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

F. Horkay, L. Gellér, O. Kiss, T. Szabo, H. Vago, V. Kékesi, A. Juhász-Nagy, B. Merkely

Research output: Contribution to journalArticle

10 Citations (Scopus)

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
JournalJournal of Cardiovascular Pharmacology
Volume36
Issue number5 SUPPL. 1
DOIs
Publication statusPublished - 2000

Fingerprint

Endothelin-1
Cardiac Arrhythmias
Arterial Pressure
Dogs
Control Groups
Ventricular Tachycardia
Cardiac Output
bosentan
Endothelin A Receptor Antagonists
Endothelin B Receptor Antagonists
Pericardium
Ventricular Fibrillation
Action Potentials
Electrocardiography
Ischemia

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{b787ac46530e425db8c728458e08f005,
title = "Bosentan the mixed endothelin-A- and -B-receptor antagonist suppresses intrapericardial endothelin-1-induced ventricular arrhythmias",
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.",
keywords = "Bosentan, Endothelin (ET), Monophasic action potential duration (MAPD), Ventricular arrhythmia",
author = "F. Horkay and L. Gell{\'e}r and O. Kiss and T. Szabo and H. Vago and V. K{\'e}kesi and A. Juh{\'a}sz-Nagy and B. Merkely",
year = "2000",
doi = "10.1097/00005344-200000006-00001",
language = "English",
volume = "36",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "5 SUPPL. 1",

}

TY - JOUR

T1 - Bosentan the mixed endothelin-A- and -B-receptor antagonist suppresses intrapericardial endothelin-1-induced ventricular arrhythmias

AU - Horkay, F.

AU - Gellér, L.

AU - Kiss, O.

AU - Szabo, T.

AU - Vago, H.

AU - Kékesi, V.

AU - Juhász-Nagy, A.

AU - Merkely, B.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Bosentan

KW - Endothelin (ET)

KW - Monophasic action potential duration (MAPD)

KW - Ventricular arrhythmia

UR - http://www.scopus.com/inward/record.url?scp=0033734714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033734714&partnerID=8YFLogxK

U2 - 10.1097/00005344-200000006-00001

DO - 10.1097/00005344-200000006-00001

M3 - Article

C2 - 11078409

AN - SCOPUS:0033734714

VL - 36

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 5 SUPPL. 1

ER -