A comparison of no-flow and low-flow ischemia in the rat heart: an energetic study

Abstract

Heat production under no-flow ischemia (ISCH) and under hypoperfusion (HYP) conditions was measured in single isovolumetric contractions of perfused rat ventricles at 25°C. Resting heat production (Hr) and resting pressure decreased when the perfusion rate was reduced from 6 to 1.5 mL·min-1 or lower flows (HYP) and by ISCH. Maximal developed pressure (P) decreased to 29% and 20% of control by HYP at 0.8 mL·min–1 and ISCH, respectively. The tension-independent heat (TIH) fraction attributed to Ca2+-binding, measured during single contractions, decreased under HYP with an increase in the ratio between the maximum relaxation rate and P (–P/P ratio). The TIH fractions (attributed to Ca2+ binding and Ca2+ removal processes) decreased under ISCH. The long duration TIH fraction associated with Ca2+-dependent mitochondrial activity disappeared at flow rates of 1.5 mL·min–1 or lower. The ratio between the tension-dependent energy release and P was decreased by ISCH but not by HYP, indicating that under ISCH there was an improvement in contractile economy, but this was not modified by HYP. Overall, the results indicate that no-flow and low-flow ischemias are energetically different models. While the contractile failure under HYP seems to be related to a decrease in myofilament Ca2+ sensitivity, under ISCH it appears to be related to decreased cytosolic Ca2+ availability combined with a more noticeable effect on a fraction of energy that has been attributed to mitochondrial activity. Furthermore, mechanical and energetic responses of both models (i.e., ISCH and HYP) found in the present work were not the same as those previously observed in severe hypoxia so that all these models should not be used indistinctly.Key words: calorimetry, hypoperfusion, ischemia, muscle economy, tension-dependent heat, tension-independent heat.