Mechanism of negative chronotropic and inotropic effects of some antifibrillatory agents

¹ Department of Pharmacology, University of Southern California School of Medicine, Los Angeles, California

Three compounds, 1,10-phenanthroline, tripyridine, and quinidine sulfate, which have potent antifibrillatory actions on isolated rabbit atria, were found to have negative chronotropic and inotropic effects on spontaneously beating rabbit atria. During the first 15–20 min, a progressive decrease in rate was observed with 1,10-phenanthroline and quinidine. A second period of rate decline was noted during which some of the atrial electrical complexes appeared to drop out. This second phenomenon was also noted with tripyridine. High amplification recording showed a splitting of the electrical complex with subsequent sudden losses of portions of the complex. Both tripyridine and quinidine produced apparent atrial standstill. During the standstill, amplification of the electrical recording showed regular electrical activity with the absence of contractions. It is concluded that quinidine and 1,10-phenanthroline affect the S-A node initially to produce atrial slowing; whereas, all three compounds produce a later atrial slowing by junctional blockade, presumably at anatomic junctions such as the region between the S-A node and the atrium, or at the intercalated discs within the atrium proper. The negative inotropic effects of all three compounds are in part explained by this junctional blockade.

Key Words: negative inotropic effects of quinidine • actions of 1,10-phenanthroline, tripyridine, and quinidine

Submitted on August 7, 1963