Comparison of two calcium antagonists, verapamil and fendiline, in an experimental model of myocardial ischaemia mimicking classical angina on effort

Csik, Vera; Szekeres, L.; Udvary, Éva

doi:10.1111/j.1476-5381.1983.tb10492.x

Cited by 11 publications

(6 citation statements)

References 9 publications

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“…The doses of nicardipine HCI, verapamil (11.0-16.0 kg) were anaesthetised and ventilated artificially; a thoracotomy was performed through the left lateral fifth intercostal space of each animal. The technique used was adapted from that described by Szekeres et al (1976) and Csik et al (1983), using only an electrophysiological indicator at the onset of the post-ischaemic recovery phase to represent oxygen/metabolic debt. Instead of inducing partial obstruction to flow through the mid-region of the left anterior descendingartery (LAD), bymeansofconstricting a flexible cannula system linking autoperfused blood to a femoral or carotid artery, a partially snared ligature was applied.…”

Section: Preparation Of Test Drugsmentioning

confidence: 99%

Nicardipine in models of myocardial infarction.

Bj¹,

Calder²,

Wilson³

1985

Brit J Clinical Pharma

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1 In a dog model of partial myocardial ischaemia, superimposed ST segment elevations in epicardial ECGs were inhibited by nicardipine over a cumulative i.v. dose range of 1-20 ,ug kg-1. 2 Over the cumulative i.v. dose range of 0.5-166.5 ,ug kg-', nicardipine had little overall effect on gross cardiac conduction, at spontaneous heart rate. 3 Dogs that received oral 1-2 mg kg-1 nicardipine daily for 16 weeks and then survived 1 week occlusion of the left anterior descending coronary artery (LAD) developed a superior coronary collateral circulation compared with untreated animals. 4 Nicardipine given by three different dosing schedules to baboons markedly limited myocardial infarction over a 6 h period of LAD occlusion. 5 Compared with a group of completely untreated dogs, there was protection of the myocardium in the animals given nicardipine that survived 3 months occlusion of the LAD.

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Section: Preparation Of Test Drugsmentioning

confidence: 99%

Nicardipine in models of myocardial infarction.

Bj¹,

Calder²,

Wilson³

1985

Brit J Clinical Pharma

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“…In this experiment, BP was controlled at a constant level to avoid disturbance of the coronary action of the com pound due to hypotension. This ischemic heart model mimics, in certain aspects at least, the alterations in myo cardial oxygen demand and supply in classical angina pectoris, and it has been reported to be useful for the evaluation of potential antianginal drugs (9,18). Using a similar model, Szekeres et al (9) found that a 10-min i.v.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Properties of Blood Pressure and Heart Rate Control in Suncus

Isono¹,

Sato²,

Koibuchi³

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-Theanti-ischemic heart effect of (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a novel nitric oxide donor, was studied in dog and rat preparations in vivo and in vitro. In anesthetized dogs with partially occluded coronary artery that were subjected to atrial pacing at a constant blood pressure, FK409 (1-100 pg/kg, i.v.) suppressed the ST-segment elevation on epicardial electrocar diograms. Glyceryl trinitrate (GTN; 10, 32 pig/kg) or dipyridamole (1000 ,ug/kg) failed to suppress the ST segment elevation, although continuous i.v. infusion of GTN (32, 100 pg/kg/min) was effective. FK409 also suppressed the ST-segment elevation induced by methacholine in anesthetized rats by both i.v. (10, 100,ug/kg) and intraduodenal (i.d., 100, 1000 pg/kg) injections, while GTN (100 pg/kg, i.v.; 1000 pg/kg, i.d.) was effective only by the i.v. route. FK409 (0.32 pg/kg/min, i.v.) and GTN (10 pg/kg/min) increased the blood flows of the endomyocardium (ENDO) and the epicardium (EPI) and the flow ratio of ENDO/EPI in the ischemic zone in anesthetized dogs with occluded coronary artery. Furthermore, in isolated dog vascular preparations, FK409 (4.6 x 10-10-4.6 X 10-7 M) had a greater vasorelaxing effect on the large coronary artery [2.0-2.5-mm outer diameter (od)] than on the small coronary artery (0.3-0.5-mm od) or the saphenous artery. The results suggest that FK409 protects against acute experimental myocardial ischemia through relaxation of the large conductive coronary artery, and may be a useful oral drug for the treatment of angina pectoris.

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“…In open-chest anesthetized dogs D600 significantly elevated myocardial blood flow in the non-ischemic area, but did not influence blood flow in the ischemic region [251] in contrast to the effect of verapamil, which either increased CF to the ischemic area [112] or caused a coronary steal from the ischemic area of the myocardium [128]. Ischemia and reperfusion-induced arrhythmias were reduced by D600 in rats [252], dogs [253] and guinea-pigs [254].…”

Section: D600 (Gallopamil) Animal Studies With D600mentioning

confidence: 96%

“…This effect is often not homogenous but a redistribution of the available CF can be seen. In some cases, CF of the ischemic area is increased improving the myocardial oxygen supply/oxygen requirement ratio [112] which is again beneficial. 7.…”

Section: Potential Mechanisms Behind the Antiarrhythmic Actions Of Ccasmentioning

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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Comparison of two calcium antagonists, verapamil and fendiline, in an experimental model of myocardial ischaemia mimicking classical angina on effort

Cited by 11 publications

References 9 publications

Nicardipine in models of myocardial infarction.

Nicardipine in models of myocardial infarction.

Pharmacological Properties of Blood Pressure and Heart Rate Control in Suncus

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

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