Vander Elst L, Chatelain P, Manning A S, Laruel R, Van Haverbeke Y, Muller R N
University of Mons Hainaut, NMR Laboratory, Faculty of Medicine, Mons, Belgium.
Eur J Pharmacol. 1994 Jan 14;251(2-3):163-72. doi: 10.1016/0014-2999(94)90397-2.
The biochemical and mechanical effects of a new calcium ion channel antagonist, fantofarone ((2-isopropyl-1-((4-(3-(N-methyl-N-(3,4-dimethoxy-beta-phenethyl)-amino) propyloxy)benzenesulfonyl))-indolizine), on isovolumic perfused rat heart have been assessed by using 31P nuclear magnetic resonance (NMR) spectroscopy together with simultaneous monitoring of myocardial mechanical function. Cytosolic pH and phosphocreatine, adenosine triphosphate and inorganic phosphate contents were monitored by using 31P NMR. Heart rate, coronary flow and left ventricular developed pressure were measured routinely to assess mechanical function. Perfusion with 10 nM, 100 nM or 1 microM fantofarone for a period of 48 min did not cause any measurable metabolic changes. However, coronary vasodilatation and a partial positive inotropic effect were noted. A 15-min pretreatment with 100 nM did not protect against the deleterious effects of an 18-min period of normothermic, zero-flow ischemia. In contrast, a 20-min pretreatment period with 1 microM fantofarone significantly improved the recovery of mechanical performance, metabolic activity and pH after the same 18 min of ischemia. While only a slight protection of the ATP pool was noted during the ischemic period, major beneficial effects were observed during the reperfusion period, such that reflow was characterized by high recoveries of left ventricular pressure and rate pressure product (70-80%), low end diastolic pressure (< 10 mm Hg), significant recovery of ATP content (to 55%), a complete repletion of the phosphocreatine pool and a fast return of cytosolic pH to normal value.
一种新型钙离子通道拮抗剂凡托法隆（(2-异丙基-1-((4-(3-(N-甲基-N-(3,4-二甲氧基-β-苯乙胺基)丙氧基)苯磺酰基))-中氮茚）对离体大鼠心脏等容灌注的生化和机械效应，已通过使用31P核磁共振（NMR）光谱并同时监测心肌机械功能进行了评估。利用31P NMR监测细胞内pH值以及磷酸肌酸、三磷酸腺苷和无机磷酸盐的含量。常规测量心率、冠状动脉血流量和左心室舒张末期压力以评估机械功能。用10 nM、100 nM或1 μM凡托法隆灌注48分钟未引起任何可测量的代谢变化。然而，观察到冠状动脉血管舒张和部分正性肌力作用。用100 nM进行15分钟预处理并不能预防18分钟常温零流量缺血的有害影响。相比之下，用1 μM凡托法隆进行20分钟预处理可显著改善相同18分钟缺血后机械性能、代谢活性和pH值的恢复。虽然在缺血期仅观察到对三磷酸腺苷池的轻微保护作用，但在再灌注期观察到主要的有益作用，即再灌注的特征为左心室压力和心率压力乘积的高恢复率（70 - 80%）、低舒张末期压力（< 10 mmHg）、三磷酸腺苷含量的显著恢复（至55%）、磷酸肌酸池的完全补充以及细胞内pH值快速恢复至正常值。
