1. Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model
- Author
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Damian MacDonald, Susanne Bährle, Levente Fazekas, Nicole Stumpf, Siegfried Hagl, Christian F. Vahl, and Gábor Szabó
- Subjects
Endothelin Receptor Antagonists ,Male ,Nitroprusside ,medicine.medical_specialty ,Time Factors ,Endothelium ,Physiology ,medicine.medical_treatment ,Vasodilator Agents ,Ischemia ,Vasodilation ,Myocardial Reperfusion Injury ,Peptides, Cyclic ,Ventricular Function, Left ,Reperfusion therapy ,Piperidines ,Physiology (medical) ,Internal medicine ,Coronary Circulation ,medicine ,Animals ,Heart transplantation ,Endothelin-1 ,business.industry ,Hemodynamics ,medicine.disease ,Receptor, Endothelin A ,Endothelin 1 ,Receptor, Endothelin B ,Acetylcholine ,Rats ,Transplantation ,medicine.anatomical_structure ,Rats, Inbred Lew ,Anesthesia ,cardiovascular system ,Cardiology ,Heart Transplantation ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,Reperfusion injury ,Oligopeptides - 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 =12 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 1 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
- Published
- 1998