MYOCARDIAL SELF-PRESERVATION - ABSENCE OF HEAT-SHOCK FACTOR ACTIVATION AND HEAT-SHOCK PROTEIN-70 MESSENGER-RNA ACCUMULATION IN THE HUMAN HEART DURING CARDIAC-SURGERY

Following myocardial ischemia, heat shock proteins (HSPs) have been fo und to be associated with a reduction in infarct size and enhanced pos tischemic functional recovery. Stress-induced regulation of the HSPs i s mediated by the activation and binding of the heat shock transcripti on factor (HSF) to a specific DNA sequence located in front of all HSP genes, known as the heat shock element (HSE). To determine whether HS Ps were induced in the human heart following the ischemic stress exper ienced during cardiac surgery, biopsies were performed of the right at rium at three sequential times: prior to establishing cardiopulmonary bypass; immediately after aortic declamping; and following termination of bypass. These samples from the atria of patients undergoing corona ry bypass surgery were assessed for HSF activation using mobility shif t gels, and analyzed for HSP 72 mRNA by Northern blot. Although a high level of the HSP 72 protein was noted at all intervals, no HSF activa tion was detected, nor was an accumulation of HSP 72 mRNA observed at any time during surgery. These data suggest that HSPs are not induced during cardiac surgery and that the high ''constitutive'' level of the HSP 72 protein detected in these hearts may not be secondary to an HS F-HSE interaction, but rather, the result of other transcription facto rs acting at alternative regions of the HSP 70 promoter.