2007

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Background: Human recombinant erythropoietin (Epo) has recently been shown to be a potent protector of ischemic damage in various organ systems. A significant reduction of stroke injury following cerebral ischemia has been postulated as well as improved cardiomyocyte function after myocardial infarction in tissue pretreated with Epo. It was the aim of this study to evaluate the effects of Epo in liver ischemia. Material and Methods: Rats were subjected to 45 min of warm hepatic ischemia. Animals were either pretreated with 1,000 IU of Epo in three doses or received 1,000 IU into the portal vein 30 min before ischemia. Control animals received saline at the same time points before ischemia. Animals were than sacrificed 6, 12, 24, 48 h and 7 days after surgery and transaminases were measured. Liver specimens were evaluated regarding apoptosis, necrosis and regeneration capacity. Results: Apoptosis rates were dramatically reduced in animals pretreated with Epo while mRNA of tumor necrosis factor-α and STAT-3 were upregulated in all groups. Intraportal venous injection displayed superiority to subcutaneous preconditioning. Transaminases were significantly reduced among the Epo-treated animals after 6 and 12 h. Conclusion: Our data suggests a protective effect of Epo in warm hepatic ischemia and reperfusion injury in the rat.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Erythropoietin Reduces Ischemia-Reperfusion Injury in the Rat Liver

et al. 2007

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“…There are at least 4 full reports and an abstract report of lack of efficacy of IPC in the context of LT involving small and large experimental animals and in humans. 22,24,25,60,61 One could speculate that cold ischemia shortly following the IPC somehow blunts the protective effects of IPC. 60 Alternatively, the warm ischemia of IPC, albeit short, aggravates the effects of cold ischemia, as suggested by Azoulay et al 25 Additional work is needed in experimental animal models of LT to fill the existing gaps in the knowledge base related to this.…”

Section: Type Of Ischemiamentioning

confidence: 99%

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

et al. 2008

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Utilization of ischemic preconditioning to ameliorate ischemia/reperfusion injury has been extensively studied in various organs and species for the past two decades. While hepatic ischemic preconditioning in animals has been largely beneficial, translational efforts in the two clinical contexts-liver resection and decreased donor liver transplantation-have yielded mixed results. This review is intended to critically examine the translational data and identify some potential reasons for the disparate clinical results, and highlight some issues for further studies.

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“…Fifteen purpose-bred dogs ( ϳ 20 kg body weight) from Juhasz Limited (Pécs, Hungary) were housed in the Unit for Laboratory Animal quarters for at least 1 week before surgery. Canines were used for the study due to established liver I-R protocols by several groups [19,20] . Canines have an advantage because they are gentle and easy to handle and monogastric like humans.…”

Section: Methodsmentioning

confidence: 99%

Short-Term Effects of N-Acetylcysteine and Ischemic Preconditioning in a Canine Model of Hepatic Ischemia-Reperfusion Injury

et al. 2008

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Aims: We evaluated the possibility that repeated ischemic preconditioning or N-acetylcysteine (NAC) could prevent ischemia-reperfusion injury as determined by indocyanine green plasma disappearance rate (ICG-PDR) or has favorable hemodynamic effects during reperfusion in an in vivo canine liver model. Methods: Under general anesthesia, 3 groups of mongrel dogs (n = 5 per group) were subjected to (1) 60-min hepatic ischemia, (2) same ischemia preceded by intravenous administration of 150 mg kg^–1 NAC, and (3) three episodes of IPC (10-min ischemia followed by 10-min reperfusion) prior to same ischemia. Hepatic reperfusion was maintained for a further 180 min, with hemodynamic and hepatic function parameters monitored throughout. Results: Plasma disappearance rate of indocyanine green and serum levels of aspartate transferase and alanine transferase showed no significant differences between groups. Although liver injury was obvious, reflected by hemodynamic, blood gas, and liver function tests, NAC and IPC failed to prevent decay in hepatic function in this canine model. Conclusion: The results do not support the hypothesis that short-term use of NAC and IPC is beneficial in hepatic surgery.

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Ischemic Preconditioning and Liver Tolerance to Warm or Cold Ischemia: Experimental Studies in Large Animals

Cited by 25 publications

References 49 publications

Erythropoietin Reduces Ischemia-Reperfusion Injury in the Rat Liver

Erythropoietin Reduces Ischemia-Reperfusion Injury in the Rat Liver

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

Short-Term Effects of N-Acetylcysteine and Ischemic Preconditioning in a Canine Model of Hepatic Ischemia-Reperfusion Injury

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