Metabolism of the perfused rabbit heart. V. Verapamil-induced release of creatine kinase.

The effects of verapamil (VER), at concentrations of 0 X 10(-9) X 10(-8) X 10(-7), and 5 X 10(-7) M (or 0, 0.5, 5, 50, and 250 ng/mL) were studied in the isolated rabbit heart during 70 min of aerobic perfusion with a standard Krebs-bicarbonate medium at 37 degrees C. The studied variables were left ventricular performance (RPP, heart rate times left ventricular (LV) systolic pressure), coronary sinus flow (CSF), oxygen uptake (MVO2), rate of creatine kinase (CK) release, and energy stores (glycogen, creatine phosphate (CP), ATP, and total adenine nucleotides (TAN) ). The results show that (i) VER depressed RPP in a dose-related manner: (ii) MVO2 declined as VER concentration increased except in the 5 x 10(-7) M group which showed a paradoxical increase in O2 uptake; (iii) CSF was only slightly decreased by VER with the exception of the 5 x 10(-7) M group, which showed an increase in flow; (iv) VER was associated with increments in the rates of CK release in a dose-related fashion (2, 4, 15, and 29 times the rate observed in the untreated group), and (v) VER was associated with slight decrease in glycogen levels, but no changes in CP or adenine nucleotides. It is concluded that, in our preparation, VER caused marked increases in the rate of CK loss in the absence of depletion of total energy stores. The data suggest that the drug affects the permeability characteristics of the sarcolemma, perhaps via localized depletion of calcium stores.