ISCHEMIC PRECONDITIONING DOES NOT PROTECT AGAINST CONTRACTILE DYSFUNCTION IN THE PRESENCE OF RESIDUAL FLOW - STUDIES IN THE ISOLATED, BLOOD-PERFUSED RAT-HEART

Background We have previously demonstrated that ischemic preconditioni ng (PC) does not protect when oxygen deprivation is accompanied by a h igh level of perfusion (hypoxia). Since clinical ischemia can vary fro m mild to severe, we wished to determine whether PC could protect agai nst injury arising from low-flow ischemia. Methods and Results Functio nal recovery after 30 minutes of reperfusion was assessed in isolated, blood-perfused rat hearts (n=6 per group) subjected to (A) 30 minutes of zero-flow ischemia, (B) 30 minutes of zero-flow ischemia preceded by 3xPC (PC=5 minutes of ischemia+5 minutes of reperfusion), (C) 90 mi nutes of low-flow ischemia at 10% of baseline coronary flow (0.31+/-0. 02 mL/min per gram wet wt), (D) 90 minutes of low-flow ischemia at 10% of baseline coronary flow (0.29+/-0.02 mL/min per gram wet wt) preced ed by 3xPC. PC significantly protected against injury resulting from z ero-flow ischemia (developed pressure recovered to 67+/-6% versus 31+/ -12% in B and A, respectively; P<.05) but not resulting from low-flow ischemia (recovery of developed pressure was 40+/-8% versus 37+/-7% in C and D, respectively). Protein kinase C (PKC) is widely considered t o be involved in the mechanism of PC such that prior activation and tr anslocation of PKC by the PC protocol allows phosphorylation of the en d-effector protein early during the subsequent ischemic insult, before loss of adenosine triphosphate occurs. However, because adenosine tri phosphate content falls slowly during low-flow ischemia, PKC may be ac tivated and translocated early enough to be active during this insult. If so, inhibition of PKC should decrease functional recovery in the c ontrol group. However, functional recovery in control groups was not d ecreased in the presence of the PKC inhibitor polymyxin B (50+/-6%), s uggesting that if activation of PKC occurred during low-flow ischemia, it was not protective. Conclusions PC does not protect against contra ctile dysfunction in the rat when a low level (10% of baseline flow) o f ischemic perfusion remains during the prolonged insult.