Myocardial protection with intermittent cross-clamp fibrillation: does preconditioning play a role?

Objective: Previously, we showed intermittent cross-clamp fibrillation afforded equivalent protection to cardioplegia. This study examined whether protection induced by intermittent cross-clamp fibrillation involves an ischemic preconditioning mechanism. Methods: Isolated Langendorff-perfused rat hearts were subjected to three different studies to determine: Study 1, whether a single intermittent cross-clamp fibrillation episode (10 min) and reperfusion (10 min) before prolonged ischemia acts as a preconditioning trigger for protection; Study 2, whether cardioprotection induced by intermittent cross-clamp fibrillation alone (no prolonged ischemia) involves a preconditioning mechanism; Study 3, whether intermittent cross-clamp fibrillation cardioprotection can be prevented by targeting putative components of the preconditioning mechanism (protein kinase C or the mitochondrial ATP-sensitive potassium (K_ATP) channel). Hearts were reperfused (60 min) and recovery of function (left ventricular developed pressure measured using an intraventricular balloon) and myocardial injury (creatine kinase leakage) were measured. Results: In Study 1, recovery of function in the single intermittent cross-clamp fibrillation hearts was 61 ± 3% (mean ± SEM) (p < 0.05) compared to 41 ± 2% in control group; glibenclamide (a non-specific ATP-sensitive potassium (K_ATP)-channel blocker) prevented this preconditioning protection (37 ± 4%). In Study 2, recovery of function in intermittent cross-clamp fibrillation hearts (62 ± 3%) was significantly (p < 0.05) higher than intermittent cross-clamp fibrillation hearts treated with glibenclamide (33 ± 2%) and ischemia hearts (30 ± 5%). In Study 3, protection by intermittent cross-clamp fibrillation (60 ± 3%; p < 0.05) was attenuated by protein kinase C inhibition (chelerythrine, 34 ± 3%) and mitochondrial K_ATP-channel blockade (5-hydroxydecanoate, 27 ± 4%) to levels not significantly different from that of ischemia hearts (25 ± 4%). Conclusions: The cardioprotective efficacy of intermittent cross-clamp fibrillation was attenuated by protein kinase C inhibition or K_ATP-channel blockade. Involvement of these putative preconditioning cascade components in association with cardioprotection induced by intermittent cross-clamp fibrillation, suggests a role for the ischemic preconditioning mechanism.