PMID: 8587349Jan 1, 1995Paper

Ventricular tachycardias induced by intracoronary administration of endothelin-1 in dogs

Journal of Cardiovascular Pharmacology
M TóthA Juhász-Nagy

Abstract

In 12 anesthetized, open-chest mongrel dogs, endothelin-1 (ET-1) was infused into the left anterior descending coronary artery through an indwelling catheter at a dose of 30 pmol.min-1 for 30 min (n = 8). In four dogs the ET-1 dose was increased to 60 pmol/min for 10 min. Programmed electrical stimulation was used for electrophysiologic studies. Coronary blood flow was reduced by 32% on average without any ischemic ECG signs. QT time (186 +/- 3 ms vs. 218 +/- 6, p < 0.05, and 225 +/- 9, p < 0.05, p < 0.05). Ventricular irritability increased in all cases; ventricular extrasystoles, and nonsustained and sustained tachycardias occurred and, in 11 cases, ventricular fibrillation terminated the experiments. In two dogs, early afterdepolarization was recorded. Therefore, ET-1 is capable of inducing fatal ventricular arrythmias at least partly independent of its vasoconstrictor effect. QT prolongation appears to have a pathophysiologic role in this arrythmogenic effect.

Citations

Oct 13, 2005·Pharmacology & Therapeutics·Sophie MotteRobert Naeije

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