A comparison of hepatic ischemia/hypoxia-reperfusion injury models

摘要

Introduction: A number of hepatic ischemia/hypoxia-reperfusion models have been described. This study characterised the functional and structural changes induced by the most commonly used in vivo and in situ models for hypoxia/ischemia-reperfusion in the rat liver. Methods: A range of no-flow, slow-flow and lobar ischemia and reperfusion models were established in the rat liver. Changes following reperfusion were monitored using physiological, biochemical, histological and pharmacological assessments, including bile production, oxygen consumption, lignocaine extraction, enzyme release, and disposition of exogenous markers. Results: Short periods of hepatic ischemia/hypoxia-reperfusion led to minimal changes in liver function whereas long periods of ischemia-reperfusion led to substantial liver injury. The most severe injury was found with the slow flow, reflow model. The formation of cell vacuoles, blebs and focal hepatitis were the most important liver morphological changes observed as a consequence of ischemia/hypoxia. The major liver histological findings after reperfusion were dispersed apoptosis and local necrosis. Hepatic ischemia/hypoxia-reperfusion was also associated with significant changes in the hepatic extracellular and intracellular spaces. Discussion: The morphology and function of the liver associated with a range of hepatic ischemia/hypoxia-reperfusion models varies with the duration of the insult and between models. The choice of model is therefore an important consideration in seeking to resolve any particular hypothesis associated with hepatic ischemia/hypoxia-reperfusion.