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  • Title: Prevention of calcium paradox-related myocardial cell injury with diltiazem, a calcium channel blocking agent.
    Author: Ashraf M, Onda M, Benedict JB, Millard RW.
    Journal: Am J Cardiol; 1982 May; 49(7):1675-81. PubMed ID: 6282103.
    Abstract:
    The effect of diltiazem on creatine kinase release and tissue adenosine triphosphate content was investigated during calcium paradox in the isolated perfused rat heart. Creatine kinase loss was minimal during the calcium-free phase, but there was a 100-fold increase in creatine kinase release after reperfusion with normal calcium-containing medium. Diltiazem reduced creatine kinase loss by 35 percent when added to calcium-free medium and by approximately 80 percent when added to both calcium-free and reperfusion media. Adenosine triphosphate content was significantly increased from 2.98 mumol in untreated calcium paradox hearts to 5 mumol/g dry weight in diltiazem-treated hearts. With hypothermia the calcium paradox injury was completely inhibited if the temperature of calcium-free perfusion was maintained at 15 degrees C. Diltiazem appears to exert its protective effect through its ability to prevent the cellular separation and alterations in the gap junctions during calcium deprivation of cells and to limit calcium entry into the cells after reperfusion with calcium-containing medium.
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