Joseph T, Coirault C, Ducros L, Lecarpentier Y
INSERM U275, LOA-ENSTA-Ecole Polytechnique, Palaiseau, France.
J Pharmacol Exp Ther. 1996 Nov;279(2):464-71.
The mechanical and energetic effects of the adenosine triphosphate-sensitive potassium channel opener cromakalim at 50 microM and 100 microM were determined on guinea pig left ventricular papillary muscles and compared with those of low calcium concentration (n = 9 in each group). Both concentrations of cromakalim induced a negative inotropic effect (decrease in maximum shortening velocity at preload only and maximum extent of muscle shortening at preload only, P < .01 and P < .001 at 50 and 100 microM, respectively; maximum isometric active force normalized per cross-sectional area during the isometric twitch, P < .001; positive peak of the isometric force derivative normalized per cross-sectional area, P < .001) and a negative lusitropic effect (decrease in maximum lengthening velocity at preload only and negative peak of the isometric force derivative normalized per cross-sectional area, P < .01 and P < .001 at 50 and 100 microM, respectively). At 100 microM, the decrease in relaxation parameters was more marked than that in contraction parameters under isotonic conditions, as shown by the decrease in the slope of the relationship between peak lengthening velocity and maximum extent of muscle shortening (P < .01); this result reflects an intrinsic negative relaxant effect. No relaxant effect was found under isometric conditions at either concentration. The mechanical effects of low calcium were similar to those of cromakalim 100 microM, which suggests that the drug acted mainly by reducing the cellular calcium entry. Despite the negative mechanical effect of cromakalim, mechanical efficiency was preserved. This could partly explain the cardioprotective effect of cromakalim during ischemia.
测定了50微摩尔和100微摩尔的三磷酸腺苷敏感性钾通道开放剂克罗卡林对豚鼠左心室乳头肌的机械和能量效应，并与低钙浓度下的效应进行比较（每组n = 9）。两种浓度的克罗卡林均诱导负性肌力作用（仅在预负荷下最大缩短速度降低，仅在预负荷下肌肉最大缩短程度降低，50微摩尔和100微摩尔时分别为P <.01和P <.001；等长收缩期每横截面积标准化的最大等长主动力，P <.001；每横截面积标准化的等长力导数的正峰值，P <.001）和负性变松弛作用（仅在预负荷下最大延长速度降低，每横截面积标准化的等长力导数的负峰值，50微摩尔和100微摩尔时分别为P <.01和P <.001）。在100微摩尔时，等张条件下松弛参数的降低比收缩参数更明显，如最大延长速度与肌肉最大缩短程度之间关系的斜率降低所示（P <.01）；这一结果反映了内在的负性松弛效应。在两种浓度下的等长条件下均未发现松弛效应。低钙的机械效应与100微摩尔克罗卡林的效应相似，这表明该药物主要通过减少细胞钙内流起作用。尽管克罗卡林有负性机械效应，但机械效率得以保留。这可能部分解释了克罗卡林在缺血期间的心脏保护作用。
