A neurally mediated inotropic effect of veratridine and cevadine on isolated guinea-pig papillary muscle.

The positive inotropic effect of veratridine and cevadine was investigated in the isolated, isometrically contracting guinea-pig papillary muscle. The increase of the force of the rested-state contraction, elicited after incubation of the resting muscle with veratridine or cevadine, served as a measure of the neurally mediated, sympathomimetic effect of these alkaloids. Concentrations exceeding 5 mumol/l veratridine or 15 mumol/l cevadine produced concentration-dependent increases of the force of the rested-state contraction. These concentrations are larger than those causing the maximum positive inotropic effect on muscles contracting continually at a rate of 1 Hz. The positive inotropic effect of 30 mumol/l veratridine as manifested by the rested-state contraction was absent in the presence of 100 nmol/l tetrodotoxin and in muscles from reserpine-pretreated animals. It was significantly inhibited by 50 nmol/l (-)-propranolol, but not by the same concentration of (+)-propranolol. The effect of 30 or 60 mumol/l cevadine was likewise absent in catecholamine-depleted preparations. It is concluded that the indirect inotropic effect of veratridine or cevadine, which is attributed to their noradrenaline-releasing effect on intracardiac nerves, requires higher concentrations than the direct positive inotropic effect, which is a consequence of the increased transsarcolemmal influx of Na ions into the myocardial cell.