Comparison of halothane, enflurane, and isoflurane with nitrous oxide on contractility and oxygen supply and demand in isolated hearts

Abstract

The authors' aim was to examine direct cardiac responses to isoflurane, enflurane and halothane, as altered during mild hypoxia by the substitution of nitrogen (N2) for oxygen (O2), and additionally by the substitution of nitrous oxide (N2O) for N2. Heart rate, atrioventricular conduction time, left ventricular pressure (LVP), peak positive and negative derivatives of LVP (dLVP/dt(max)), coronary flow, O2 delivery (ḊO2), percent O2 extraction, and myocardial O2 consumption (MV̇O2) were examined in 47 isolated guinea pig hearts. Changes in the ratio of ḊO2 to MV̇O2 indicated the relationship of autoregulation of coronary flow to myocardial O2 utilization. Each heart was first exposed to 96% O2 and then randomly exposed to 48% N2 and 48% N2O alone and with three equivalent concentrations of one of three volatile anesthetics: isoflurane (n = 15), halothane (n = 16), or enflurane (n = 16). Results were as follows: 1) N2 alone significantly decreased LVP, +dLVP/dt(max) and -dLVP/dt(max), ḊO2, and MV̇O2; increased coronary flow; and produced no change in heart rate, atrioventricular conduction time, percent O2 extraction, or the ḊO2/MV̇O2 ratio. 2) Compared to N2, N2O alone only produced additional significant decreases in LVP and +dLVP/dt(max). 3) In the presence of N2 or N2O, each volatile anesthetic caused significant stepwise decreases in heart rate, LVP, +dLVP/dt(max) and -dLVP/dt(max), MV̇O2, and percent O2 extraction; no additional change in coronary flow or ḊO2; and a stepwise increase in the ḊO2/MV̇O2 ratio. The effects of halothane and enflurane were generally greater than those of isoflurane. 4) Each volatile anesthetic caused an additive, parallel depression of LVP and percent O2 extraction as a function of MAC with N2O compared to N2. This study demonstrates that the direct negative inotropic effects of halothane and enflurane are more pronounced than those of isoflurane and are accompanied by a greater reduction in O2 utilization by halothane and enflurane than by isoflurane in the presence of mild hypoxia alone or with the addition of N2O. The study also demonstrates that N2O accentuates the negative inotropic effects of volatile anesthetics during reduced O2.