SUMMARYLidocaine has proved to be an effective antiarrhythmic agent in the management of ventricular arrhythmias subsequent to acute myocardial infarction. Lidocaine's short duration of action and its propensity for producing central nervous system (CNS) stimulation suggest that a safer and more effective therapeutic agent, based on a modification of the lidocaine structure, might be found. The quaternary ammonium compound, methyl lidocaine, was synthesized and its actions in experimentally-induced arrhythrnias were studied and compared to those of lidocaine. The antiarrhythmic effects of lidocaine and methyl lidocaine were examined in the anesthetized dog against ouabain-induced ventricular tachycardia and in conscious animals with ventricular tachycardia 48 hours after two-stage ligation of the anterior descending coronary artery. Both pharmacological agents were capable of reversing digitalis-induced arrhythmias and restoring normal sinus rhythm in animals 48 hours after surgical ligation of the anterior descending coronary artery, but methyl lidocaine remained effective for a significantly longer period and its continual administration was not associated with signs of CNS toxicity. In experiments designed to determine the electrical fibrillation threshold, both drugs were able to reduce the vulnerability to ventricular fibrillation but the time course of action for each drug differed. Lidocaine had an immediate effect of increasing the ventricular fibrillation threshold whereas the peak effect of methyl lidocaine was delayed and the increase in the fibrillation threshold lasted longer. This study con-

Previous in vitro studies had provided evidence to show that papillary muscles obtained from cats with chronic right ventricular failure had lost their ability to develop a positive inotropic response to glucagon. Since it is difficult to extrapolate from the isolated papillary muscle to the intact heart, studies were done to assess the effects of glucagon in the perfused isovolumically beating heart obtained from cats four months after surgical banding of the pulmonary artery for the experimental production of chronic right ventricular failure (CRVF). At the peak of the dose-response curve, glucagon increased right ventricular isovolumic pressure 25% (39.00 +/- 4.37 to 49.67 +/- 5.15 mm Hg; p less than 0.001) and right ventricular dP/dt 63% (522.2 +/- 93.9 to 852.6 +/- 159.9 mm Hg/sec; p less than 0.001) in 6 normal hearts. Similar dose related increases in right ventricular isovolumic pressure and dP/dt were obtained in 6 hearts taken from cats with chronic right ventricular failure. The respective increases in right ventricular isovolumic pressure and dP/dt were 43% (30.33 +/- 4.01 to 43.67 +/- 6.25 mm Hg; p less than 0.025) and 73% (317.50 +/- 30.29 to 550.83 +/- 89.04 mm Hg/sec; p less than 0.025). These results provide evidence that glucagon possesses the capacity to augment myocardial contractility in the heart with experimentally induced chronic right ventricular failure.