Verapamil reduces the arrhythmogenic effect of endothelin.
In a previous study we established that endothelin-1 (ET-1) can induce characteristic ventricular tachycardias (VT) with significant prolongation of QT and QTc time. In this investigation we studied the role of CA2+ channels in the pro-arrhythmic effects of ET-1. In 24 anesthetized, open-chest mongrel dogs, ET-1 was administered into the left anterior descending coronary artery at a comparatively low dose (60 pmol/min) for 30 min. Twelve dogs received the Ca(2+)-channel blocker verapamil (0.4 mg/kg) before ET-1 application. The following parameters were recorded continuously over the infusion period: systemic arterial blood pressure, coronary blood flow, surface ECG leads, epicardial atrial and ventricular electrograms, and right and left ventricular endocardial monophasic action potentials (MAP). Electrophysiologic studies were performed by programmed electrical stimulation of the heart. Blockade of myocardial Ca2+ channels attenuated the arrhythmogenic action of ET-1. After verapamil administration to ET-1-treated dogs, sustained VT did not appear and ventricular fibrillation (VF) developed only in two dogs. In the control group serious and sustained VT and VF developed in nine animals. It is noteworthy that verapamil did not prevent ET-1-induced prolongation of QT time. The results appear to prove that myocardial Ca2+ channels are involved in the proarrhythmic effect of ET-1.
Solti
F
F
Department of Cardiovascular Surgery, Semmelweis University Medical School, Budapest, Hungary.
Tóth
M
M
Merkely
B
B
Kékesi
V
V
Gellér
L
L
Szokodi
I
I
Horkay
F
F
Juhász-Nagy
A
A
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D019332:Endothelin-1; D006439:Hemodynamics / Q000187:drug effects; D014700:Verapamil / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D019332:Endothelin-1; D014700:Verapamil