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Milrinone, a newly developed analogue of amrinone, possesses potent positive inotropic effects. Electrophysiologic actions of the drug have thus far been reported in only one study conducted on canine Purkinje fibers. The present study used microelectrode techniques to evaluate the electrophysiologic effects of milrinone on normal and depressed isolated ventricular myocardial fibers. At apparent therapeutic concentrations (0.1-0.2 microgram/ml), milrinone abbreviated action potential duration and refractory period in normal myocardial fibers, but caused no significant changes in any other parameter. At similar concentrations, the drug markedly altered the electrical activity of K+-depolarized preparations, producing an increase in action potential amplitude, duration, and dV/dtmax. Milrinone also restored regenerative activity in K+-inactivated ventricular fibers. The drug exerted important effects on conduction velocity, refractoriness, and reflected reentry generated in fibers mounted in a three-compartment chamber in which the central segment was depressed with an "ischemic" solution. Depending on the initial level of block, the drug concentration, and the segments of the preparation exposed to the drug, milrinone (a) suppressed the arrhythmia, (b) shifted its frequency dependence, or (c) induced reentry. Similar results were obtained in homogeneously depressed fibers. The drug produced no major changes in depolarization-induced automaticity. Thus, in addition to its inotropic actions, milrinone produces important electrophysiologic effects. By restoring or improving conduction through areas of depressed conductivity, the drug may alter the manifestation of arrhythmias. 相似文献
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G P Thomas M Karmazyn A C Zygmunt C Antzelevitch N Narayanan 《British journal of pharmacology》1999,126(7):1531-1533
The antimycotic agent clotrimazole (CLT) is a promising potential therapeutic agent for a variety of diseases including cancer. Although it is known that CLT alters calcium homeostasis in many cell types, its cardiac effects are virtually unknown. We investigated the effects of CLT on L-type calcium current (ICa,L) and action potentials in guinea-pig ventricular myocytes. CLT (5, 25 and 50 microM) inhibited basal ICa,L by 16, 59 and 93%, respectively. The inhibitory effect of CLT was rapid and the peak effect was attained within 3 min. At a concentration of 25 microM, the inhibitory effect of CLT was partially reversible whereas the response to 50 microM CLT persisted following drug withdrawal. CLT abbreviated action potential duration at 50 and 90% of repolarization and suppressed the plateau significantly. These results indicate that CLT may have important cardiac effects at concentrations used to induce the antiproliferative action of the drug. 相似文献
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Is extensive atrial fibrosis in the setting of heart failure associated with a reduced atrial fibrillation burden? 下载免费PDF全文
Alexander Burashnikov PhD Charles Antzelevitch PhD 《Pacing and clinical electrophysiology : PACE》2018,41(10):1289-1297
Atrial fibrillation (AF) affects 10–50% of patients with chronic heart failure (HF) and is associated with poor long‐term prognosis. AF is commonly associated with atrial structural remodeling (ASR), principally characterized by atrial dilatation and fibrosis. However, the occurrence of AF in the full spectrum of ASR encountered in patients with HF is poorly defined. Experimental studies have presented evidence that extensive ASR can be accompanied with a reduced burden of AF, secondary to a prominent depression of atrial excitability. This reduction in AF burden is associated with severe atrial fibrosis rather than with dilatation. Clinical studies of patients with HF point to the possibility that advanced ASR is associated with a less frequent AF occurrence than moderate ASR. Our goal in this review is to introduce the hypothesis that AF is less likely to occur in severe versus moderate atrial ASR in the setting of HF and that it is severe atrial fibrosis‐associated depression of atrial excitability that reduces AF burden. 相似文献
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OBJECTIVE: The present study was designed to examine regional differences in the response of alpha 1 adrenoceptor stimulation in the canine ventricle. METHODS: Standard microelectrode techniques were used to record transmembrane action potentials from epicardial, M cell, and endocardial as well as Purkinje fiber preparations isolated from the canine left ventricle. RESULTS: Phenylephrine (0.1-10 microM+ propranolol 0.2 microM) and methoxamine (1-10 microM) produced dose- and rate-dependent prolongation of action potential duration (APD90) in Purkinje fibers (P < 0.05, at 0.1-10 microM, BCL = 0.5-2 s), but an abbreviation of APD90 in tissues from the M region (P < 0.05, at 10 microM, BCL = 0.5-2 s). At slow pacing rates (> or = 2 s), phenylephrine (1 microM) exerted a small, significant (P < 0.05) prolongation of APD90 in epicardium and endocardium which returned to control values when the concentration was increased to 10 microM. The amplitude of phase 1 of the action potential in M and epicardial cells was significantly increased by phenylephrine at concentrations of 10 microM (P < 0.05). Prazosin (1 microM), a nonspecific alpha 1 antagonist, reversed these effects of phenylephrine (10 microM) and methoxamine (10 microM) on APD90 and the action potential notch. The alpha 1b-antagonist, chloroethylclonidine (0.1-1.0 microM), but not the alpha 1a-antagonist, WB-4101 (0.1-1.0 microM), reversed the APD-abbreviating effect of methoxamine in the M cell. CONCLUSION: Our results demonstrate striking regional differences in the electrophysiological response of the four canine ventricular cell types to alpha 1 adrenergic agonists. Our data provide support for the hypothesis that different adrenoceptor subtypes underlie the opposite response of M cells (alpha 1b-APD abbreviation) and Purkinje fibers (alpha 1a-APD prolongation) to alpha 1-adrenoceptor activation. 相似文献
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Makoto Tomita Hitoshi Kitazawa Masahito Sato Masaaki Okabe Charles Antzelevitch Yoshifusa Aizawa 《Journal of electrocardiology》2012
A 69-year-old man without structural heart disease was admitted for syncope. His electrocardiogram displayed complete right bundle branch (CRBBB). A coved type ST elevation was observed with transient normalization of CRBBB giving rise to a normal QRS. These findings suggest that Brugada syndrome can be masked by CRBBB. 相似文献