Myocardial heat shock gene expression in pigs is dependent on superoxide anion generated at reperfusion

The heat shock response is a conserved response to cell injury. We sought to determine if ischemia alone versus events at reperfusion stimulated expression of the major heat shock protein (hsp-72) in a clinically relevant model of global myocardial ischemia in pigs. Pigs were placed on nonpulsatile car-diopulmonary bypass. Serial transmural cardiac biopsies were taken at baseline following 20 min of nor-mothermic global ischemia (induced by crossclamping the aorta) and at 20, 40, and 60 min of reperfusion. Test animals received a bolus and subsequent aortic root infusion of superoxide dismutase (total 7,500 U/kg) beginning just prior to reperfusion. Hsp-72 mRNA abundance was estimated from Northern blots. We found that hsp-72 mRNA was not induced following 20 min of ischemia but accumulated to high levels within 20 min of reperfusion. Intravascular administration of superoxide dismutase at reperfusion eliminated hsp-72 mRNA induction. We conclude that in the postischemic myocardium, hsp-72 gene expression is dependent on superoxide anion generation at reperfusion. In this setting, hsp-72 gene expression may reflect a specific response to oxidative injury rather than a more general response to metabolic stress associated with ischemia.