INFLUENCE OF HEAT-STRESS ON MYOCARDIAL-METABOLISM AND FUNCTIONAL RECOVERY AFTER CARDIOPLEGIC ARREST - A P-31 NMR-STUDY

Objective: Heat stress and induction of heat shock proteins confer pro tection against myocardial ischemia-reperfusion injury; however the pr ecise mechanisms of this effect remain unknown. We investigated the in fluence of heat stress on metabolic and functional recovery after card ioplegic arrest, in a protocol mimicking clinical donor heart preserva tion. Methods: Langendorff perfused rat hearts in control group (C, n = 6) and heat stressed (24 h prior to experiment) group (HS, n = 6) we re subjected to 4 h of ischemia at 4 degrees C following cardioplegic arrest (St. Thomas' No. 1). P-31 nuclear magnetic resonance spectrosco py was used to follow changes in ATP, phosphocreatine and inorganic ph osphate concentrations during the pre-ischemic, ischemic and reperfusi on periods. Myocardial adenine nucleotide levels in hearts at the end of experiments and purine catabolite release in coronary effluent duri ng reperfusion, were evaluated using high performance liquid chromatog raphy. Mechanical function in the pre-ischemic and reperfusion periods was evaluated using an intraventricular balloon. Western immunoblotti ng was used to quantitate HSP70 expression. Results: Although baseline concentrations of ATP and phosphocreatine were similar in C and HS gr oups, the rate of high-energy phosphate depletion was attenuated durin g the early phase of ischemia in HS groups. On reperfusion, recovery o f ATP was 10-20% greater in HS versus C groups; phosphocreatine levels also recovered better in the HS group, transiently reaching levels 40 % higher in HS versus C groups. The concentrations of adenine nucleoti des in hearts were significantly higher in the HS versus C groups. The se changes were associated with an attenuation of total purine catabol ite release in the coronary effluent in HS versus C groups. A signific ant improvement in relative recovery of developed pressure was shown i n HS versus C groups in the post-ischemic periods. Conclusions: Heat s tress causes beneficial changes in high-energy phosphate metabolism in the rat heart subjected to cardioplegic arrest and ischemia. Improved mechanical recovery in HS versus C groups was associated with a decre ased rate of high-energy phosphate depletion and increased recovery of ATP and phosphocreatine levels during reperfusion. Changes in energy metabolism may play a role in the mechanism of cardioprotection by hea t stress during prolonged hypothermic cardiac arrest. (C) 1998 Elsevie r Science B.V. All rights reserved.