Selective stimulation of the parasympathetic preganglionic nerve fibres in the excised and blood-perfused SA node preparation of the dog

Kubota, Katsumi; Hashimoto, Koroku

doi:10.1007/bf00500646

Cited by 81 publications

(33 citation statements)

References 8 publications

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“…The SA node preparation was essentially the right atrium. The preparation was perfused through the cannulated RCA with arterial blood at a constant pressure of about 100 mmHg (Kubota and Hashimoto 1973). Sinus rate was measured with a cardiotachometer (1321, San-ei Instrument, Tokyo) triggered by a bipolar electrograms obtained from the SA node area.…”

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confidence: 99%

Cardiovascular profile of AN-132, a new diamine derivative antiarrhythmic agent, revealed in the isolated, blood-perfused dog heart.

Gotanda

Satoh

Taira

1988

Tohoku J. Exp. Med.

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Profile of AN-132, a New Diamine Derivative Antiarrhythmic Agent, Revealed in the Isolated, BloodPerfused Dog Heart. Tohoku J. exp. Med., 1988, 156 (1), 65-78 -The cardiac and coronary effects of AN-132, a new antiarrhythmic agent, were investigated in isolated, blood-perfused atrioventricular (AV) node, sinoatrial (SA) node and papillary muscle preparations of dogs. AN-132 was administered intraarterially. In AV node preparations, whether injected into the anterior septal artery (ASA ; supplying the His-Purkinje-ventricular system) or the posterior septal artery (PSA ; supplying the AV node), AN-132 prolonged AV conduction time and produced second-or third-degree AV block at large doses in some preparations. Moreover, only when injected into the ASA AN-132 produced a broadening and diminution of amplitude of bipolar electrograms obtained from the right bundle branch and the ventricular septum. In SA node preparations, AN-132 decreased sinus rate and produced atrial standstill at large doses in some preparations. In paced papillary muscle preparations, AN-132 reduced the force of contraction. In spontaneously beating papillary muscle preparations, AN-132 decreased the rate of automaticity and the force of contraction. In all preparations, AN-132 produced a transient increase in blood flow only at large doses. The order of potencies of AN-132 based on the doses that produced 15% suppressions of the above cardiovas cular variables was as follows : cardiac muscle contraction>ventricular automaticity?intraventricular conduction>AV nodal conduction coronary blood flow> SA nodal automaticity. -AN-132 ; antiarrhythmic agent ; AV nodal conduction ; intraventricular conduction ; negative inotropy AN-132 (Fig. 1), a newly synthesized antiarrhythmic agent, has been reported to be effective in several animal models of cardiac arrhythmias, whether given

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confidence: 99%

Cardiovascular profile of AN-132, a new diamine derivative antiarrhythmic agent, revealed in the isolated, blood-perfused dog heart.

Gotanda

Satoh

Taira

1988

Tohoku J. Exp. Med.

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“…This means that eperisone might inhibit the release of ACh by parasympathetic stimulation from nerve endings, in addition to its temporal atropine-like action. In the blood-perfused sinoatrial node preparation, the release of ACh elicited by direct electrical stimulation mainly results from excitation of parasym pathetic preganglionic fibers as reported pre viously (6,18,19). Recently, Noma et al (2) reported that iontophoretic application of eperisone in lower doses of 25 100 nA pro duced a dose-dependent inhibition of spike generation upon electrical nerve stimulation with little effect on the spike height, while a higher dose of 200 nA reduced the spike height in the vestibular nucleus neurons.…”

Section: Discussionmentioning

confidence: 99%

Anti-Nicotinic and Anti-Muscarinic Actions of Eperisone in the Isolated Canine Atrium.

et al. 1991

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ABSTRACT-The effects of eperisone, an antispastic agent, on the chronotropic and inotropic responses to acetylcholine, nicotine or stimulation of intracardiac autonomic nerves were evaluated in isolated, blood-perfused canine atrium. Eperisone (10-300,ug) injected into the sinus node artery of the isolated atrium produced dose-related nega tive chronotropic and inotropic effects, which were not affected by atropine. In the same doses, eperisone inhibited the negative chronotropic and inotropic responses to an injection of acetylcholine and intracardiac parasympathetic stimulation. Eperisone also suppressed the negative followed by positive cardiac responses to nicotine, but did not modify the positive responses to intracardiac sympathetic stimulation or nor epinephrine. The inhibitory effect persisted much longer for the responses to nicotine or parasympathetic stimulation than for those to acetylcholine. These results suggest that eperisone at doses that induce direct cardiac depressant effects exerts its blocking action on nicotinic receptors at parasympathetic ganglia and sympathetic nerve termi nals and on muscarinic receptors at the effector cells in the dog heart.

