Mechanism of additive effects of digoxin and quinidine on contractility in isolated cardiac muscle

To evaluate the mechanism of the effect of the interaction of digoxin and quinidine on myocardial contractility, ferret right ventricular papillary muscles were isolated and the effects of digoxin, 4 × 10^{?7 M}, quinidine, 1 × 10⁵M and atropine, 1.5 × 10^?6M, on peak developed force, peak rate of development of force (dF/dt) and time to peak tension were determined. The addition of quinidine to muscles treated with digoxin increased developed force 18 percent (p = 0.006) and dF/dt 37 percent (p = 0.001) without significantly changing time to peak tension. This effect was abolished by pretreatment with atropine. Quinidine alone increased developed force 35 percent (p < 0.001) and dF/dt 70 percent (p < 0.001) and decreased time to peak tension 22 percent (p < 0.001) from pretreatment control values. Atropine alone increased developed force 17 percent (p = 0.02) and dF/dt 32 percent (p = 0.001) and decreased time to peak tension 13 percent (p = 0.003) from pretreatment control values. The addition of quinidine to muscles treated with atropine or of atropine to muscles treated with quinidine did not significantly change developed force, dF/dt or time to peak tension from values with either drug alone.It is concluded that digoxin and quinidine in these doses have additive effects on myocardial contractility, and that this interaction is at least partially mediated through antagonism of cholinergic influences by quinidine.