Local anesthetic and negative chronotropic effects of diltiazem on canine cardiac Purkinje fibers.
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.
Dangman
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KH
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Ziam
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Miura
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D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local; D000818:Animals; D003864:Depression, Chemical; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D000779:Anesthetics, Local; D004110:Diltiazem