Effect of the calcium antagonist diltiazem on atrioventricular conduction in chronic atrial fibrillation

Theisen, K.; Haufe, M.; Peters, Jochen; Theisen, F.; Jahrmärker, H.

doi:10.1016/0002-9149(85)90307-8

Cited by 25 publications

(6 citation statements)

References 25 publications

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“…[36][37][38][39] These beneficial effects of diltiazem are manifest at doses that produce little change in AV conduction during sinus rhythm and at mean plasma concentrations ranging from 126 to 234 ng/m126'37-39 in the same range as produced by the high dose in the present study. Previous work in dogs suggests that the rate-dependent actions of diltiazem on AV node refractoriness are responsible for its efficacy in experimental models of atrial fibrillation30 and AV reentrant tachycardia.31 The current study shows that the ability of diltiazem to increase AV nodal refractoriness in humans exhibits rate dependency (Figures 3 and 4) measured at both fast and slow cycle lengths ( Figure 7).…”

Section: Potential Significance Of Rate-dependent Actions Of Diltiazesupporting

confidence: 61%

Rate-dependent effects of diltiazem on human atrioventricular nodal properties.

et al. 1992

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Background. Tachycardia enhances the channel-blocking effects of antiarrhythmic drugs. In contrast to the extensive data regarding the rate-dependent effects of sodium channel blockers in humans, little is known about the frequency-dependent effects of calcium channel blockers on human atrioventricular (AV) nodal properties. Accordingly, the purpose of this study was to evaluate the importance of heart rate in modulating the electrophysiological effects of diltiazem in humans.Methods and Results. Electrophysiological studies were performed in 25 patients. Sinus node, atrial, and AV nodal function were evaluated at multiple atrial rates under control conditions and after administration of one of three intravenous doses of diltiazem designed to produce low, intermediate, and high stable plasma concentrations (designated doses 1, 2, and 3, respectively). Results were analyzed in terms of the longest and shortest cycle lengths obtainable in each patient under control and drug conditions. Plasma concentrations of diltiazem were stable and averaged 43+4, 73±6, and 136± 11 ng/ml for doses 1, 2, and 3, respectively. Sinus node recovery time, intra-atrial conduction time, atrial effective refractory period, and HV interval were unaffected by diltiazem infusion. Effects of diltiazem were limited to changes in AV nodal parameters. Stable, dose-dependent increases in Wenckebach cycle length were observed after all three doses of diltiazem (increases of 54±f13, 84±18, and 174±33 msec for doses 1, 2, and 3, respectively). Small nonsignificant increases in AH interval and atrioventricular effective refractory

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Section: Potential Significance Of Rate-dependent Actions Of Diltiazesupporting

confidence: 61%

Rate-dependent effects of diltiazem on human atrioventricular nodal properties.

et al. 1992

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“…However, the structure of RR interval histograms recorded in our experiments were unimodal and skewed to the right as previously reported in spontaneous atrial fibrillation in humans. 14,32,34,36,38 In addition, the characteristics of atrial fibrillation during continuous stimulation were similar to those of atrial fibrillation that persisted after pacing in those experiments in which the arrhythmia persisted long enough to allow analysis. Furthermore, the changes in RR interval histograms that we observed after the administration of diltiazem were very similar to those reported after oral therapy in humans.14,47…”

Section: Discussionmentioning

confidence: 56%

Frequency-dependent effects of diltiazem on the atrioventricular node during experimental atrial fibrillation.

et al. 1989

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Calcium channel blockers depress atrioventricular (AV) nodal properties in vivo in a frequencydependent manner, suggesting that selective drug action during supraventricular arrhythmias may result from use-dependent properties. The present study was designed to examine whether or not the rate-dependent actions of diltiazem account for its therapeutic effects during atrial fibrillation. The determinants of the ventricular response to atrial fibrillation (concealed AV nodal conduction and AV node functional refractory period, AVFRP) were evaluated at multiple cycle lengths (with extrastimulus techniques) and during electrically induced atrial fibrillation (with indirect indexes from RR interval histograms) in anesthetized dogs. In the presence of diltiazem, AVFRP increased progressively relative to control as rate accelerated. At cycle lengths comparable to sinus rhythm in humans, AVFRP increased 10%, 17%, and 32% after doses 1, 2, and 3 of diltiazem, respectively. Drug-induced increases in AVFRP were greater at basic cycle lengths just above the Wenckebach point (17%, 48%, and 81%) and were maximal during atrial fibrillation (39%, 86%, and 154% increases for doses 1, 2, and 3, respectively). Diltiazem also increased the AV conduction system effective refractory period in a frequency-dependent manner without affecting the atrial effective refractory period, thereby increasing the potential zone of concealment into the AV node. Frequency-dependent increases in the zone of concealment were produced by diltiazem and were associated with marked increases in the standard deviation of RR interval histograms during atrial fibrillation (257%, 526%, and 923% increases after doses 1, 2, and 3, respectively). The combination of rate-dependent increases in AVFRP and zone of concealment resulted in a marked amplification of diltiazem's effects during atrial fibrillation, with mean RR interval increases (88%, 200%, and 300% after doses 1, 2, and 3, respectively) that were 8-10 fold greater than increases in AVFRP at cycle lengths comparable to sinus rhythm in humans. We conclude that diltiazem's frequency-dependent effects lead to highly selective depression of AV nodal function during atrial fibrillation. (Circulation 1989;80:380-

