PRECONDITIONING WITH A SINGLE SHORT EPISODE OF GLOBAL-ISCHEMIA IN THEISOLATED WORKING RAT-HEART - EFFECT ON STRUCTURE, MECHANICAL FUNCTION, AND ENERGY-METABOLISM FOR VARIOUS DURATIONS OF SUSTAINED GLOBAL-ISCHEMIA

Purpose Preconditioning in the setting of global ischemia, using funct ional recovery during reperfusion as the endpoint, has recently been d emonstrated in the isolated perfused rat heart. It has been suggested that its beneficial actions have a metabolic basis. The isolated rat h eart has not been fully characterized with respect to the metabolic, f unctional, and structural changes associated with this phenomenon in t he setting of global ischemia. The purpose of this study was to determ ine (1) the time course of protection conferred by a single episode (5 minutes) of preconditioning; (2) changes in tissue high energy phosph ate, lactate, and glycogen levels at different time intervals; and (3) morphological appearance of the heart at the end of ischemia as well as after reperfusion. Methods Isolated perfused working rat hearts wer e used. Preconditioning consisted of a single episode of 5 minutes of global ischemia and 15 minutes of reperfusion. Preconditioned and non- preconditioned hearts were subjected to global ischemia of 20-35 minut es duration. Functional recovery, energy metabolism (high energy phosp hates, lactate, and glycogen), and structural appearance were studied at different stages. Results The functional recovery of the preconditi oned hearts was significantly higher than in the corresponding nonprec onditioned group during reperfusion for all durations of ischemia long er than 25 minutes. The degree of protection observed was less than re ported previously. A minor degree of energy sparing was reflected by d ifferences in the rate of depletion of glycogen and accumulation of ti ssue lactate during the sustained episode of ischemia. Semiquantitativ e light microscopy evaluation revealed that ischemia-induced structura l damage was less in the preconditioned hearts, both at the end of the sustained ischemic episode as well as after reperfusion. Conclusions A single episode of global ischemia successfully preconditions the iso lated working rat heart. The protection elicited was demonstrated on a functional and structural level, and was accompanied by a small energ y-sparing effect.