Tetraethylammonium induced coronary spasm in isolated perfused rabbit heart: a hypothesis for the mechanism of coronary spasm.
The vasoactive effect of tetraethylammonium, which is known to reduce potassium conductance of the membrane of arterial smooth muscle cells, was tested on large epicardial coronary arteries in isolated perfused rabbit hearts. These hearts were perfused selectively through the right and left coronary arteries. Left coronary angiography was performed using Krebs-Henseleit solution containing phenolsulfonphthalein under constant pressure, and the epicardial electrogram was recorded. In 59 of 114 hearts 30 mmol.litre-1 tetraethylammonium induced severe constriction of the left epicardial coronary artery, which was associated with electrocardiographic ST segment elevation in some cases. The induced spasm was prevented by diltiazem (200 nmol.litre-1), glyceryl trinitrate (2 mumol.litre-1), or nicorandil (10 mumol.litre-1), but not by phentolamine (1 mumol.litre-1) or atropine (1 mumol.litre-1). In hearts in which tetraethylammonium did not induce spasm, subsequent addition of ergonovine (100 nmol.litre-1) or alkalinisation of the perfusate (pH 7.65-7.70) provoked spasm. The tetraethylammonium induced spasm resembled the coronary spasm seen in patients with variant angina and was a reproducible in vitro model of coronary spasm. These observations support the hypothesis that the primary defect in patients with coronary spasm is decreased potassium permeability of the membrane of coronary arterial smooth muscle cells.
Iwaki
M
M
Second Department of Internal Medicine, School of Medicine, Tokushima University, Japan.
Mizobuchi
S
S
Nakaya
Y
Y
Kawano
K
K
Niki
T
T
Mori
H
H
D000818:Animals; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D003331:Coronary Vessels / Q000473:pathology; D004357:Drug Synergism; D004562:Electrocardiography; D066298:In Vitro Techniques; D010477:Perfusion; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014665:Vasodilator Agents / Q000494:pharmacology
D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019789:Tetraethylammonium