Endothelin-1 (ET-1) is a potent vasoconstrictor, and ETA receptors mainly mediate this effect. Elevated plasma levels of ET-1 are observed in patients with coronary heart disease. The release of this peptide from the damaged endothelium may play a role in the initiation and maintenance of myocardial ischaemia. This study examines the ETA receptor-mediated role of endogenous ET-1 in post-ischaemic myocardial function after prolonged hypoperfusion in normal non-failing hearts. In an isolated rat heart model for short-term myocardial hibernation, left ventricular functional recovery after 3h of hypoperfusion (15% of pre-ischaemic flow) followed by 2h of reperfusion was determined. Under steady-state conditions, coronary flow, left ventricular pressure (LVP) and dP/dtmax were measured in the isovolumically beating heart. Additionally, the maximal inotropic response (LVP and dP/dtmax) to calcium stimulation was determined. To study the role of ETA receptors under these pathophysiological conditions, one group was treated with the ETA antagonist BQ 610 (0.8µmol/l) during hypoperfusion, and compared with a control group which received a saline infusion during hypoperfusion. Reperfusion for 2h after 3h of hypoperfusion resulted in partial functional recovery in both groups. Post-ischaemic recovery was significantly better in the hearts that were treated with the ETA antagonist BQ 610 during hypoperfusion (LVP, +19.5% compared with control; dP/dtmax, +13.7% compared with control). The inotropic response to calcium was nearly normalized after ETA blockade. Thus the normal non-failing myocardium profits from ETA receptor blockade during a prolonged period of hypoperfusion, resulting in significantly better post-ischaemic recovery of myocardial function.
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September 2002
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Conference Article|
September 01 2002
ETA receptor blockade improves post-ischaemic functional recovery in ‘hibernating’ rat myocardium
Martin E. BEYER;
*Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
Priv.-Doz. Dr Martin E. Beyer (e-mail [email protected]).
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Marcus FISCHER;
Marcus FISCHER
†Medizinische Klinik, Abt. II, Universität Regensburg, Regensburg, Germany
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Tobias HÖVELBORN;
Tobias HÖVELBORN
*Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
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Hans Martin HOFFMEISTER
Hans Martin HOFFMEISTER
‡Städtisches Klinikum Solingen, Abt. für Kardiologie und Allgemeine Innere Medizin, Solingen, Germany
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 215S–218S.
Citation
Martin E. BEYER, Marcus FISCHER, Tobias HÖVELBORN, Hans Martin HOFFMEISTER; ETA receptor blockade improves post-ischaemic functional recovery in ‘hibernating’ rat myocardium. Clin Sci (Lond) 1 September 2002; 103 (s2002): 215S–218S. doi: https://doi.org/10.1042/CS103S215S
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