Effects of diltiazem on the energy metabolism of the isolated rat heart submitted to ischaemia: a 31P NMR study.

The possible direct attenuating modification by diltiazem (DZ) 10(-6) M of ischaemia-induced metabolic damage was studied by 31P NMR spectroscopy (at 101.3 MHz) on retrogradely perfused rat hearts submitted to a 24 min, normothermic (37 degrees C), global low-flow ischaemia (1% of the pre-ischaemic spontaneous coronary flow), followed by a 30 min reperfusion. The presence of DZ 10(-6) M altered neither the heart rate and the left intraventricular pressure under normoxic conditions, nor the extent of ATP and CP depletion during ischaemia, whilst the intramyocardial Pi accumulation during ischaemia was significantly reduced (by about 30%). The intracellular acidification induced by ischaemia was initially less in the presence of DZ, but the pH values reached by the end of ischaemia were somewhat lower than in control (albeit not significantly so): 5.85 +/- 0.07 v. 6.00 +/- 0.07 (Means +/- S.E.M.). On reperfusion, DZ-treated hearts exhibited a greater oxidative phosphorylation capacity than did control hearts. Indeed, NMR spectroscopy revealed a prompter, greater and durable rephosphorylation of creatine together with a simultaneous more rapid and furthermore sharp drop in Pi content in DZ-treated hearts. Moreover, although NMR spectroscopy did not reveal any significant difference in ATP alteration on reperfusion in DZ-treated hearts as compared with controls, biochemical measurements indicated slightly higher ATP content at the end of reperfusion and, more particularly, a better recovery of the adenylate charge: 0.81 +/- 0.03 v. 0.72 +/- 0.03, means +/- S.E.M. (Pre-ischaemic value 0.90-0.91). The intracellular pH differed insignificantly from its pre-ischaemic value at the end of reperfusion in DZ-treated hearts (7.08), while remaining below initial values in controls (7.00). From these results, it is inferred that, at relatively low concentration (10(-6) M), DZ exerts a direct beneficial effect on the energy metabolism of the ischaemic heart without preserving high-energy phosphate compounds during ischaemia and, most importantly, without reducing the extent of the concomitant intracellular acidification.