Use of heart cell cultures as a tool for the evaluation of halothane arrhythmia

The effects of various combinations of epinephrine-halothane and epinephrine-enflurane were tested on beating myocardial muscle cells cultured from 2- to 3-day-old rats. A series of culture plates containing myocytes were exposed to 0.5, 1.0, 1.5, and 2% halothane. At each halothane concentration, 9 ng of epinephrine was added, and the rate of contraction and rhythm of myocytes were observed. With increasing halothane concentrations, a significant and progressive increase in the percentage of plates demonstrating arrhythmia was observed. In a separate series of experiments, doses of epinephrine were added following exposure to 1.5% halothane. As the dose of epinephrine was increased progressively more plates displayed arrhythmia. In addition, culture plates were exposed to enflurane (3 and 6%), and epinephrine was added to each plate. No arrhythmia was observed in any of the 3% enflurane exposed plates. However at 6%, 100% of the plates displayed arrhythmia. In another series of experiments the efficaciousness of quinidine, procaine amide, lidocaine, propranolol, and verapamil in converting cell culture arrhythmia to normal rhythm following epinephrine and halothane was tested. Quinidine converted 96% of all arrhythmic plates to normal rhythm, procaine amide 80%, lidocaine 50%, and propranolol 10%. Verapamil failed to convert any arrhythmic plates to normal rhythm. It was concluded from this study that halothane directly "sensitizes" heart cells in tissue culture, and that the "sensitization" process is a linear, dose-dependent phenomenon.