CALCIUM-ANTAGONIST EFFECTS OF NORBORMIDE ON ISOLATED-PERFUSED HEART AND CARDIAC MYOCYTES OF GUINEA-PIG - A COMPARISON WITH VERAPAMIL

1 Cardiac effects of norbormide and verapamil were compared in single ventricular myocytes, right atria, and Langendorff perfused hearts iso lated from guinea-pigs. 2 In ventricular myocytes, norbormide 50 mu M inhibited the peak calcium current (I-ca) by 49.6+/-3.9% without alter ing the shape of the current-voltage relationship; verapamil 1 mu M in hibited I-ca by 83.2+/-3.3%. Neither norbormide nor verapamil affected I-ca at the first beat after a 3 min quiescence period; during repeat ed depolarizations, both drugs cumulatively blocked Ic, (use-dependenc e), with time constants of 23.0+/-7.0 s for norbormide and 91.3+/-8.4 s for verapamil. 3 In constant-flow perfused hearts electrically drive n at 2.5 Hz or 3.3 Hz, both norbormide and verapamil concentration-dep endently decreased ventricular contractility (dP/dt(max)), atrio-ventr icular (AV) conduction velocity and coronary pressure. Intraventricula r conduction velocity was slightly decreased by norbormide but not by verapamil. At an equivalent change in AV conduction, norbormide depres sed heart contractility less than verapamil. The effects of norbormide on AV conduction, intraventricular conduction, and contractility were frequency-dependent. Furthermore, the curves correlating the mechanic al and electrical effects of norbormide at the two frequencies used we re apparently coincident, while those of verapamil were clearly separa ted. 4 In spontaneously beating right atria, norbormide and verapamil decreased the frequency of sinus node (SA) in a concentration-dependen t way. At an equivalent effect on the AV conduction, norbormide exerte d a greater effect on sinus frequency than verapamil. 5 These results indicate that in guinea-pig heart norbormide has the pharmacological p rofile of a Ca-antagonist with strong electrophysiological properties. In comparison with verapamil, norbormide is more selective on SA and AV node tissues and exerts a weaker negative inotropic effect on ventr icles. In principle, this pattern of effects may be an advantage in tr eating supraventricular tachyarrhythmias in patients with heart failur e. The effect of norbormide on intraventricular conduction may represe nt an additional antiarrhythmic mechanism.