Heat acclimation-induced elevated glycogen, glycolysis, and low thyroxine improve heart ischemic tolerance

Based on our observations of energy sparing in heat-acclimated (AC) rat hearts, we investigated whether changes in preischemic glycogen level, glycolytic rate, and plasma thyroxine level mediate cardioprotection induced in these hearts during ischemia-reperfusion insults. Control (C) (24°C), AC (34°C, 30 days), acclimated-euthyroid (34°C + 3 ng/ml L-thyroxine), and control hypothyroid (24°C + 0.02% 6-n-propyl-2-thiouracil) groups were studied. Preischemic glycogen was higher in AC than in C hearts [39.0 ± 8.5 vs. 19.2 ± 4.2 (SE) μmol glucose/g wet wt; P < 0.0006], and the lactate produced vs. glycogen level during total ischemia (¹³C-NMR spectroscopy) was markedly slower (AC: -0.82x, r = 0.98 vs. C: -4.7x, r = 0.9). Time to onset of ischemic contracture was lengthened, and the fraction of hearts experiencing ischemic contracture was lowered. Pulse pressure recovery was improved in AC compared with C animals before, but not after, absolute sodium iodoacetate-induced glycolysis inhibition. Acclimated-euthyroid hearts exhibited decreased ischemic tolerance, whereas induced hypothyroidism in C improved cardiotolerance. Thus higher preischemic glycogen and slowed glycolysis are associated with hypothyroidism and are likely important mediators of the improved ischemic tolerance exhibited by AC hearts.