Inhibition of protein synthesis does not block myocardial protection afforded by preconditioning

It is currently unknown how preconditioning the heart with brief periods of ischemia makes it resistant to infarction from a subsequent ischemic insult. The protein synthesis inhibitors, cycloheximide and actinomycin D, were used to determine whether preconditioning involves synthesis of a protective protein. Ischemia was produced by occlusion of a branch of the left coronary artery in open-chest anesthetized rabbits. All groups were subjected to 30 min of ischemia followed by 3 h of reperfusion. The first two groups served as noninhibited controls. Group 1 was subjected to ischemia with no preconditioning. Group 2 was preconditioned with two 5-min ischemic periods each followed by 10 min of reperfusion, before the 30-min ischemic period. Groups 3 and 4 were the same as groups 1 and 2, respectively, except that cycloheximide was administered before coronary occlusion. Groups 5 and 6 were also the same as groups 1 and 2 except that actinomycin D was administered before coronary occlusion. After 3 h of reperfusion all hearts were removed and the size of the ischemic zone and infarct were determined. The percent of the ischemic zone infarcted was small and similar in all preconditioned groups (3.3 +/- 1.1% for group 2, 7.4 +/- 3.3% for group 4, and 0.5 +/- 0.7% for group 6). All nonpreconditioned groups had large infarcts with no differences between groups (39.0 +/- 8.5% for group 1, 31.6 +/- 6.3% for group 3, 30.8 +/- 5.9% for group 5). Because neither cycloheximide nor actinomycin D could block protection afforded by preconditioning, it seems unlikely that synthesis of a protective protein is the mechanism of protection.