Helfant, Lau, Cohen and Damato, Circulation (1967),158 studied the effects of intravenous PHT on atrioventricular conduction in fourteen patients at constant heart rates in digitalized and nondigitalized states. In both groups, PHT was found to decrease P-R interval with the changes highly significant (p<0.001). It was suggested that when digitalis excess is manifested by both ectopia and incomplete heart block, PHT would have special utility. In contrast to the commonly used antiarrhythmic agents, PHT enhances A-V conduction in addition to suppressing ectopia.

158. Helfant, R. H., Lau, S. H., Cohen, S. I., and Damato, A. N., Effects of diphenylhydantoin on atrioventricular conduction in man, Circulation, 36: 686-691, 1967.

Damato, Berkowitz, Patton and Lau, American Heart Journal (1970), 935 in thirteen patients, showed that PHT enhanced atrioventricular conduction (i.e., shortened the P-H interval) over various paced heart rates. Also PHT did not prolong intraventricular conduction as measured by H-Q interval. These observations were made while studying His-bundle activity with an electrode catheter technique.

935. Damato, A. N., Berkowitz, W. D., Patton, R. D., and Lau, S. H., The effect of diphenylhydantoin on atrioventricular and intraventricular conduction in man, Amer. Heart J., 79: 51-56, 1970.

Reimann, Lemmel and Theisen, Munchener Medizinische Wochenschrift (1971),1450 found that, in forty-seven of fifty patients, PHT eliminated extrasystoles and tachycardias of both atrial and ventricular origin. They noted that A-V conduction was not delayed. Intravenous PHT, 125-375 mg, was usually promptly effective.

1450. Reimann, R., Lemmel, W., and Theisen, K., Efficacy and risks of diphenylhydantoin in cardiac arrhythmias, Munchen Med. Wschr., 113: 893-899, 1971.

Benaim, Chapelle and Chiche, Annales de Cardiologie et D’Angeiologie (1972), 816 reported fifteen patients with arrhythmias, who were injected with doses of 5 to 10 mg/kg of PHT. Recordings of the His-potential achieved during the therapeutic test showed that PHT does not usually alter the frequency of the sinus node; and it definitely improves atrioventricular conduction. In fact, a shortening of the P-H interval was obtained eight times out of eleven in conducted sinus rhythms. In most cases it did not after intraventricular conduction: H-V remained constant eleven times out of fifteen. In four cases, a depression in intraventricular conduction was noted with a lengthening of the H-V interval. In conclusion, the authors emphasize how valuable PHT is in arrhythmias accompanied by atrioventricular conduction defects.

816. Benaim, R., Chapelle, M., and Chiche, P., Action of diphenylhydantoin on atrioventricular and intraventricular conduction in humans, Ann. Cardiol. Angeiol., 21: 379-388, 1972.

Anderson, Davis, Dove and Griggs, Neurology (1973), 764 studied the effect of PHT on cardiac conduction in patients who suffered from myotonic dystrophy. They found that PHT was beneficial, not only for the myotonia, but also for cardiac conduction defects common in this disease. In five of eight patients treated with oral PHT the P-R interval was shortened by 5 to 35 msec. This was in marked contrast to quinine and procainamide. Quinine produced P-R interval prolongation in four of ten patients, and procainamide produced P-R interval prolongation in nine of ten patients. The authors’ studies indicate diffuse involvement of the His-Purkinje system in myotonic dystrophy. They note that studies by others in normal subjects have shown a depression of His-Purkinje conduction with procainamide and quinine, but not with PHT.

764. Anderson, D. C., Davis, R. J., Dove, J. T., and Griggs, R. C., Cardiac conduction during treatment of myotonia, Neurology, 23: 390, 1973.

Bissett, DeSoyza, Kane and Murphy, The American Journal of Cardiology (1974), 831 directly measured conduction in the His-Purkinje system in fourteen patients and found that PHT improved intraventricular conduction. Utilizing the introduction of premature atrial beats, the relative refractory period of the His-Purkinje system and the functional refractory period of the atrioventricular (A-V) node were measured in the fourteen patients before and after administration of PHT. Before infusion of PHT, His-Purkinje conduction delay occurred with right bundle branch block in nine patients, and with left bundle branch block in five patients. After intravenous PHT (5 mg/kg at a rate of 50 mg/min) the onset or degree of His-Purkinje delay was improved in all patients. In the nine patients, PHT reduced the relative refractory period of the His-Purkinje system to a value of less than that of the functional refractory period of the AV node, so that His-Purkinje conduction delay no longer occurred after PHT. In the five patients with left bundle branch block, PHT also reduced the relative refractory period of the His-Purkinje system or altered the degree of aberrant conduction, or both. The authors note that the present study demonstrates that PHT improves intraventricular conduction in man.

831. Bissett, J. K., deSoyza, N. D. B., Kane, J. J., and Murphy, M. L., Improved intraventricular conduction of premature beats after diphenylhydantoin, Amer. J. Cardiol., 33: 493-497, 1974.

Quiret, Bens, DuBoisset, Lesbre and Bernasconi

, Archives des Maladies du Coeur et des Vaisseaux (1974), 1434 studied the cardiovascular effects of PHT in 105 patients. The authors say that PHT appears to have the following properties. It favors, or in any case does not adversely affect, atrioventricular conduction as well as intraventricular conduction. It checks manifestations of atrial and/or ventricular hyperexcitability secondary to organic cardiopathy or an excess of digitalis and has little or no effect on sinoatrial automatism.

1434. Quiret, J. C., Bens, J. L., Duboisset, M., Lesbre, P. and Bernasconi, P., Diphenylhydantoin injectable in cardiology, Arch. Mal. Coeur., 67: 87-96, 1974.

Dhatt, Akhtar, Reddy, Gomes, Lau, Caracta and Damato, Circulation (1977),1804 studied effects of PHT on macro-re-entry within the His-Purkinje system in ten patients. In seven patients, PHT modified determinants of re-entry and abolished re-entry in three patients. In all patients PHT significantly shortened functional and effective refractory periods of the His-Purkinje system, without affecting the effective refractory period of the ventricular muscle. PHT either abolished or significantly shortened the retrograde gap zones in the His-Purkinje system.

1804. Dhatt, M. S., Akhtar, M., Reddy, C. P., Gomes, J. A. C., Lau, S. H., Caracta, A. R. and Damato, A. N., Modification and abolition of re-entry within the His-Purkinje system in man by diphenylhydantoin, Circulation, 56(5): 720-26, 1977.