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Quinidine syncope is an unpredictable side effect of quinidine administrateion which has a mortality rate of 11.5 per cent when managed with conventional drugs and direct-current countershock. In 2 patients with quindine syncope, the arrhythmias were effectively controlled within 30 minutes following the slow infusion of 150 mg. of bretylium tosylate. This control is contrasted with 2 cases managed in the conventional manner. Bretylium tosylate is a quaternary amine with unique antifibrillatory properties and appears to have a significant role in the management of these arrhylmias.

Combining propranolol and quinidine should improve the antiarrhythmic action of quinidine by blocking beta adrenergic receptors, an action helpful in cases of arrhythmias associated with anesthetic agents, digitalis and stress. To test this hypothesis, 60 patients with paroxysmal arrhythmias resistant to quinidine and 17 with chronic atrial fibrillation were given propranolol alone or in combination with quinidine (or procainamide) and followed up 1 to 17 months. Patients with severe aortic valve disease, severe mitral insufficiency, acute myocardial infarction or obstructive airway diseases were excluded from this study. The condition of 13 of 19 patients with paroxysmal atrial or nodal tachycardia was improved. In paroxysmal ventricular tachycardia combined therapy or propranolol alone was effective in 11 of 14 patients. Paroxysmal atrial flutter or fibrillation was suppressed in 11 of 16 patients, with a 75 percent or greater reduction in attacks. Prophylaxis of chronic atrial fibrillation terminated by drugs or by electroshock was effective in 9 of 11 patients (15 trials) followed up for 7 months. Sustained atrial fibrillation was terminated with propranolol, 40 to 160 mg, and quinidine sulfate, 1.2 to 1.6 g/day, in 41 percent of patients, a result no better than with propranolol alone. Propranolol slowed the ventricular rate in normal sinus rhythm as well as in atrial fibrillation and flutter. Significant slowing, although it was less in magnitude, occurred with the combination of propranolol and quinidine. It is concluded that propranolol potentiates quinidine and allows effective prophylaxis of atrial, nodal and ventricular arrhythmias in quinidine-resistant patients. Diarrhea was the only side effect peculiar to the combination of drugs.

Digitalis accelerated the rate in atrial flutter resulting in atrial fibrillation, whereas the addition of quinidine slowed the atrial rate producing either asystole or interference dissociation. In some patients receiving both digitalis and quinidine, the atrial rate showed less of a tendency to slow or actually increased, resulting in atrial fibrillation followed by normal sinus rhythm. This suggests an overriding effect of digitalis. Since the spontaneous termination of atrial flutter occurred in unknown circumstances that usually slowed the atrial rate and asystole was observed, this suggests that asystole is not a toxic effect of quinidine. Atrial flutter, fibrillation, and atrial premature beats began more commonly in the P-T cycle than in the T-P cycle. Since atrial recovery is more likely incomplete during the P-T cycle, this favors reentry as the underlying mechanism in the patient studied. Atrial and nodal tachycardia begin with an irregular sequence of premature beats before a stable tachycardia is established. There is usually a significant slowing of the rate prior to termination of the abnormal rhythm. Sinus arrest with ventricular escape is the usual method of termination, regardless of the form of therapy used. Bursts of rapid ventricular rhythm resembling ventricular tachycardia were seen only after the use of pressor agents. Atrial tachycardia with block treated with digitalis shows an initial atrial slowing but, as the dose of digitalis was raised in one patient, abrupt increases in atrial rate occurred until the rhythm terminated. This is a mechanism similar to that seen in the digitalis-induced termination of atrial flutter.

Study of the cardiovascular effects of glucagon in man have shown a positive inotropic and chronotropic effect resulting in an increase in cardiac output.1-3 These effects occur one to 3 minutes after the intravenous injection of 3 to 5 mg. of glucagon and are dissipated in 30 minutes. These effects are similar to those of isoproterenol; however, glucagon has a limited chronotropic effect in man’ and has not caused arrhythmias even in the presence of digitalis.2 In contrast, a recent study of patients with chronic valvufar heart disease concluded that these cardiac effects were variable, not dose-related, and of small magnitude when present.4 In addition to these cardiac effects, glucagon has been shown to increase renal excretion of water and electrolytes.6 Since previous studies are limited to the observation of the effects of a single bolus injection, given to patients who were not in stress situations, it seemed appropriate to study the feasibility and efficacy of a continuous infusion of glucagon over a period of days in the treatment of conditions with low cardiac output or cardiogenic shock. Methods

The evidence has been reviewed which suggests that the upstroke of the action potential in heart muscle is due to the entry of sodium ions. This conclusion is based on the failure of the upstroke to occur if 90 per cent of the sodium is replaced by sucrose, and the demonstration of a reduction in amplitude of the rising phase of the action potential with each decrement in extracellular sodium concentration or an increase in amplitude with increasing extracellular sodium concentration. In addition, the demonstration of a change in membrane resistance of one-hundred-fold at the time of the rising phase suggests increased permeability of the membrane at this time. The voltage-clamp studies in the squid giant axon clearly show an inward movement of current during the rising phase, which disappears when choline replaces sodium in the perfusing bath. The resting membrane potential resembles the model of a potassium and chloride concentration cell, since calculations based on measured concentrations across the membrane agree fairly closely with measured potentials. Furthermore, the membrane resting potential is altered in a predictable manner by changed extracellular potassium and chloride concentration, but is not appreciably affected by changing sodium concentration. Since the skeletal muscle membrane appears to be freely permeable to chloride, and only sparingly so to potassium, and since potassium permeability is selectively altered during the electrical cycle, the chloride ionic concentration gradient is probably dependent on the transmembrane potential, and, therefore, is passive. The current carried by the chloride ion in cardiac fibers is small. Little is known of the factors which alter membrane permeability or affect the transfer rates during recovery, but it is apparent that sodium is removed from the cell after the rising phase and is replaced by potassium to restore membrane resting potential.

Propagated wavefronts were produced by mechanical stimulation at points located deeply within the myocardium, and the external field so produced was measured by electrodes located within a radius of 10 mm. from the centrally stimulated point. In 104 experiments in 10 dogs the external field so produced was negligible until propagation reached either the epicardial or endocardial surfaces. If it is assumed that propagated intramural activity is temporarily a closed electromotive surface, then the data presented suggest that there is a uniform difference in potential across this surface. Since there is no fundamental difference in the wavefront characteristics of closed electromotive surfaces and those which present boundaries on the epicardial or endocardial surfaces, these data strongly suggest that there is a uniform difference in potential across all propagated wavefronts in normal ventricular muscle.