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J Thorac Cardiovasc Surg. 2009 Apr;137(4):1005-11, 1011e1. doi: 10.1016/j.jtcvs.2008.10.037. Epub 2009 Feb 12.

Improved myocardial protection in the failing heart by selective endothelin-A receptor blockade.

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Department of Cardiac Surgery, LK St Poelten, Vienna Medical University, Vienna, Austria.



Ischemia/reperfusion injury caused by cardioplegic arrest is still a major challenge in patients with reduced left ventricular function. We investigated the effect of chronic versus acute administration of the selective endothelin-A receptor antagonist (ERA) TBC-3214Na during ischemia/reperfusion in failing hearts.


Male Sprague-Dawley rats underwent coronary ligation. Three days after myocardial infarction (MI), 19 randomly assigned animals (ERA chronic) were administered TBC-3214Na continuously with their drinking water, 29 MI rats received placebo, and 3 rats died during the observation period. Six weeks after infarction, hearts were evaluated in a blood-perfused working heart model during 60 minutes of ischemia and 30 minutes of reperfusion. In 14 MI rats, TBC-3214Na (ERA acute) was added to the cardioplegic solution during ischemia. Thirteen MI rats served as control.


At a similar infarct size, postischemic recovery of cardiac output (ERA chronic: 91% +/- 10%, ERA acute: 86% +/- 11% vs control: 52% +/- 15%; P < .05) and external heart work (ERA chronic: 90% +/- 10%, ERA acute: 85% +/- 13% vs control: 51% +/- 17%; P < .05) was significantly enhanced in both TBC-3214Na-treated groups whereas recovery of coronary flow was only improved in ERA acute rats (ERA acute: 121% +/- 23% vs ERA chronic: 75% +/- 13%; control: 64% +/- 15%; P < .05). Blood gas measurements showed enhanced myocardial oxygen delivery and consumption with acute TBC-3214Na therapy. Additionally, high-energy phosphates (phosphocreatine) were significantly higher and transmission electron microscopy revealed less ultrastructural damage under acute TBC-3214Na administration.


Acute endothelin-A receptor blockade is superior to chronic blockade in attenuating ischemia/reperfusion injury in failing hearts. Therefore, acute endothelin-A receptor blockade might be an interesting option for patients with heart failure undergoing cardiac surgery.

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