Energy preserving effect of l-cis diltiazem in isolated ischemic and reperfused guinea pig hearts: a 31P-NMR study.
We determined the effect of 1-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 microM l-cis diltiazem than by 3 microM diltiazem or 500 nM nifedipine. However, 10 microM 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 microM l-cis diltiazem, showed no cardioprotective effect. Ten micromolar l-cis diltiazem and 3 microM 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.
Sakamoto
K
K
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Ishikawa
M
M
Koga
K
K
Urushidani
T
T
Nagao
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009200:Myocardial Contraction; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009543:Nifedipine / Q000494:pharmacology; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes
D002121:Calcium Channel Blockers; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D004110:Diltiazem; D009543:Nifedipine