Halothane and the beating response and ATP turnover rate of heart cells in tissue culture.

The effects of halothane on the beating response of rat heart cells in tissue culture were studied using an optical-electronic monitoring device. A dose-response curve was obtained over a concentration range to as much as 5 vol per cent halothane. The clinical dosage of 1 vol per cent halothane decreased the inotropic response of 4-10-day-old cells to 59 plus or minus 10 per cent of the original beating strength; no significant decrease in beating strength was seen in 25-30-day-old cells. One volume per cent halothane caused no significant change in the chronotropic response of the heart cells. Higher concentrations of halothane caused significant negative chronotropic and negative inotropic responses in a dose-related manner. When glycolysis was inhibited by 2-deoxyglucose in the growth medium, the cells became dependent on fatty-acid oxidation and oxidative phorphorylation for energy and showed increased sensitivity to halothane; for example, the chronotropic response to 5-8-day old cells treated with 2-deoxyglucose was decreased approximately 70 per cent by exposure to 3 vol per cent halothane, whereas 4-10-day-old cells maintained on a complete growth medium showed only a 40 per cent decrease. Increasing concentrations of halothane decreased the rate of ATP turnover. This supports evidence suggesting that halothane blocks electron transport in the NADH-coenzyme Q reductase level. The model described provides a means for determining anesthetic potency in a mammalian system in terms of functional as well as metabolic responses. It also provides a means for study of metabolic effects of anesthetics and other drugs.