STRETCH PRECONDITIONS CANINE MYOCARDIUM

Preconditioning is believed to be directly triggered by brief ischemia-reperfusion. However, brief ischemia results in transient dilation (or stretching) of the heart. We therefore sought to determine whether stretch per se, induced by rapid volume overload instead of brief coronary occlusion, could precondition the heart via stretch-activated ion channels. Forty-two anesthetized dogs underwent 1 h of coronary artery occlusion followed by 4.5 h of reperfusion. Before this, each dog underwent either no intervention (control) or acute volume overload. In three additional groups, Gd3+, a potent blocker of stretch-activated channels was injected as a bolus into the left atrium of each dog at the onset of the treatment period. Then the dogs underwent either acute volume overload, a 5-min episode of coronary occlusion followed by 10 min of reperfusion, or no intervention. Myocardial stretch significantly reduced infarct size after a subsequent 60-min ischemic insult. Protection afforded by stretch was completely prevented by Gd3+. Reduction in infarct size afforded by ischemic preconditioning was partially reversed by Gd3+. Gd3+ per se did not, however, alter the extent of necrosis. The present study suggests that myocardial stretch per se can precondition the canine heart, probably by activation of stretch-activated ion channels.