Bosentan the mixed endothelin-A- and -B-receptor antagonist suppresses intrapericardial endothelin-1-induced ventricular arrhythmias

F. Horkay, L. Geller, O. Kiss, T. Szabo, H. Vago, V. Kekesi, A. Juhasz-Nagy, B. Merkely

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Abstract

In earlier studies severe ventricular arrhythmias developed during intrapericardial (i.p.) endothelin-1 (ET-1) infusion. Monophasic action potential duration (MAPD90) increase and significant ST segment elevation preceded the onset of arrhythmias. The aim of this study was to test the antiarrhythmic and anti-ischemic efficacy of the mixed endothelin-A- and -B- (ET(A)/(B))) receptor antagonist bosentan (BOS) on ET-1-induced arrhythmias on six mongrel dogs. Ten minutes after an intravenous bolus dose of BOS (10 mg/kg), ET-1 (33 pmol/kg/min) was given into the pericardial space for 30m in (BOS group). Six control dogs received only ET-1 infusion (control group). Mean arterial blood pressure (MAP), cardiac output, electrocardiograph (ECG), right and left ventricular endo- and epicardial (RVEND, RVEP, LVEND, LVEP) MAPD90S were recorded. MAP and cardiac output did not change significantly in the BOS group. Significant MAPD90 prolongation was found in all investigated regions of the control group (ET start vs ET 20 min: LVEP, 174 ± 3 vs 208 ± 10; RVEND, 206 ± 9 vs 241 ± 12* ms, *p < 0.05), while significant MAPD90 alterations were not observed in the BOS group (basic vs ET 20 min: RVEP, 189 ± 5 vs 196 ± 5; LVEP, 199 ± 5 vs 199 ± 4; RVEND, 194 ± 5 vs 195 ± 6; LVEND, 209 ± 3 vs 213 ± 5 ms). Early afterdepolarizations (EADs) were observed in three control dogs. Severe ventricular arrhythmias [incessant nonsustained ventricular tachycardias (nsVTs) in all cases, sustained VTs (sVTs) in four, ventricular fibrillation (VF) in two instances] were present in the control group, whereas nsVTs were observed only in two dogs in the BOS group. ST segment elevation was more pronounced in the control group than in the BOS group (1.01 ± 0.2 vs 0.41 ± 0.07 mV, p < 0.05). In summary, bosentan effectively inhibits intrapericardial ET-1-induced ventricular arrhythmias, moreover it may have a protective effect against epimyocardial ischemia.

Original languageEnglish
Pages (from-to)S320-S322
JournalJournal of cardiovascular pharmacology
Volume36
Issue number5 SUPPL. 1
DOIs
Publication statusPublished - Jan 1 2000

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Keywords

  • Bosentan
  • Endothelin (ET)
  • Monophasic action potential duration (MAPD)
  • Ventricular arrhythmia

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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