Electrophysiological actions of BRB-I-28 in canine myocardial tissues

To obtain a better understanding of the possible electrophysiological bases of the antiarrhythmic actions of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate (BRB-I-28), microelectrode recordings of myocardial electrical activity were obtained in canine Purkinje and ventricular tissue, and in isolated canine ventricular myocytes. BRB-I-28 (1.0 and 3.2 mg/l) reduced Vmax, action potential amplitude, overshoot potential and conduction velocity in Purkinje tissues without altering action potential duration or spontaneous automaticity. Vmax and conduction velocity were reduced only at paced cycle lengths of 500 msec or less. BRB-I-28 (3.2 and 10 mg/l) also reduced Vmax, action potential amplitude and overshoot potential in subendocardial and epicardial ventricular muscle, with Vmax reduced only at cycle lengths of 500 msec or less. Recovery half-times for Vmax estimated in canine subendocardium were 330 +/- 28 and 336 +/- 25 msec at BRB-I-28 concentrations of 3.2 and 10 mg/l, respectively. In epicardium, conduction velocity longitudinal to fiber orientation was depressed more than conduction velocity transverse to fiber orientation, despite similar changes in Vmax. In both epicardial and subendocardial ventricular muscle, a reduction in Vmax is observed in the absence of alterations in action potential duration. Experiments using myocytes isolated from canine epicardial tissue demonstrated similar rate-dependent changes in Vmax as ventricular epicardium. The data demonstrate a rate-dependent depression of Vmax by BRB-I-28 in canine ventricular tissues. The depression of conduction occurs only at rapid paced rates and occurs in the absence of changes in Purkinje cell automaticity or action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)