The effects of calcium antagonists on extracellular potassium accumulation during global ischaemia in isolated perfused rat hearts

The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium [K+]out and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experiments. Diltiazem (2 x 10(-6), 3 x 10(-6), and 10(-5) M), verapamil (3 x 10(-8), 10(-7), and 3 x 10(-7) M), and nifedipine (3 x 10(-8), 10(-7), and 1.5 x 10(-7) M) were able to slow, in a concentration-dependent manner, the initial rate of rise of [K+]out without affecting the final plateau value of [K+]out reached at t = 5 to t = 10 minutes. Notably, at the lowest concentrations, which slightly influenced LVP diltiazem, verapamil, and to a lesser degree nifedipine, were still able to slow the rise in [K+]out. In addition, after preperfusion with low-calcium media [( Ca2+] from 1.8 to 1.3 or 0.9 mM), inducing similar negative inotropic effects as those of the calcium antagonists, the rise in [K+]out was not significantly influenced. Our data indicate that the ability to slow the rise in [K+]out is a specific characteristic of calcium antagonists that is independent of their negative inotropic effects