Cardiovascular Effects of Intravenous Diltiazem in Dogs with Iatrogenic Atrial Fibrillation

Abstract

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...

Effects of Enfonidipine Hydrochloride in Dogs with Experimental Supraventricular Tachyarrhythmia

“…Miyamoto et al has reported that although diltiazem hydrochloride slightly lowers the ventricular systolic function of canine SVTA model, the agent could control the ventricular rate. However, as the data were gathered between several minutes and several hours since the beginning of pacing, the decrease in cardiac function caused by SVTA was not clear [18]. On the other hand, Su et al [27] have reported that a decrease in ventricular systolic function had been demonstrated using similar dosage of diltiazem hydrochloride as Miyamoto et al used after 2 to 4 weeks of pacing.…”

“…Suppressive effects of such agents on electrical remodeling are also reported [8]. Consequently, it is expected that T-CC blockers will become a new-type treatment for SVTA in humans [6,18,19,22]. However, there are no clinically available selective T-CC blockers to date.…”