Dangman K H, Ziam S, Miura D S
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Am Heart J. 1989 Jun;117(6):1271-7.
The electrophysiologic effects of diltiazem, a drug with antianginal, antihypertensive, and antiarrhythmic actions, were studied on transmembrane action potentials recorded from isolated canine cardiac tissues by means of standard microelectrode techniques. Recordings were made from normal canine cardiac Purkinje fibers in major false tendons, from normal Purkinje fibers partially depolarized by treatment with Tyrode's solution containing 7 mmol/L potassium chloride, from subendocardial Purkinje fibers of the left ventricle of normal hearts, and from subendocardial ventricular muscle preparations. Diltiazem, 1 and 2 mumol/L, exerted local anesthetic effects and decreased the action potential plateau duration in normal Purkinje fibers. In contrast, diltiazem, 1 mumol/L, did not affect the action potentials of potassium-depolarized Purkinje fibers, subendocardial Purkinje fibers, or ventricular muscle cells. Diltiazem, 1 and 2 mumol/L, did not decrease normal or high potential automaticity or catecholamine-enhanced high potential automaticity in canine Purkinje fibers with maximum diastolic potentials greater than -80 mV. In contrast, diltiazem, 1 mumol/L, rapidly terminated low potential automaticity in barium-treated Purkinje fibers with maximum diastolic potentials of -40 to -60 mV. The local anesthetic effects of diltiazem, as well as the effect on low potential automaticity, can explain the antiarrhythmic effects of the drug.
地尔硫䓬是一种具有抗心绞痛、抗高血压和抗心律失常作用的药物，利用标准微电极技术，研究了其对从离体犬心脏组织记录的跨膜动作电位的电生理效应。记录取自主要假腱索中的正常犬心脏浦肯野纤维、用含7 mmol/L氯化钾的台氏液处理后部分去极化的正常浦肯野纤维、正常心脏左心室的心内膜下浦肯野纤维以及心内膜下心室肌标本。1和2 μmol/L的地尔硫䓬具有局部麻醉作用，并缩短了正常浦肯野纤维的动作电位平台期。相比之下，1 μmol/L的地尔硫䓬对钾去极化的浦肯野纤维、心内膜下浦肯野纤维或心室肌细胞的动作电位没有影响。1和2 μmol/L的地尔硫䓬不会降低最大舒张电位大于 -80 mV的犬浦肯野纤维的正常或高电位自律性或儿茶酚胺增强的高电位自律性。相反，1 μmol/L的地尔硫䓬能迅速终止最大舒张电位为 -40至 -60 mV的钡处理浦肯野纤维的低电位自律性。地尔硫䓬的局部麻醉作用以及对低电位自律性的作用可以解释该药物的抗心律失常作用。
