Bonoron-Adèle S, Grellet J, Bricaud H, Tariosse L, Besse P
Arzneimittelforschung. 1986 Nov;36(11):1572-7.
The present study intended to investigate the effects of 2-[2-methoxy-4-(methylsulfinyl)phenyl]-3H-imidazo[4,5-b]pyridine (sulmazole, AR-L 115 BS) on mechanical performance of rat myocardial fibers under hypoxia, and subsequent reoxygenation. Because of a possible caffeine-like mechanism of action of sulmazole similar experiments were performed with theophylline and the results compared. 1. Under normoxic conditions, sulmazole and theophylline displayed a positive inotropic action with acceleration of relaxation at small concentrations (sulmazole: 6.4 mumol l-1; theophylline 7.35 mumol l-1). Increasing doses led to a negative inotropic effect with slackened relaxation and loss of its load sensitivity (up to 390 mumol l-1 for sulmazole; up to 350 mumol-1 for theophylline). In agreement with other reports, the dose-effect curve was shifted towards low concentrations. 2. During ischemic crisis, therapeutic doses of sulmazole (6 mumol l-1) and theophylline (7 mumol l-1) induced no additional depression of contractility and protected relaxation. During subsequent reoxygenation, better recovery of contractility was observed without any very significant improvement of relaxation. 3. During reoxygenation beyond 120 mumol l-1, increasing doses of sulmazole depressed contractility. An additional depressive effect on mechanical performance was observed during hypoxia only for the highest dose (390 mumol-1).
本研究旨在探究2-[2-甲氧基-4-(甲基亚磺酰基)苯基]-3H-咪唑并[4,5-b]吡啶（舒马唑，AR-L 115 BS）对大鼠心肌纤维在缺氧及随后复氧情况下力学性能的影响。由于舒马唑可能具有类似咖啡因的作用机制，因此用茶碱进行了类似实验并比较结果。1. 在常氧条件下，舒马唑和茶碱在低浓度时（舒马唑：6.4 μmol l-1；茶碱7.35 μmol l-1）呈现正性肌力作用，伴有舒张加速。剂量增加会导致负性肌力作用，舒张松弛且失去负荷敏感性（舒马唑高达390 μmol l-1；茶碱高达350 μmol-1）。与其他报道一致，剂量-效应曲线向低浓度方向移动。2. 在缺血危机期间，治疗剂量的舒马唑（6 μmol l-1）和茶碱（7 μmol l-1）未引起额外的收缩力抑制，并保护了舒张功能。在随后的复氧过程中，观察到收缩力有更好的恢复，但舒张功能没有非常显著的改善。3. 在复氧超过120 μmol l-1时，舒马唑剂量增加会抑制收缩力。仅在最高剂量（390 μmol-1）时，在缺氧期间观察到对力学性能有额外的抑制作用。
