DIRECT COMPARATIVE EFFECTS OF HALOTHANE, ENFLURANE, AND ISOFLURANE ON OXYGEN-SUPPLY AND DEMAND IN ISOLATED HEARTS

The authors examined the direct myocardial and coronary vascular responses to isoflurane, enflurane, and halothane and compared their effects on attenuating autoregulation of coronary flow (CF) as assessed by changes in the O2 supply-demand relationship. The effects of these anesthetics on left ventricular pressure (LVP), CF, percentage of O2 extraction, O2 delivery (D(o2)), and mycardial O2 consumption (MVo2) were examined in 47 isolated guinea pig hearts perfused at constant pressure. An increase in D(o2) from control relative to MV(o2) was used to indicate attenuation of autoregulation, and a decrease in MV(o2) relative to D(o2) to indicate a reduction of myocardial work and O2 utilization. Each heart was exposed to 0.51, 0.70, and 1.20 vol% halothane (n = 16); 0.91, 1.41, and 2.04 vol% enflurane (n = 16); or 0.45, 0.87, and 1.22 vol% isoflurane (n = 15). Adenosine (2 mM) was given to test maximal CF in arrested and in paced hearts. Mean results for increasing concentrations of each agent were as follows: LVP (average control 92 +/- 5 mmHg) (standard error of mean [SEM]) decreased by 15%,* 25%,* and 34%* with halothane; 13%,* 24%,* and 34%* with enflurane; and only 3%, 7%, and 13%* with isoflurane (*P < 0.05 vs. controls). CF (control 6.1 +/- 0.3 ml.min-1.g-1) was not altered significantly with halothane or enflurane but increased by 6%, 9%, and 16%* with isoflurane and maximally by 86 +/- 7%* with adenosine. The percentage of O2 extraction (control 69.2 +/- 1.8%) decreased by 9%,* 16%,* and 22%* with halothane; 7%,* 15%,* and 22%* with enflurane; and only 1%, 4%, and 7%* with isoflurane. MV(o2) (control 59 +/- 3-mu-l.min-1.g-1) decreased by 0%, 7%, and 14% with halothane and 4%, 9%,* and 17%* with enflurane, but was unchanged with isoflurane. The ratio of D(o2) to MV(o2) increased by 9%,* 17%,* and 22%* with halothane; 8%,* 16%,* and 23%* with enflurane; and only 1%, 3%, and 8%* with isoflurane. In this model, the findings show that isoflurane only slightly increases CF and D(o2), with no change in MV(o2) whereas halothane and enflurane do not increase CF or D(o2) but moderately decrease MV(o2), so that the ratio of D(o2) to MV(02) increase is significantly larger with halothane and enflurane than with isoflurane. This indicates that the greater direct negative inotropic effects of halothane and enflurane, compared with isoflurane, are associated with a lesser attenuation of coronary autoregulation, but with a larger reduction in O2 utilization.