Abstract
Isolated canine Purkinje fibers were mounted in a tissue chamber perfused with Tyrode's solution and studied under control conditions and during perfusion with phentolamine, 1 x l0-8 to 2 x 10-4 M. Standard microelectrode techniques were utilized to record changes in action potential characteristics, effective refractory period, membrane responsiveness and conduction time of electrically driven preparations and automaticity of those beating spontaneously. Consistent changes were not seen in phentolamine, < 10-5 M. In phentolamine, 10-5 M, resting membrane potential, action potential amplitude and maximal rate of rise of phase O depolarization decreased. These changes increased progressively through phentolamine, 10-4 M, and thereafter remained unchanged. Action potential duration was maximal in 5 x 10-5 M, thereafter maintaining a plateau. Effective refractory period increased concomitantly with action potential duration through concentrations of 10-5 M. With greater concentrations, effective refractory period was prolonged to a lesser extent. This effect is unlike that described for the antiarrhythmic agents quinidine and procaineamide. Phentolamine, 10-5 M, depressed membrane responsiveness curves and led to a simultaneous increase in conduction time measured between two intracellular microelectrodes. These changes increased progressively through phentolamine, 10-4 M, thereafter remaining unchanged. Automaticity of spontaneously beating preparations decreased in phentolamine, 10-5 M. All changes were reversible within 100 minutes of Tyrode's solution perfusion. Unlike other antiarrhythmic drugs, phentolamine does not prolong effective refractory period with relation to action potential duration. However, its effects on automaticity and conduction time suggest these may be the means by which it exerts its effects upon ventricular arrhythmias.
Footnotes
- Received June 7, 1971.
- Accepted September 7, 1971.
- © 1971 by The Willams & Wilkins Co.