Intracellular calcium transients underlying interval-force relationship in whole rat hearts : effects of calcium antagonists

• Published in: Cardiovascular research 1995-08, Vol.30 (2), p.212-221
• Main Authors: ZAUGG, C. E, KOJIMA, S, WU, S. T, WIKMAN-COFFELT, J, PARMLEY, W. W, BUSER, P. T
• Format: Article
• Language: English
• Subjects: Animals; Antianginal agents. Coronary vasodilator agents; Biological and medical sciences; Biological Transport, Active; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cardiac Pacing, Artificial; Cardiovascular system; Fluorometry; Indoles; Intracellular Fluid - metabolism; Medical sciences; Myocardial Contraction; Myocardium - metabolism; Nifedipine - pharmacology; Perfusion; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Sarcoplasmic Reticulum - metabolism
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/0008-6363(95)00020-8

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 isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. [Ca2+]i transients were studied in isolated perfused rat 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 plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. Interval-dependent changes in developed 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+]o led to similar downward shifts 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 blunted by high concentrations of Ca2+ antagonists. The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulum.