INTRACELLULAR CALCIUM TRANSIENTS UNDERLYING INTERVAL FORCE RELATIONSHIP IN WHOLE RAT HEARTS - EFFECTS OF CALCIUM-ANTAGONISTS

Objectives: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolate d muscle studies. We tested whether results from isolated muscles abou t intracellular Ca2(+)([Ca2+](i)) transients underlying the interval-f orce relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+](i) transie nts underlying mechanical restitution and postextrasystolic potentiati on. Methods: [Ca2+](i) transients were studied in isolated perfused ra t hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+](i) (developed pressure and [Ca2+](i) pl otted as a function of extrasystolic intervals), To quantify restituti on curves, we fitted monoexponential functions to plots and analyzed t heir shift and slope. Then, we used Ca2+ antagonists, low extracellula r Ca2+([Ca2+](0)) and PESP to modify restitution curves. [Ca2+](i) tra nsients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. Results: Interval-dependent changes in dev eloped pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+](i) transients in isolated whole rat hearts . Additionally, nifedipine and low [Ca2+](0) led to similar downward s hifts but not to a changed slope of restitution curves for [Ca2+](i). On the other hand, PESP increased the slope of restitution curves for [Ca2+](i), Furthermore, the effect of PESP on developed pressure was b lunted by high concentrations of Ca2+ antagonists. Conclusions: The re sults from isolated muscles about [Ca2+](i) transients underlying the interval-force relationship could be substantiated in whole hearts. Ad ditionally, low [Ca2+](i) (induced by nifedipine or low [Ca2+](0)) dec reased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably ac celerated Ca2+ release kinetics of the sarcoplasmic reticulum.