A BRIEF PERIOD OF RETROGRADE HYPERTHERMIC PERFUSION ENHANCES MYOCARDIAL PROTECTION FROM GLOBAL-ISCHEMIA - ASSOCIATION WITH ACCUMULATION OF HSP-70 MESSENGER-RNA AND PROTEIN

The induction of heat shock proteins in the myocardium has been sugges ted as a possible intervention to allow for enhanced cardioprotection, We examined the cardioprotective effects of Hsp 70 induction in a cli nically relevant model, in which a brief period of retrograde hyperthe rmic perfusion (42 degrees C) was applied for 15 min, only 5 min prior to global ischemia and reperfusion in the isolated perfused rat heart . Our results indicate that in retrograde hyperthermic perfused hearts (n=17) there was enhanced dP/dT, end diastolic pressure, and peak dev eloped pressure during normothermic reperfusion following 15 min of gl obal ischemia when compared to control hearts perfused at 37 degrees C (n=18). Northern analysis indicated Hsp 70 mRNA, in retrograde hypert hermic perfused hearts, was increased 9.0+/-0./70-fold (P<0.001) by 30 min and 9.1 +/- 0,45-fold (P<0.001) by 60 min of normothermic reperfu sion. Western analysis revealed that the Hsp, heat inducible 72 kD pro tein was increased 1.74 +/- 0.35-fold (P<0.001) by 30 min and 1.79 +/- 0.31-fold at 60 min of normothermic reperfusion when compared to no i schemia hearts. Our results demonstrate that the use of 15 min of retr ograde hyperthermic perfusion, only 5 min prior to global ischemia and reperfusion, provide for enhanced myocardial funtional recovery. Enha nced myocardial functional recovery was associated with the accumulati on of Hsp 70 mRNA and the Hsp 72 kD protein. (C) 1996 Academic Press L imited