Author + information
- Received July 20, 1982
- Revision received March 9, 1983
- Accepted March 11, 1983
- Published online August 1, 1983.
- Masao Nishimura, MD and
- Yoshio Watanabe, MD, FACC*
- ↵*Address for reprints: Yoshio Watanabe, MD, Cardiovascular Institute, Fujita Gakuen University School of Medicine, Toyoake, Aichi 470–11, Japan.
Electrophysiologic effects of bretylium tosylate on transmembrane action potentials of canine Purkinje fibers were studied by microelectrode methods. Perfusion of this agent (20 mg/liter) prolonged the action potential duration and the effective refractory period, but did not alter the maximal diastolic potential, upstroke phase of the action potential and membrane responsiveness curve under normal oxygenation. With a hypoxic superfusion, the action potential amplitude, maximal diastolic potential, maximal rate of depolarization and action potential duration were all decreased. Subsequent addition of bretylium antagonized all these effects of hypoxia and restored the action potential variables to control values. However, similar effects of hypoxia observed in Purkinje fibers pretreated with reserpine were not reversed by bretylium except for a prolongation of repolarization.
These results suggest that antiarrhythmic effects of bretylium in hypoxic or depressed myocardium are probably due to: 1) increased maximal rate of depolarization (and conduction velocity) caused by membrane hyperpolarization, and 2) prolongation of the effective refractory period. The first electrophysiologic action appears to depend on catecholamine release by bretylium, as hyperpolarization was not observed in reserpine-pretreated Purkinje fibers. The second effect may represent a direct membrane action.
This study was supported by Grant-in-Aid for Encouragement of Young Scientists from the Ministry of Education, Science and Culture of Japan
- Received July 20, 1982.
- Revision received March 9, 1983.
- Accepted March 11, 1983.
- American College of Cardiology Foundation