Comparison of the In Vitro Myocardial Depressant Effects of Isoflurane and Halothane Anesthesia

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Abstract
The myocardial depressant effects effects of isoflurance and halothane were compared using feline right ventricular papillary muscles bathed in Krebs-bicarbonate solution. In experiment 1 muscles were stimulated by field electrodes (0.2 Hz) to obtain control measurements of developed tension (dt) and maximal rate of tension development (dF/dt) prior to exposing the papillary muscles to four concentrations of either isoflurane (4.0%, 2.0%, 1.0%, 0.5%) or halothane (2.0%, 1.0%, 0.5%, 0.25%). Repeat measurements of dt and dF/dt were recorded after 20 min at each concentration. Isoflurance and halothane both caused dose-dependent depression of dt and dF/dt, but at 0.5%, 1.0%, and 2.0%, halothane was significantly more depressant than isoflurance (P < 0.01 for dt and dF/dt). Quadratic equations were fitted to the dose-response data by least squares analysis (R2 > .985 for both anesthetics), and the isoflurance and halothane concentrations that decreased dt to 90%, 70%, 50%, and 30% of control were determined to compare the relative myocardial depressant potency of isoflurance and halothane by linear regression analysis. This potency relationship is described by the equation: isoflurance concentration = -0.005 + 1.445 (halothane concentration). In experiment 2 papillary muscle responses at two similar cardiodepressant concentrations of isoflurance (1.25% and 2.0%) or halothane (0.80% and 1.35%) were compared at stimulus frequencies of 0.05, 0.1, 0.2, 0.4, 0.8, 1.0, and 2.0 Hz. The concentration of isoflurance and halothane were selected from the data obtained in experiment 1 and represent the anesthetic concentrations that diminish muscle function to approximately 70% and 50% of control. After control measurements of dt were obtained at all stimulus frequencies, the muscles were exposed to either isoflurance or halothane for 20 min. Repeat measurements of dt at the different stimulus rates were obtained. At lower stimulation rates (range, 0.05-1.0 Hz) halothane and isoflurane caused comparable depression of dt, but both anesthetics demonstrated some degree of frequency dependence in that their depressant effects diminished as muscle stimulation rates increased. However, at high muscle stimulation rates (2.0 Hz) isoflurance was significantly less depressant than halothane (P < 0.001). The observed frequency dependence of both halothane and isoflurane suggest that the negative inotropic effects of both agents may involve inhibition of extracellular Ca2+ influx; however, the depressant effect is isoflurane are more effectively attenuated by stimulus conditions that enhance extracellular Ca2+ influx when muscle stimulation rates approach the physiologic range.