Heat-shock protein induction in rat hearts. A direct correlation between the amount of heat-shock protein induced and the degree of myocardial protection.

Abstract

BACKGROUND Previous studies have demonstrated that heat-shock treatment results in the induction of 72-kD heat-shock protein (HSP72) and a reduction of infarct size after subsequent ischemia and reperfusion. METHODS AND RESULTS To test the hypothesis that the degree of protection from ischemic injury in heat-shocked rats correlates with the degree of prior HSP72 induction, rats pretreated with 40 degrees C, 41 degrees C, or 42 degrees C of whole-body hyperthermia followed by 24 hours of recovery and control rats (n = 6 in each group) were quantitatively assessed for the presence of myocardial HPS72 by optical densitometry of Western blots and a primary antibody that is specific for HSP72 and a tertiary antibody labeled with 125I. Although rats heat-shocked to 40 degrees C had no significant induction of myocardial HSP72, rats heat-shocked to 41 degrees C and 42 degrees C demonstrated progressively increased amounts of myocardial HSP72 compared with controls. Separate groups of rats heat-shocked to 40 degrees C (n = 16), 41 degrees C (n = 37), and 42 degrees C (n = 36) with 24 hours of recovery and controls (n = 26) were subjected to 35 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Compared with control and 40 degrees C rats, there was progressive infarct size reduction, assessed by triphenyltetrazolium chloride staining, in rats that were heat-shocked to 41 degrees C and 42 degrees C. Furthermore, there was a direct correlation between the amount of HSP72 induced and the reduction in infarct size (r = .97, P = .037). CONCLUSIONS These results suggest that the improved salvage after heat-shock pretreatment may be related to the amount of HSP72 induced before prolonged ischemia and reperfusion.