Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model

G. Szabó, Levente Fazekas, Susanne Bährle, Damian MacDonald, Nicole Stumpf, Christian F. Vahl, Siegfried Hagl

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective: Previous studies suggested that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia/reperfusion injury. This study was designed to investigate the effects of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia in a heterotopic rat heart transplantation model. Methods: Isogenic intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of cold ischemic preservation reperfusion was started either after application of placebo (control), BQ123 (3 μmol/kg/min), BQ788 (3 μmol/kg/min), ET-1 (8 pmol/kg/min) or simultaneous infusion of BQ123 or BQ788 and ET-1, respectively (n = 1.2. each). An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Myocardial blood flow (MBF) was assessed by the hydrogen-clearance method. Measurements were taken after I and 24 h of reperfusion. Endothelium-dependent vasodilation to acetylcholine (ACH) and endothelium-independent vasodilation to sodium nitroprusside were also determined. Results: Both BQ123 and BQ788 significantly improved myocardial and endothelial functional recovery during early reperfusion, whereas ET-1 significantly impaired myocardial and endothelial function. Simultaneous infusion of ET-1 diminished the effects of BQ123 and BQ788. Although myocardial function and baseline MBF were similar in all groups after 24 h of reperfusion, endothelium dependent vasodilation to ACH was still significantly higher in the BQ123 and BQ788 groups and lower in the ET-1 groups (p

Original languageEnglish
Pages (from-to)683-690
Number of pages8
JournalCardiovascular Research
Volume39
Issue number3
DOIs
Publication statusPublished - Sep 1 1998

Fingerprint

Endothelins
Endothelin-1
Heart Transplantation
Reperfusion
Ischemia
Vasodilation
Endothelium
Acetylcholine
Heterotopic Transplantation
Myocardial Reperfusion Injury
Nitroprusside
Reperfusion Injury
Myocardial Ischemia
BQ 788
cyclo(Trp-Asp-Pro-Val-Leu)
Hydrogen
Placebos
Pressure

Keywords

  • Endothelin-antagonist
  • Rat
  • Repeffusion
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model. / Szabó, G.; Fazekas, Levente; Bährle, Susanne; MacDonald, Damian; Stumpf, Nicole; Vahl, Christian F.; Hagl, Siegfried.

In: Cardiovascular Research, Vol. 39, No. 3, 01.09.1998, p. 683-690.

Research output: Contribution to journalArticle

Szabó, G. ; Fazekas, Levente ; Bährle, Susanne ; MacDonald, Damian ; Stumpf, Nicole ; Vahl, Christian F. ; Hagl, Siegfried. / Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model. In: Cardiovascular Research. 1998 ; Vol. 39, No. 3. pp. 683-690.
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