Duration and reinstatement of myocardial protection against infarction by ischemic preconditioning in open chest dogs

These studies were undertaken to determine the duration of protection again st myocardial infarction provided by ischemic preconditioning in the canine heart, and to learn if cardioprotection can be restored by another precond itioning stimulus when the initial effect is lost. Control and four precond itioning groups of anesthetized. open-chest dogs were compared. All underwe nt a test 60 min episode of ischemia, induced by occlusion of the anterior descending (LAD) artery. followed by 3 h of reperfusion. Preconditioning wa s induced by one 10 min LAD occlusion, followed by either 10 min, 2, 3, or 5 h of reperfusion. In order to test whether preconditioning could be reins tated. another group of dogs with preconditioning Plus 3 h reperfusion unde rwent a second 10 min preconditioning stimulus with 10 min reperfusion befo re the 60 min test-occlusion. Infarct size (as percent of area-at-risk) was analyzed (using analysis of covariance) with respect to coronary collatera l blood flow measured xvith radioactive microspheres. Infarct size was limi ted markedly by preconditioning (23 +/-6 v 6 +/-2%), P <0.05) but the prote ctive effect was dissipated partially after 2h reperfusion and was dissipat ed completely after 3 h reperfusion (20 +/-4%, non-significant v Control an d significant P <0.05 v preconditioning). Protection was restored in three of six dogs with preconditioning + 5 h repcrfusion, suggesting that the sec ond window of protection appears early in some canine hearts. When precondi tioning was repeated after 3 h reperfusion. cardioprotection was reinstated fully (7 +/-2%, P<0.05 v Control and NS v preconditioning). The results sh ow that maximal preconditioning cardioprotection is present in the dog hear t after 10 min of reperfusion and is dissipated totally following 3 h of re pcrfusion. However. a second preconditioning stimulus of 10 min of ischemia followed by 10 min of reperfusion to the dissipated preconditioned heart r einstates full preconditioning. Thus, this model provides a system to test for theoretical causes of the preconditioned state. Final mediators should be present when preconditioning is present and absent when preconditioning is dissipated. It is noteworthy that a second window of protection appeared in 50% of dogs when the period of reperfusion was extended to 5 h. <(c)> 2 001 Academic Press.