Preliminary Results of Topical Hepatic Hypothermia in a Model of Liver Ischemia/Reperfusion Injury in Rats

Abstract

-Background -Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. Objective -To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. Me thods -We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. Results -The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. Conclusion -A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.

Impact of the Intermittent Pringle Maneuver for Predicting Post‐hepatectomy Liver Failure: A Cohort Study of 597 Consecutive Patients

“…One possible reason for this result might have been that improvements in surgical technique and surgical tools may have led to a decrease in blood loss, allowing for the detrimental impact of PM to be highlighted. PM induces ischemia–reperfusion, which leads to microcirculatory disturbance and cellular injury [27]. Although the molecular mechanism remains unclear, it was reported to be related to the release of free radicals derived from oxygen, uncontrolled calcium influx, depletion of adenosine triphosphate, mitochondrial dysfunction and the like [28].…”

Effects of hypothermia on inflammatory cytokine expression in rat liver following asphyxial cardiac arrest

“…The beneficial effects of hypothermia include the decreased hepatic metabolism, the subsequent reduction in oxygen requirement and the inflammatory response regulation (13)(14)(15). Pretreatment with mild hypothermia before ischemia can reduce apoptosis and the production of inflammatory cytokines.…”

Topical hepatic hypothermia associated with ischemic preconditioning. Histopathological and biochemical analysis of ischemia reperfusion damage in a 24 hour model

“…To minimize the effects of LIR, several methods have been studied [7][8][9] , including ischemic preconditioning (IPC) 10,11 and topical hypothermia (TH) 12 . The reduction of oxidative stress with the application of IPC is multifactorial 13,14 , with the activation of specific genes, production of antioxidant enzymes and production of nitric oxide, the latter being a potent vasodilator with important antagonist effects during the ischemia phase 15,16 .…”