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.