Lavanchy N, Martin J, Rossi A
J Mol Cell Cardiol. 1986 Sep;18(9):931-41. doi: 10.1016/s0022-2828(86)80007-4.
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.
通过对逆行灌注的大鼠心脏进行31P核磁共振波谱分析（101.3兆赫），研究了10(-6)M地尔硫卓（DZ）对缺血诱导的代谢损伤可能产生的直接减轻作用。这些大鼠心脏先经历24分钟的常温（37摄氏度）全心低流量缺血（缺血前自发冠状动脉血流量的1%），随后再灌注30分钟。10(-6)M DZ的存在既不改变常氧条件下的心率和左心室内压，也不改变缺血期间ATP和CP的消耗程度，而缺血期间心肌内Pi的积累显著减少（约30%）。在DZ存在的情况下，缺血诱导的细胞内酸化最初较小，但缺血结束时达到的pH值略低于对照组（尽管差异不显著）：5.85±0.07对6.00±0.07（平均值±标准误）。再灌注时，DZ处理的心脏比对照心脏表现出更大的氧化磷酸化能力。实际上，核磁共振波谱显示，DZ处理的心脏中肌酸的再磷酸化更迅速、更显著且更持久，同时Pi含量同步更快且更急剧下降。此外，尽管核磁共振波谱未显示DZ处理的心脏与对照心脏在再灌注时ATP变化有任何显著差异，但生化测量表明再灌注结束时ATP含量略高，更特别的是，腺苷酸能荷的恢复更好：0.81±0.03对0.72±0.03，平均值±标准误（缺血前值0.90 - 0.91）。DZ处理的心脏在再灌注结束时细胞内pH与其缺血前值无显著差异（7.08），而对照组仍低于初始值（7.00）。从这些结果可以推断，在相对低浓度（10(-6)M）时，DZ对缺血心脏的能量代谢产生直接有益作用，在缺血期间不保留高能磷酸化合物，最重要的是，不降低伴随的细胞内酸化程度。
