THE CARDIAC ELECTROPHYSIOLOGICAL EFFECTS OF SPARTEINE AND ITS ANALOG BRB-I-28 IN THE RAT

This study compares the cardiovascular and antiarrhythmic effects of s parteine and a 3,7-diheterobicyclo[3.3.1]nonane analogue of sparteine, BRB-1-28, in pentobarbitone-anaesthetized rats subjected to left-vent ricle electrical stimulation and occlusion of the left anterior descen ding coronary artery. Sparteine and BRB-1-28 produced a dose-dependent reduction in heart rate and blood pressure over the dose range 1-64 m u mol/kg/min. As well, the P-R and Q-aT intervals of the electrocardio gram (EGG) were prolonged. The thresholds for induction of premature b eats and ventricular fibrillation were dose-dependently increased and both drugs increased refractoriness. While sparteine and BRB-1-28 (at 16 and 64 mu mol/kg/min, respectively) did not change the incidence of premature beats or ventricular tachycardia with coronary occlusion, b oth drugs equally reduced the incidence of ventricular fibrillation. W e characterized the actions of sparteine and BRB-1-28 on cardiac Na+, transient outward and sustained outward plateau K+ currents of rat myo cytes using the whole-cell patch-clamp. Sparteine and BRB-1-28 produce d a concentration-dependent reduction in Na+ current with EC(50) value s of 110 and 230 mu M, respectively. Both drugs produced hyperpolarizi ng shifts of 8 and 11 mV, respectively, for Na+ channel inactivation w hile neither produced a change in channel activation. Both drugs produ ced a concentration-dependent block of the sustained plateau K+ curren t and increased the rate of decay of the transient outward K+ current. Thus, sparteine and BRB-1-28 possess Na+ and K+ channel blocking prop erties which may account for their antiarrhythmic actions against elec trical and ischaemic arrhythmias.