Mechanisms of the Beneficial Effects of Some Ca2+ Antagonists on the Ca2+-Paradox in Myocardium

  • N. S. Dhalla
  • P. K. Singal
  • S. Takeo
  • D. B. McNamara
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 39)


Electrophysiological experiments have provided evidence that Ca2+ antagonists such as verapamil and diltiazem alter cardiac function by inhibiting the entry of Ca2+ through slow calcium channels (1–3). These agents therefore can be seen to protect myocardium under pathophysiological conditions which are associated with a massive amount of Ca2+ entry and the occurrence of intracellular Ca2+ overload. Reperfusion of an isolated rat heart with a medium containing Ca2+ after a brief period of perfusion with a Ca2+ -free medium has been shown to produce contractile abnormalities, myocardial cell damage, depletion of high energy phosphate stores, alterations in cation contents, enzyme leakage and changes in subcellular Ca2+ -transport (5–12). These Ca2+ -paradoxic effects have been attributed to the occurrence of intracellular Ca2+ -overload (8); however, the mechanisms of these changes in the myocardium are far from clear. Some investigators have shown the protective effects of both verapamil and diltiazem against the Ca2+ -paradox related myocardial injury and have interpreted their results to mean that the massive Ca2+ -influx during Ca2+ -paradox is occurring through the slow calcium channels (13–15). On the other and, concentrations of verapamil, which are known to block Ca2+ -currents, were reported to be ineffective in preventing the Ca2+ -paradoxic changes (16,17). Accordingly, it has been suggested that some other mechanism of Ca2+ influx or efflux such as Na –Ca2+ exchange may also be involved in eliciting Ca2+ -paradoxic effects on the myocardium (18,19). This study was therefore undertaken to examine the effects of both low and high concentrations of verapamil and diltiazem on some Ca2+ -paradox changes in the myocardium. Furthermore, the actions of these agents Na+ -Ca2+ exchange mevhanism in the sarcolemmal preparations were studied.


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Copyright information

© Martinus Nijhoff Publishing, Boston 1984

Authors and Affiliations

  • N. S. Dhalla
    • 1
  • P. K. Singal
    • 1
  • S. Takeo
    • 1
    • 2
  • D. B. McNamara
    • 1
  1. 1.Experimental Cardiology Section, Department of Physiology, Faculty of MedicineUniversity of ManitobaWinnipegCanada
  2. 2.Department of Pharmacology, School of MedicineUniversity of RyukyusNahaJapan

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