Heat stress and induction of heat shock proteins confer protection against myocardial ischemia-reperfusion injury; however the precise mechanisms of this effect remain unknown. We investigated the influence of heat stress on metabolic and functional recovery after cardioplegic arrest, in a protocol mimicking clinical donor heart preservation.Methods:
Langendorff perfused rat hearts in control group (C, n=6) and heat stressed (24 h prior to experiment) group (HS, n=6) were subjected to 4 h of ischemia at 4°C following cardioplegic arrest (St. Thomas' No. 1). 31P nuclear magnetic resonance spectroscopy was used to follow changes in ATP, phosphocreatine and inorganic phosphate concentrations during the pre-ischemic, ischemic and reperfusion periods. Myocardial adenine nucleotide levels in hearts at the end of experiments and purine catabolite release in coronary effluent during reperfusion, were evaluated using high performance liquid chromatography. Mechanical function in the pre-ischemic and reperfusion periods was evaluated using an intraventricular balloon. Western immunoblotting was used to quantitate HSP70 expression.Results:
Although baseline concentrations of ATP and phosphocreatine were similar in C and HS groups, the rate of high-energy phosphate depletion was attenuated during the early phase of ischemia in HS groups. On reperfusion, recovery of 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 nucleotides in hearts were significantly higher in the HS versus C groups. These changes were associated with an attenuation of total purine catabolite release in the coronary effluent in HS versus C groups. A significant improvement in relative recovery of developed pressure was shown in HS versus C groups in the post-ischemic periods.Conclusions:
Heat stress 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 decreased 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 heat stress during prolonged hypothermic cardiac arrest.