Riou B, Lecarpentier Y, Barriot P, Viars P
Institut National de la Santé et de la Recherche Médicale, Unité 275, LOA-ENSTA-Ecole Polytechnique, Palaiseau, France.
Intensive Care Med. 1989;15(6):390-5. doi: 10.1007/BF00261499.
Diazepam has been reported to decrease the cardiac toxicity of chloroquine but the precise mechanism involved remains unknown. Left ventricular papillary muscles from adult Wistar rats were exposed to 10(-4) M chloroquine and assigned to three groups: group I (n = 10) exposed to chloroquine alone; group II (n = 8) exposed to chloroquine and 10(-5) M diazepam; group III (n = 8) exposed to chloroquine and 10(-4) M diazepam. The main mechanical parameters measured were: maximum unloaded shortening velocity (Vmax), maximum lengthening velocity (maxVr), active force normalized per cross-sectional area (AF/s), contraction-relaxation coupling under low load (R1), load sensitivity of relaxation (Isot.A/Isom.A), and peak power output (Emax) determined from Hill's equation of the force-velocity curve. Data are expressed as mean percent of control values +/- SD, for groups I, II, III respectively. No differences between groups I, II, and III were noted for Vmax (87 +/- 13, 82 +/- 9, 86 +/- 7), maxVr (47 +/- 6, 48 +/- 11, 52 +/- 11), AF/s (87 +/- 16, 91 +/- 10, 83 +/- 11), Isot. A/Isom. A (113 +/- 9, 108 +/- 3, 109 +/- 7), or Emax (75 +/- 10, 81 +/- 12, 72 +/- 16). Chloroquine was shown to be a negative inotropic agent since it decreased Vmax, AF/s and Emax, but diazepam did not restore the intrinsic mechanical performance of rat cardiac papillary muscle exposed to chloroquine, therefore 1) the protective cardiovascular effects of diazepam in chloroquine poisoning are not related to an improvement in intrinsic cardiac mechanical properties; 2) inotropic agents are therefore necessary in combination with diazepam for the treatment of severe chloroquine poisoning.
据报道，地西泮可降低氯喹的心脏毒性，但具体机制尚不清楚。将成年Wistar大鼠的左心室乳头肌暴露于10(-4)M氯喹，并分为三组：第一组（n = 10）仅暴露于氯喹；第二组（n = 8）暴露于氯喹和10(-5)M地西泮；第三组（n = 8）暴露于氯喹和10(-4)M地西泮。测量的主要力学参数有：最大无负荷缩短速度（Vmax）、最大延长速度（maxVr）、每横截面积归一化的主动力（AF/s）、低负荷下的收缩-舒张耦联（R1）、舒张的负荷敏感性（Isot.A/Isom.A）以及根据力-速度曲线的希尔方程确定的峰值功率输出（Emax）。数据分别表示为第一组、第二组、第三组相对于对照值的平均百分比±标准差。第一组、第二组和第三组在Vmax（87±13、82±9、86±7）、maxVr（47±6、48±11、52±11）、AF/s（87±16、91±10、83±11）、Isot.A/Isom.A（113±9、108±3、109±7）或Emax（75±10、81±12、72±16）方面未观察到差异。氯喹被证明是一种负性肌力药物，因为它降低了Vmax、AF/s和Emax，但地西泮并未恢复暴露于氯喹的大鼠心脏乳头肌的固有力学性能，因此1）地西泮在氯喹中毒中的心血管保护作用与心脏固有力学性能的改善无关；2）因此，在治疗严重氯喹中毒时，正性肌力药物与地西泮联合使用是必要的。
