Effects of Ca antagonists on the sinoatrial and atrioventricular nodes

19 EFFECTS OF Ca ANTAGONISTS ON THE SINOATRIAL AND ATRI0VENTRICULAR NODES. C. Kawai, T. Konishi, E. M a t s u y a ~ , H. 0kazaki. 3rd Division, Dept. of Int. Med., Faculty of Med., Kyoto University, Kyoto, Japan Effects of three Ca antagonists, verapamil (V), diltiazem (D), and nifedipine (N) were examined experimentally and clinically on the sinoatrial node (SAN) and the atrioventricular node (AVN) where the upstrokes of transmembrane action potential are claimed to depend on slow inward currents. IMethod]~ Transmembrane resting and action potentials (RP, AP) were recorded with the conventional microelectrode technique from the cells in l) SAN and crista terminalis (CT) and 2) AVN and His bundle (HB) in excised and superfused rabbit right atria. The modes of electrical stimulation via p l a t i n u m w i r e electrodes were l) 30 second overdrive from CT and 2) one premature stimulus in every 8th basic stimulus from CT or interatrial septum. Sinus recovery time (SRT) and effective and functional refractory periods (ERP, FRP) of AVN were measured before and 15 minutes after the application of each Ca antagonist into the Tyrode bath in a final concentration of 10-7 to l0 -6 g/ml. During diagnostic cardiac catheterization, ERP and FRP of A V N w e r e measured by extra-stimulus method and SRT by 30 second overdrive. These measurements were repeated after intravenous injection of V(10mg), D(10-20mg) or N(lmg). ~Results and conclusions]: l) V, D, and N caused equally dose-dependent bradycardia to sinus arrest and prolongation of SRT in excised rabbit SAN preparations. As field stimulation evoked only abortive responses in arrested SAN cell in which RP was well maintained, the effect appeared to be not only on phase 4 but on phase 0 of AP. 2) Effect of Ca antagonists on human SAN was supposed to be rather complicated by changing sympathetic activity as the result of vasodilating action which is most potent in N. 3) The three agents lengthened ERP and FRP almost equally in excised rabbit AVN preparations. These results also hold true for clinical investigations except for N. V given intravenously was highly effective in treating AV junctional reentrant tachycardia; the reentrant circuit was always blocked Within AVN (A-H block). Intravenous injection of lmg of N shortened paradoxically SRT, EEP and FRP, probably due to increase in sympathetic tone secondary to its hypotensive effect which prohibited clinically from using the same amount of N as V or D.