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“…The hearts were excised from mongrel dogs of either sex weighing 8-14 kg. The isolated, blood-perfused papillary muscle and sino-atrial node preparations were prepared according to the methods of Endoh and Hashimoto (1970)7) and Kubota and Hashimoto (1973), 8) respectively. The preparations were cross-circulated through the cannulated arteries with blood from a donor dog anesthetized with sodium pentobarbital and receiving heparin.…”

Section: Methodsmentioning

confidence: 99%

Studies on positive inotropic agents. IV. Synthesis of 5-(3-amino-2-hydroxypropoxy)-3,4-dihydro-8-hydroxy-2(1H)-quinolinone derivatives.

Tominaga

Ogawa

et al. 1987

CHEMICAL & PHARMACEUTICAL BULLETIN

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Many 5-(3-amino-2-hydroxypropoxy)-3,4-dihydro-8-hydroxy-2(1H)-quinolinone derivatives were synthesized and examined for positive inotropic activity on the canine heart. These compounds were prepared by the reaction of 8-alkoxy-5-(2,3-epoxypropoxy)-2(1H)-quinolinone derivatives and various amines. Among them, 3,4-dihydro-8-hydroxy-543-(1,1,3,3-tetramethylbutylamino)propoxy]-2(1H)-quinolirrone hydrochloride (IIIf) was found to have potent positive inotropic activity with a relatively minor increase in heart rate. Keywordscongestive heart failure; positive inotropic agent; 3,4-dihydro-8-hydroxy-543-(1,1,3,3-tetramethylbutylamino)propoxy]-2(1H)-quinolinone; biological activityWe have been attempting to find positive inotropic agents among compounds bearing a 2(1H)-quinolinone nucleus as candidate drugs for the treatment of congestive heart failure. In the course of our studies, we found that various 2(1H)-quinolinone derivatives showed desirable activity.1,2) We also found that 5-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydro-8-hydroxy-2(1H)-quinolinone (8-OH-carteolol) increased cardiac contractile force.3) Here we report the syntheses and biological activities on the canine heart of many 8-OHcarteolol derivatives.Various 5-(3-amino-2-hydroxypropoxy)-3,4-dihydro-8-hydroxy-2(1H)-quinolinone derivatives (III) were synthesized from the epoxide (I)4) by treatment with appropriate amines, followed by hydrolysis of the tetrahydropyranyloxy group (Table I). Treatment of I with methyl iodide in the presence of NaH in dimethyl formamide (DMF) gave 5-(2,3-epoxypropoxy)-3,4-dihydro-1 -methyl-8-(2-tetrahydropyranyloxy)-2(1H)-quinolinone (IV). The 1-methyl derivative (V) was obtained from IV in the same manner as described for the synthesis of III.The 8-benzyloxy derivative (II)4) was converted to 8-benzyloxy-5-(2,3-epoxypropoxy)-2(1H)-quinolinone (VI) by dehydrogenation with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in dioxane. Compound VI was reacted with butylamine in methanol, followed by hydrogenolysis of the benzyloxy group over 10% palladium on charcoal to afford the desired 2(1H)-quinolinone (VII) (Chart 1).Treatment of 3,4-dihydro-5-hydroxy-8-methoxy-2(1H)-quinolinone (VIII)5) with epichlorohydrin followed by reaction with benzylamine gave the quinolinone (XI). Reaction of the 5-acetoxy derivative (IX)4) with 1-bromo-3-chloropropane in methanol in the presence of K2CO3 gave the corresponding chloride (X). 5-(3-Benzylaminopropoxy)-3,4-dihydro-8-hydroxy-2(1H)-quinolinone hydrochloride (XII) was prepared by reaction of X with benzylamine in acetonitrile (Chart 2).

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Selective stimulation of the parasympathetic preganglionic nerve fibres in the excised and blood-perfused SA node preparation of the dog

Cited by 81 publications

References 8 publications

Cardiovascular profile of AN-132, a new diamine derivative antiarrhythmic agent, revealed in the isolated, blood-perfused dog heart.

Cardiovascular profile of AN-132, a new diamine derivative antiarrhythmic agent, revealed in the isolated, blood-perfused dog heart.

Anti-Nicotinic and Anti-Muscarinic Actions of Eperisone in the Isolated Canine Atrium.

Studies on positive inotropic agents. IV. Synthesis of 5-(3-amino-2-hydroxypropoxy)-3,4-dihydro-8-hydroxy-2(1H)-quinolinone derivatives.

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