Low- and medium-dose diltiazem in chronic atrial fibrillation: Comparison with digoxin and correlation with drug plasma levels

Maragno, I; Santostasi, Giovanni; Gaion, R.M.; Trento, Massimo; Grion, A.M.; Miraglia, G; Volta, Sergio Dalla

doi:10.1016/0002-8703(88)90610-2

Cited by 27 publications

(16 citation statements)

References 30 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: 59%

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: 59%

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

et al. 1992

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“…[13][14][15][16][17] As an estimate of left ventricular efficiency (E), we calculated useful work (ie, CO ϫ P Ao ) and divided that product by an estimate of myocardial oxygen demand (ie, HR ϫ P Ao ϫ dP/dt max ). 21 E ഡ (CO ϫ P Ao )/(HR ϫ P Ao ϫ dP/dt max )…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Myocardial oxygen consumption (MVO 2 ) was not measured directly but was estimated by the product of heart rate (HR) and mean systemic arterial pressure (P Ao ), termed the rate-pressure-product (RPP). [13][14][15][16][17] MVO 2 ഡ HR ϫ P AoAlthough the prime determinants of myocardial oxygen consumption are HR, 18 myocardial contractility, 19 and peak tension, 20 RPP is commonly used for clinical studies. [13][14][15][16][17] As an estimate of left ventricular efficiency (E), we calculated useful work (ie, CO ϫ P Ao ) and divided that product by an estimate of myocardial oxygen demand (ie, HR ϫ P Ao ϫ dP/dt max ).…”

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confidence: 99%

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Cardiovascular Effects of Intravenous Diltiazem in Dogs with Iatrogenic Atrial Fibrillation

Miyamoto

Nishijima

Nakayama

et al. 2000

Veterinary Internal Medicne

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Atrial fibrillation (AF) was induced in anesthetized Beagle hounds to determine the dose of diltiazem (D) that resulted in hemodynamic function similar to that observed during sinus rhythm (SR). Dogs were instrumented to record hemodynamic and electrophysiological parameters. Six dogs were given D, IV at cumulative doses of 0.063, 0.188, 0.438, 0.938, and 1.938 mg/kg, whereas 6 other dogs received vehicle in equivalent volumes. Plasma concentrations (PC) of D were measured. A cumulative dose of D between 0.438 and 0.938 mg/kg produced PC of 67.8 to 117.4 ng/mL and resulted in a heart rate (HR) closest to that observed during SR. At doses up to 0.938 mg/kg, no parameter of systolic function fell below that obtained during SR. At a dose of 0.938 mg/kg, the left ventricular end-diastolic and right atrial pressures exceeded those during SR. The rate-pressure product did not differ from that during SR at a dose of 0.938 mg/kg and fell below that during SR at the dose of 1.938 mg/kg. Left ventricular efficiency decreased from SR to AF, returned to values not different from those during SR at a dose of 0.938 mg/kg, and increased to values above those observed during SR at a dose of 1.938 mg/kg. In AF, slowing the HR with 0.438-0.938 mg/kg of D with resultant PC of 67.8-117.4 ng/mL results in cardiovascular function not different from that observed during SR.Key words: Cardiac efficiency; Heart rate.blocks L-type calcium channels, 1 and has proven useful in both humans 1-8 and dogs 9-12 for slowing the ventricular response in patients with atrial fibrillation (AF). Because of the dose-response relationship, it is possible to slow the ventricular rate (ie, response) to almost any degree, even to rates too low to sustain life. Although it is agreed that a ventricular rate of 250/min in a patient with AF is too fast, there is little agreement on what range of ventricular rates minimizes myocardial oxygen consumption and right atrial pressure but sustains cardiac output and systemic arterial pressure at levels appropriate for optimal performance.The purpose of this study is to report the effects of graded doses of D on parameters of cardiovascular function in dogs with AF produced by rapid atrial pacing. Our hypothesis was that D could produce a ventricular pressure (termed optimal) at which the pressure-rate product (the prime determinant of myocardial oxygen consumption) and right atrial pressure are low and systemic arterial pressure is sustained at nearly normal levels (ie, near values obtained during sinus rhythm [SR]). Such a result should optimize ventricular efficiency (ie, the ratio of useful work to myocardial oxygen consumption). Materials and MethodsTwelve, young adult, healthy Beagles of both sexes were anesthetized with thiopental (12 mg/kg IV) and ␣-chloralose a (100 mg/kg IV), and anesthesia was maintained with ␣-chloralose (30 mg/kg/h IV). Dogs were intubated and ventilated with a tidal volume of 12.5 mL/ kg (room air) and at a frequency of 12-15 breaths per minute to sustain PaCO 2 35-45 mmHg. Dogs were pl...

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“…In chronic AF patients 240 mg/day diltiazem combined with digoxin is an effective and safe regimen and enhances digoxin-mediated control of HR both at rest and during exercise [299], [300]. The same combined treatment alleviated the symptoms in 69 % of the patients without changing the digoxin serum level [300] and was superior for control of 24-hour mean HR as compared to each drug used separately [301]. Slow-release formulation of diltiazem (120 mg twice a day) similarly to D600 (100 mg twice a day) and verapamil (120 mg twice a day) reduced peak HRs recorded during a 6-min walking test to similar extent in 18 permanent AF patients without organic heart disease but receiving oral digoxin [262].…”

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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Low- and medium-dose diltiazem in chronic atrial fibrillation: Comparison with digoxin and correlation with drug plasma levels

Cited by 27 publications

References 30 publications

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

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

Cardiovascular Effects of Intravenous Diltiazem in Dogs with Iatrogenic Atrial Fibrillation

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

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