Effects of hypothermia on myocardial substrate selection

Background. Hypothermia lowers the metabolic rate and increases ischemic tolerance but the effects of temperature on myocardial substrate selection are not well defined. Methods. Isolated rat hearts were perfused with physiologic concentrations of ¹³C labeled lactate, pyruvate, acetoacetate, mixed long-chain fatty acids, and glucose. Hearts were cooled over 5 to 10 minutes to one of four target temperatures (37°, 32°, 27°, or 17°C), then perfused for an additional 30 minutes, freeze-clamped, and extracted. ¹³C NMR spectra were obtained and substrate oxidation patterns were determined by isotopomer analysis. Results. Although hearts in all groups were supplied with identical substrates, the percentage of acetyl-CoA oxidized within the citric acid cycle that arose from fatty acids decreased significantly from 53.8% ± 0.8% in the 37°C group to 33.1% ± 3.3% in the 17°C group. Lactate or pyruvate utilization increased from 3.3% ± 0.5% to 25.7% ± 3.6%, respectively (p < 0.05 by one-way ANOVA). Conclusions. These data suggest that moderate hypothermia suppresses fatty acid oxidation and deep hypothermia significantly increases utilization of lactate and pyruvate. These effects may result from relative inhibition of catabolism of complex molecules such as fatty acids, or stimulation of pyruvate dehydrogenase. These effects on substrate metabolism may play a role in myocardial protection afforded by hypothermia.