VENTRICULAR TACHYCARDIAS INDUCED BY INTRACORONARY ADMINISTRATION OF ENDOTHELIN-1 IN DOGS

In 12 anesthetized, open-chest mongrel dogs, endothelin-1 (ET-1) was i nfused into the left anterior descending coronary artery through an in dwelling catheter at a dose of 30 pmol . min(-1) for 30 min (n = 8). I n four dogs the ET-1 dose was increased to 60 pmol/min for 10 min. Pro grammed electrical stimulation was used for electrophysiologic studies . Coronary blood flow was reduced by 32% on average without any ischem ic 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 c ases; ventricular extrasystoles, and nonsustained and sustained tachyc ardias occurred and, in 11 cases, ventricular fibrillation terminated the experiments. In two dogs, early afterdepolarization was recorded. Therefore, ET-I is capable of inducing fatal ventricular arrythmias at least partly independent of its vasoconstrictor effect. QT prolongati on appears to have a pathophysiologic role in this arrythmogenic effec t.