Influence of low extracellular Ca2+ ions on the cardiac function changes induced by verapamil in the perfused rabbit heart
We tested the hypothesis that the myocardial effects of verapamil (VER) could be enhanced by decreasing the extracellular Ca2+ concentration ([Ca2+]o) in the isolated rabbit heart at 37 °C. After perfusion with standard Krebs–bicarbonate solution containing 1.27 mM Ca2+, for a 30-min period of stabilization and 15 min of control, groups of hearts were perfused for an additional 60 min with solutions containing one of the following: 1.27 mM Ca2+ (control group), 0.23 mM Ca2+ (low [Ca2+]o group), 1.27 mM Ca2+ plus 10− M VER (VER group), or 0.23 mM Ca2+ plus 10−7 M VER (combination, CBN group). These concentrations of [Ca2+]o and VER produce submaximal responses in our preparation. We found that the heart rate – LV pressure product (RPP) in the CBN group fell rapidly to 0 in the first 2–3 min of perfusion, this response being significantly lower than in the other two groups for the first 15 min. Electromechanical dissociation (EMD) appeared in one of six hearts at 60 min and in four of six hearts at 30 min in the low [Ca2+]o and VER groups, respectively, whereas it occurred in the CBN group in all hearts at 3 min. Depolarization rate (DR) fell by 10% in the low [Ca2+]o and VER groups versus a reduction of 45% in the CBN group (P < 0.05) during the last 45 min of perfusion. The PR interval increased by 300% in the CBN group, a much greater and significant change (P < 0.05) than in the hearts exposed to VER or low [Ca2+]o. The QT interval, however, increased by 50% in the low [Ca2+]o group (P < 0.05) and decreased by 20–30% in the VER and CBN groups (P < 0.05). On the other hand there were no differences in the changes in coronary sinus flow, O2 uptake, enzyme release, or energy stores among the groups. We conclude that low [Ca2+]o enhanced the effects of VER in relation only to RPP, DR, PR interval, and possibly EMD, but had no influence on metabolism.