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European Heart Journal 1992 13(3):395-403;
Copyright © 1992 by the European Society of Cardiology.
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© 1992 The European Society of Cardiology

Effect of cicletanine on reperfusion-induced arrhythmias and myocardial ion contents: a comparison with furosemide

M. KOLTAI, A. TOSAKI, P. BERTHET*, T. TARRADE*, A. ESANU and P. BRAQUET

Institut Henri Beaufour
*IPSEN Paris, France

Received 22 October 1990; revised 26 February 1991; .

Correspondence Dr M. Koltai, Institut Henri Beaufour, 17, avenue Descartes, 92350 Le Plessis Robinson, France

Abstract

We studied the effects of cicletanine, a furopyridine antihypertensive drug, and furosemide, a loop diuretic, on ventricular arrhythmias, such as sustained ventricular fibrillation (VF) and ventricular tachycardia (VT), and myocardial ion content in Langendorff rat hearts subjected to 30min global ischaemia then 10 min reperfusion. Myocardial Na+ K+ Ca2+ and Mg2+ concentrations were measured by washout technique and atomic absorption spectrophotometry before and after ischaemia and reperfusion. Drugs were either perfused (acute treatment) or orally gavaged daily to the rats for 14 days before isolation of their hearts (chronic treatment). Under in vitro conditions 10–5, 3 x 10–5, 10–4 or 3 x 10–4 M of cicletanine reduced the incidence of sustained VF and VT from the control values of 91% and 100% to 83% and 100%, 50% (P<0.05) and 67%, 33% (P<0.01) and 50% (P<0.05), 25% (P<0.01) and 41% (P<0.05), respectively. Chronic treatment with 3, 10,30 or 100 mg. kg–1. day–1 of cicletanine also resulted in a dose-dependent anti-arrhythmic effect. Neither acute (10–5, 3 x 10–5 and 10–5 M) nor chronic furosemide treatment (3, 10 and 30 mg. kg–1. day–1) influenced the incidence of arrhythmias. Acute treatment with cicletanine or furosemide did not change myocardial ion concentrations, in non-ischaemic hearts, while chronic treatment with 30 mg . kg–1 . day–1 furosemide significantly reduced myocardial Na+, K+ and Mg2+ content and increased Ca2+ concentration. Both acute and chronic cicletanine treatments attenuated ischaemia/reperfusion-induced myocardial Na+ and Ca2+ gains and K+ loss, while furosemide did not. Submaximal incidence of arrhythnias were observed after 25 min ischaemia. Under these conditions chronic treatment with 100 mg . kg–1 of cicletanine induced a slight anti-arrhythmic effect whereas 30 mg . kg–1 furosemide was arrhythmogenic. These results indicate that suppression by cicletanine of reperfusion-induced arrhythmias is correlated with the reduction of ischaemia/reperfusion-induced myocardial ion shifts. This effect may be of importance in the clinical management of ischaemic myocardial tissue damage developing as a consequence of sustained arterial hypertension.

Key Words: Ischaemia • reperfusion • arrhythmias • myocardial Na+ • K+ • Ca2+ and Mg2+ • contents • cicletanine • furosemide


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