Effects of OPC‐8212, a new positive inotropic agent, on canine ventricular arrhythmias

Hashimoto, Keitaro; Mitsuhashi, Harumi

doi:10.1111/j.1476-5381.1986.tb16266.x

Cited by 17 publications

(17 citation statements)

References 12 publications

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“…For intravenous infusion studies, a constant-rate infusion was performed for 10 minutes using a syringe pump, and arterial blood samples were drawn from one lumen of the arterial double-lumen cannula at 0, 1, 3,5,7,9,13,15,30, and 60 minutes after the start of the infusion. [6][7][8]12,14,17,18,[20][21][22][23][24][25][26][27][28][29][30][31][32], female beagle dogs, weighing about 7-12 kg, were anesthetized initially with intravenous thiopental sodium, 30 mg/kg, and intubated. The chest was opened and a two-stage coronary ligation of the left anterior descending artery (LAD) was performed under halothane anesthesia.…”

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confidence: 99%

Effects of antiarrhythmic drugs on canine ventricular arrhythmia models: Which electrophysiological characteristics of drugs are related to their effectiveness?

Hashimoto

Haruno

Matsuzaki

et al. 1991

Cardiovasc Drug Ther

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In order to compare and clarify the effects of various antiarrhythmic drugs when given as monotherapy, we reevaluated our previous data on antiarrhythmic drugs and recalculated antiarrhythmic plasma concentrations of drugs for several canine arrhythmia models. We used three spontaneously occurring arrhythmias: a) digitalis-, b) two-stage coronary ligation-, and c) adrenaline-induced arrhythmias. All antiarrhythmic drugs of class I suppressed digitalis arrhythmia, and, except for lidocaine, also suppressed coronary ligation arrhythmia. Class II antiarrhythmic drugs, beta blockers, and class IV antiarrhythmic drugs, Ca antagonists, had common features of effectiveness and suppressed adrenaline arrhythmia in relatively low concentrations. Class III drugs were not effective on these three arrhythmias. Differences among the antiarrhythmic effects of class I drugs could not be explained by their subclassification based either on action potential duration or kinetic properties of dissociation or association with Na channels. New triggered arrhythmia models in vivo and in vitro canine hearts were developed, and drug effects were not the same as those on the three spontaneously occurring arrhythmia models.

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confidence: 99%

Effects of antiarrhythmic drugs on canine ventricular arrhythmia models: Which electrophysiological characteristics of drugs are related to their effectiveness?

Hashimoto

Haruno

Matsuzaki

et al. 1991

Cardiovasc Drug Ther

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“…Furthermore, despite the fact that other agents have more prominent hemodynamic actions in patients with congestive heart failure, this improvement has not been uniformly associated with a reduction in ventricular arrhythmias and the incidence of sudden cardiac death [9]. In this manner, the possibility that the administration of OPC-8212, a drug with a novel mechanism of action and less potent hemodynamic changes, may improve the ventricular arrhythmia profile and the susceptibility to ventricular tachycardia [27], warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

