GLOBAL MYOCARDIAL-ISCHEMIA PROTECTS THE MYOCARDIUM FROM SUBSEQUENT REGIONAL ISCHEMIA

Many investigators use in vitro models of global ischemia to examine t he effects of preconditioning, often with recovery of contractile func tion as the end-point. Such models are relevant to myocardial protecti on during cardiac surgery. However, there is still debate as to whethe r preconditioning preserves ventricular contraction secondary to limit ation of infarction or by a direct effect on stunning. Since infarct s ize is the original end-point against which protection by precondition ing is measured, our aims were, first, to validate global ischemic pre conditioning by measuring infarct size after subsequent regional ische mia and, second, to correlate limitation of infarct size with mechanic al function. After stabilization, seven isolated buffer perfused rabbi t hearts were subjected to 5 minutes of global ''no-flow'' ischemia fo llowed by 10 minutes of reperfusion (''global preconditioning''). Seve n control hearts were allowed to stabilize for an additional 15 minute s at constant flow. Subsequently, regional ischemia was induced in bot h groups for 45 minutes followed by 2 hours of reperfusion. Left ventr icular and coronary perfusion pressures were measured throughout. Myoc ardial infarct size was measured using triphenyltetrazolium staining a nd expressed as a percentage of the area at risk outlined with fluores cent microspheres. The ratio of infarct to risk zone was reduced from 47.6 +/- 7.3% in control hearts to 16.4 +/- 5.4% (p=0.005) in precondi tioned hearts, confirming the efficacy of global preconditioning. In a ddition, preconditioning led to a better preservation of systolic func tion, which correlated significantly with limitation of infarct size ( r=0.75, p=0.002). Global preconditioning may account for the successfu l use of cross-clamp fibrillation during cardiac surgery.