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“…These results suggest that S-2150 is a favorable hypotensive agent for hypertensive patients with ischemic heart disease [312]. Diltiazem / once 120 mg or 3x80 mg daily per os lowered VR in patients with AF [296] Diltiazem / 4x60 mg per os reduced the maximal and submaximal HRs during exercise [297] Diltiazem / bolus of either 150 or 300 µg/kg over 2 minutes intravenously converted VT to SR, reduced HR to 100 beats/min [302] Diltiazem / continuous infusion of for 24 h (minimum dose, 0.l reduced the incidence of AF after coronary bypass grafting [305] mg/kg/h) Diltiazem / 0.2 mg/kg intravenously for 3 minutes terminated programmed electrical stimulation induced SVT at high right atrium [310] Clentiazem (TA-3090) / 0.1 mg/kg intravenously for 3 minutes terminated programmed electrical stimulation induced SVT at high right atrium [310] Clentiazem / 80 and 120 mg/day antianginal action in patients with stable angina [311] Clentiazem / 80 and 120 mg/day induced first-degree AV block as a sideeffect in patients with stable angina [311] 9.3. Other CCAs Semotiadil (SD-3211) Animal studies with semotiadil…”

Section: S-2150mentioning

confidence: 89%

“…Moreover, in a study involving 180 patients with rapid AF, low-dose diltiazem (≤ 0.2 mg/kg as a starting intravenous bolus) proved to be as effective as the standard dose of 0.25 mg/kg (according to the 2006 guidelines developed by the American College of Cardiology/American Heart Association/European Society of Cardiology for the management of patients with AF) in adequate rate control but the complication of hypotension was seen significantly less frequently 18 vs. 35 % in low and standard doses, respectively [295]. Oral diltiazem treatment also effectively lowered VR in patients with AF [296] and also reduced the maximal and submaximal HRs during exercise without affecting oxygen uptake, minute ventilation, respiratory exchange ratio or BP [297]. The effects of diltiazem on exercise tolerance are controversial in chronic AF as one study found a modest improvement similarly to that observed with verapamil [229] while another found no benefit in terms of improving either exercise tolerance or CO with either diltiazem or verapamil [228].…”

Section: Anipamil Animal Studies With Anipamilmentioning

confidence: 99%

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

Szentandrássy

Nagy²,

Hegyi³

et al. 2014

CPD

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Cardiac arrhythmias are a major cause of morbidity and mortality in the industrialized world. Among their treatment regimens one can find the calcium channel antagonists (CCAs), the class IV agents. In the cardiovascular system Land T-type calcium channels are found on vascular smooth muscle cells and cardiac myocytes with well defined physiological roles. Inhibition of calcium channels by CCAs has widely been used in clinical practice for several decades. Cardiovascular disorders are one of the many fields of medicine in which CCAs are used for various reasons and conditions. The three main indications of them are hypertension, angina and various cardiac arrhythmias. The most important classes of CCAs are dihydropyridines, phenylalkylamines and benzothiazepines but some newer compounds do not fall into any of these major classes. Dihydropyridines are not used in the antiarrhythmic therapy but are good vasodilators and antianginal agents. In contrast, phenylalkylamines and benzothiazepines exert cardiac actions in vivo and therefore these are one choice of antiarrhythmic drugs. This review focuses on phenylalkylamines, benzothiazepines and on new drugs with potential antiarrhythmic action in the heart as well as the mechanisms how calcium channels antagonism can lead to an antiarrhythmic action.

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Effect of the calcium antagonist diltiazem on atrioventricular conduction in chronic atrial fibrillation

Cited by 25 publications

References 25 publications

Rate-dependent effects of diltiazem on human atrioventricular nodal properties.

Rate-dependent effects of diltiazem on human atrioventricular nodal properties.

Frequency-dependent effects of diltiazem on the atrioventricular node during experimental atrial fibrillation.

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

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