OPC-8212 in the treatment of congestive heart failure: Results of a pilot study

Kubo

Rector

Strobeck

et al. 1988

Cardiovasc Drug Ther

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To characterize the effects of OPC-8212, a quinolone inotropic agent, in patients with heart failure, we utilized invasive hemodynamics, exercise testing, 24-hour ambulatory electrocardiograms, and two patient self-assessment questionnaires, before and after 1 month of treatment with OPC-8212, in 17 patients with moderate to severe congestive heart failure. There were no significant changes from baseline in heart rate (83 +/- 8 beats/min), mean arterial pressure (70 +/- 15 mmHg), pulmonary wedge pressure (18 +/- 7 mmHg), or cardiac index (2.3 +/- 0.4 L/min/m2) following treatment with OPC-8212. Both exercise duration (5.3 +/- 1.6 min) and peak oxygen consumption (12.0 +/- 2.9 mL/kg/min) were unchanged by OPC-8212. Two independent patient self-assessment scores, the Sickness Impact Profile and the Minnesota Living with Heart Failure Questionnaire, showed improvements from 6.8 to 5.4 and 49 to 38, respectively (both p less than .05), suggesting that the patients reported an improvement in daily functioning. The median ventricular premature contraction count and frequency were reduced from 1,118 beats to 243 beats (p less than 0.05) and 11/1,000 beats to 2.4/1,000 beats (0.05 less than p less than 0.10), respectively. Two patients developed agranulocytosis during longer-term treatment following this 1-month study. These data demonstrate that OPC-8212 did not have significant effects on hemodynamics or exercise tolerance. However, the improvement in patient self-assessment scores and the trend for improvement in ventricular arrhythmia profiles suggest that OPC-8212 may have some benefit for patients with congestive heart failure, but additional placebo-controlled, double-blind studies are necessary.

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“…The practical importance of this result is that this new positive inotropic agent can be used in combination with digitalis without increasing the risk of arrhythmia, and this is a common observation among new positive inotropic drugs in our previous study (6). In the present in vitro electrophysiological study of OPC-18790, it slightly shortened IVCT of the canine iso lated blood-perfused PM preparation, which is a unique effect but is probably not related to the drug effect on the Na channels.…”

Section: Discussionmentioning

confidence: 99%

“…The 1-3 mg/kg OPC-18790 did not aggravate digitalis and two-stage coronary ligation VTs; the maximum tolerable dose for adrenaline VT was 0.3 mg/kg. In our previous study (6), vesnarinone up to 3 mg/kg did not aggravate digitalis VT, but aggravated adrenaline VT, and the maxi mum tolerable dose for adrenaline VT was 0.5 mg/kg. Also 3 mg/kg amrinone and sulmazole did not aggravate digitalis VT, but the maximum tolerable dose for adrena line VT was 1 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Effects of OPC-18790, a New Positive Inotropic Agent, on Canine Ventricular Arrhythmias

Zhenjiu

Awaji

Abe

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-OPC-18790is a positive inotropic and vasodilating agent that increases intracellular cyclic AMP and stimulates Ca currents. We examined its direct electrophysiological effects in isolated blood-per fused canine cardiac preparations. OPC-18790 caused an acceleration of the intraventricular conduction in association with an increase of the contractile force and the coronary blood flow. We also examined the effects of OPC-18790 on ventricular arrhythmias in canine ventricular tachycardia (VT) models. OPC-18790 in doses producing submaximal inotropic effects, 3 mg/kg, i.v., increased the total heart rate, atrial rate and decreased the blood pressure, but did not suppress or aggravate 24 and 48-hr coronary ligation VTs. OPC 18790 up to 3 mg/kg, i.v. also did not suppress or aggravate digitalis-induced VTs. However, this dose of OPC-18790 aggravated halothane-adrenaline induced VT into ventricular fibrillation and eventually death, but a lower dose of 0.3 mg/kg did not aggravate this VT. These results in canine VTs indicate that OPC 18790 is similar to other positive inotropic agents, vesnarinone, amrinone, milrinone and sulmazole. The absence of an aggravating effect of this new positive inotropic agent on digitalis and coronary ligation VTs may be advantageous in a clinical setting of combined therapy with digitalis for myocardial ischemia.

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Effects of OPC‐8212, a new positive inotropic agent, on canine ventricular arrhythmias

Cited by 17 publications

References 12 publications

Effects of antiarrhythmic drugs on canine ventricular arrhythmia models: Which electrophysiological characteristics of drugs are related to their effectiveness?

Effects of antiarrhythmic drugs on canine ventricular arrhythmia models: Which electrophysiological characteristics of drugs are related to their effectiveness?

OPC-8212 in the treatment of congestive heart failure: Results of a pilot study

Effects of OPC-18790, a New Positive Inotropic Agent, on Canine Ventricular Arrhythmias

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