Fairhurst A S, Wickie G, Peabody T
Arch Int Pharmacodyn Ther. 1982 Mar;256(1):59-75.
The anti-hyperlipidemic drug clofibrate produces negative inotropic effects and arrythmias in isolated perfused rabbit heart Langendorff preparations. In electrically stimulated rat left atria, clofibrate produces negative inotropic effects, the speed of onset and extent of which are decreased by raising the Ca concentration of the bathing medium. Sensitivity of isolated rat atria to clofibrate is not increased when the tissues are stimulated under slow Ca channel conditions, in which the tissues are activated by either isoproterenol or dibutyryl cyclic AMP, although sensitivity to clofibrate is decreased when atria are exposed to increasing concentrations of norepinephrine. Increasing the stimulation frequency of isolated guinea-pig atria to produce a positive treppe also decreases the inhibitory effect of clofibrate, while in rat atria the typical negative treppe is altered towards a positive treppe in presence of clofibrate. The effects of paired electrical stimulation are not diminished by the drug, suggesting that Ca release from the sarcoplasmic reticulum is not affected by clofibrate, although the drug inhibits the rate of Ca uptake by isolated cardiac sarcoplasmic reticulum and mitochondria. These results suggest that clofibrate has multiple effects on Ca functions in cardiac muscle.
抗高血脂药物氯贝丁酯在离体灌注兔心脏Langendorff标本中可产生负性肌力作用和心律失常。在电刺激的大鼠左心房中，氯贝丁酯产生负性肌力作用，通过提高灌流液中的钙浓度可降低其起效速度和作用程度。当在慢钙通道条件下刺激组织时，即通过异丙肾上腺素或二丁酰环磷腺苷激活组织时，离体大鼠心房对氯贝丁酯的敏感性并未增加，尽管当心房暴露于浓度不断增加的去甲肾上腺素时，对氯贝丁酯的敏感性会降低。增加离体豚鼠心房的刺激频率以产生正阶梯现象也会降低氯贝丁酯的抑制作用，而在大鼠心房中，在氯贝丁酯存在的情况下，典型的负阶梯现象会转变为正阶梯现象。氯贝丁酯不会减弱成对电刺激的作用，这表明肌浆网的钙释放不受氯贝丁酯的影响，尽管该药物会抑制离体心肌肌浆网和线粒体对钙的摄取速率。这些结果表明氯贝丁酯对心肌中的钙功能具有多种作用。
