MYOCARDIAL STUNNING - ASSOCIATION WITH ALTERED GENE-EXPRESSION

Regional and global myocardial ischemia and reperfusion have been demo nstrated to induce expression of the stress response protein heat shoc k 70 (HSP70) and of immediate early genes, c-jun, c-fos, and c-myc. Be cause of the models that have been utilized, it has not been possible to discriminate whether this response is the consequence of ischemia, reperfusion, or abnormal hemodynamic stress superimposed on stunned my ocardium. In a nonworking isolated and blood-perfused rat heart model, we evaluated the mRNAs for c-fos, c-myc, and hsp70. The heart was sub jected to varying periods of ischemia and reperfusion. Significant inc reases in hsp70 and c-fos were observed, which increased with longer p eriods of ischemia. No significant increase in c-myc was measured. In addition, mRNA encoding the Ca2+/glucose responsive stress protein GRP 78 was evaluated. No increase in this early response gene was noted de spite the use of a model associated with cellular calcium loading. Bas ed on these observations, we suggest that the induction of hsp70 and c -fos is the consequence of ischemia and reperfusion and not dependent upon an early hypertrophy response such as would be observed in afterl oad mismatching or on calcium loading. Further investigations are nece ssary to isolate the effects of ischemia from those of reperfusion.