Energy Preserving Effect of l-cis Diltiazem in Isolated Ischemic and Reperfused Guinea Pig Hearts: A ^<31>P-NMR Study

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We determined the effect of l−cis diltiazem, the enantiomer of diltiazem(d−cis isoform), on the energy metabolism of isolated guinea pig hearts during ischemia−reperfusion.We used 31P−NMR to measure the high−energy phosphate content and intracellular pH(pHi)during global ischemia for 30 min followed by reperfusion for 30 min.Before ischemia, the left ventricular developed pressure(LVDP)was reduced less by 10 μM l−cis diltiazem than by 3 μM diltiazem or 500 nM nifedipine.However, 10 μM l−cis diltiazem preserved the intracellular ATP content during ischemia and reperfusion, reduced the end−diastolic pressure increase during ischemia and reperfusion, and restored LVDP after reperfusion.Nifedipine at 50 nM, which reduced the LVDP more than 10 μM l−cis diltiazem, showed no cardioprotective effect.Ten micromolar l−cis diltiazem and 3 μM diltiazem, but neither 50 nor 500 nM nifedipine, reduced the pHi decrease that occurred 25 or 30 min after the onset of ischemia.Therefore, l−cis diltiazem has a cardioprotective effect on ischemic and reperfused myocardium and is less cardiodepressive than diltiazem and nifedipine.The effect of l−cis diltiazem during ischemia and reperfusion involves energy preservation, which is probably independent of its Ca2+−channel blocking action.
社団法人日本薬理学会の論文
2000-07-01