Ventricular tachycardias induced by intracoronary administration of endothelin-1 in dogs.
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.
Tóth
M
M
Cardiovascular Surgical Clinic, Semmelweis University, Medical School, Budapest, Hungary.
Solti
F
F
Merkely
B
B
Kékesi
V
V
Horkay
F
F
Szokodi
I
I
Juhász-Nagy
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D016232:Endothelins / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000139:chemically induced*
D016232:Endothelins