One-day hypothermic preservation of isolated hearts with halothane improves cardiac function better than low calcium

Abstract

Background: Halothane exerts a potent negative inotropic effect on the heart and mimics many of the cardiac effects of lowered extracellular CaCl2. Reduced slow inward Ca2+ current and sarcoplasmic reticular effects on intracellular Ca2+ are likely involved. The authors reported previously that halothane protects against hypoxic and ischemia reperfusion injury in isolated hearts. The aim of this isolated heart study was to compare protective effects of halothane and low CaCl2 (0.5 mM) administered during 1 day of hypothermic perfusion on return of normothermic perfusion.

Methods: Guinea pig hearts (n = 66) were isolated and perfused at 37 degrees C with a Krebs' solution, gassed with 96% O2, 4% CO2, and containing 2.5 mM Ca2+, and 4.5 mM K+. Heart rate, isovolumetric left ventricular pressure, coronary flow, %O2 extraction, O2 consumption rate, and relative cardiac efficiency (EFF = heart rate.left ventricular pressure/O2 consumption rate) were measured in five groups of hearts: time controls (no hypothermia); 1.5, and 3% halothane delivered by vaporizer; cold controls (hypothermia only); and 0.5 mM CaCl2. Halothane was administered, or CaCl2 was decreased 0.5 h before hypothermia at 3.8 +/- 0.1 degrees C, during hypothermia for 22 h, and for 0.5 h after rewarming to 37.0 +/- 0.1 degrees C. Hearts were perfused at 25% of initial coronary flow during hypothermia.

Results: All groups had similar ventricular function and vasodilator responses before hypothermia. During normothermic reperfusion after hypothermia, both concentrations of halothane protected better than low CaCl2. Values, expressed as a percent of initial values in the five groups (time control, 3% halothane, 1.5% halothane, cold control, and 0.5 mM CaCl2, were respectively: 90 +/- 6, 54 +/- 6*, 48 +/- 5*, 27 +/- 8, 27 +/- 4% for left ventricular pressure; 84 +/- 5, 61 +/- 4*, 62 +/- 6*, 40 +/- 5, 34 +/- 5% for EFF; and 102 +/- 3, 63 +/- 3*, 66 +/- 3*, 55 +/- 2, 42 +/- 2% for coronary flow (*P < 0.05 halothane vs. 0.5 mM CaCl2). The coronary flow response to endothelium-dependent (acetylcholine) and endothelium-independent (nitroprusside) vasodilators was also greater after halothane than after 0.5 mM CaCl2.

Conclusions: Halothane administered during hypothermia restores left ventricular pressure, cardiac efficiency, basal coronary flow, and flow responses better than low CaCl2. Although halothane and low CaCl2 both reduce intracellular Ca2+, contractile force, and metabolic demand, the better protective effect of halothane is not likely simply due to a reduction in contractile function and metabolic rate before or initially after hypothermia because these were reduced much more by low CaCl2 than by halothane.