Effect of preconditioning temperature on cardioprotection during global ischemia-reperfusion in the rat heart.

Ischemia-reperfusion injury is known to be deleterious to the myocardium (1,2). However, during open heart surgical procedures, hearts must undergo prolonged periods of induced ischemic arrest followed by reperfusion. To minimize the extent of the ischemic damage, several cardioprotective interventions have been used during open heart surgical procedures to reduce such an injury. These interventions include hypothermia, and hypothermic or normothermic cardioplegia. More recently, the experimental role of ischemic preconditioning (PC) has been identified. PC originated from the hypothesis proposed by Swain et al (3), who showed that a few repetitive ischemic episodes did not cause a cumulative depletion of high-energy phosphate compounds. PC was also reported to limit infarct size (4,5), reduce ischemia and reperfusion arrhythmias (6), and to improve contractile and coronary vascular functions (7). Many studies have tested the possible additive cardioprotection when ischemic PC was combined with hypothermia and cardioplegia. When ischemic PC was added to hypothermic global ischemia, functional reperfusion recovery was either unaffected (8) or improved (9). Furthermore, the addition of cardioplegia had no beneficial effect compared with hypothermic cardioplegia alone (8). A slight improvement in functional recovery reflected by a decrease in end-diastolic pressure was observed when ischemic PC preceded a prolonged period of normothermic cardioplegic arrest (10). However, other investigators reported no effect of such a combination on functional recovery (11). On the other hand, when ischemic PC was combined with an impaired cardioplegic delivery, an increase in the functional recovery was reported (12). Moreover, preconditioning the heart before longer hypothermic cardioplegic periods (ranging from 2.5 h to 12 h) was shown to improve left ventricular contractile functions (13). Coronary vascular functions were reported to either improve (13) or remained unaffected by the same protocol (14). A recent study by Lu et al (15) studied the additive beneficial effects of ischemic PC in patients undergoing cold crystalloid cardioplegic arrest. They observed a significant reduction of both ST-segment elevation and creatine kinase isoenzyme release. Moreover, they showed that contractility was enhanced with improved postoperative functional recovery. On the other hand, Cremer et al (16) reported adverse effects of combining ischemic PC with cold cardioplegic arrest in patients undergoing open heart surgery. Perrault et al (17) observed no additional beneficial effect on the metabolic indices of the heart when ischemic PC was combined with warm cardioplegic arrest. They observed an increase in the release of creatine kinase isoenzyme and in the total production of lactate in the preconditioned patients compared with those given only warm cardioplegia (17). PC for all these studies of global ischemia was achieved at normothermic temperature. There is only one study (18) of regional ischemia in which PC temperature was manipulated from normothermic to hypothermic with significant reduction in the infarct size. The main objective of the present study was to evaluate the comparative efficacy of different PC temperatures, ranging from hypothermic to hyperthermic temperatures, on cardioprotection during prolonged periods of global ischemia in a surgically relevant rat heart model of retrograde aortic perfusion.