The effects of lidocaine, propranolol, procaine amide, and bretylium tosylate on the contractility of isolated cat papillary muscles.

Abstract

Depression of myocardial contractility by certain anti-arrhythmic agents may be a major clinical hazard to the use of these drugs. In order to study this problem further, cat right ventricular papillary muscles contracting 15 times/min in oxygenated Krebs (25 °C) were exposed to increasing concentrations of lidocaine, propranolol, procaine amide, and bretylium tosylate every 15 min. Measurements of rate of development of tension (dp/dt), peak active tension (AT) and time to peak tension (TPP) were made in the drug-treated muscles and compared to controls. In dosages comparable to human therapeutic levels, only propranolol depressed contractility; dp/dt was decreased 27% at 0.1 μg/ml (p < 0.01). At 10 times the "therapeutic level," lidocaine also depressed contractility; dp/dt was decreased 29% at 100 μg/ml (p < 0.001), and 70% at 200 μg/ml. Bretylium was positively inotropic at this level; at 200 μg/ml, dp/dt was increased 25%. The positive inotropism of bretylium was still seen with cats pretreated with reserpine. Procaine amide unexpectedly produced an increase in dp/dt of 44% at 500 μg/ml (p < 0.01). Reserpine prevented the inotropism of procaine amide. In general AT paralleled dp/dt. TTP was shortened by higher doses of all drugs except propranolol. In summary, lidocaine caused severe depression of contractility at higher doses, propranolol was negatively inotropic, and procaine amide and bretylium were positively inotropic.