Propofol-Induced Vasodilation in Human Internal Mammary Artery: Role of Potassium Channels

Abstract

Objectives: The aim of this study was to investigate the vascular effects and mechanisms of propofol in the human internal mammary artery (MA).

Design: In vitro experimental study.

Setting: The study was conducted in the research laboratory of a pharmacology department.

Participants: IMA segments were obtained from 52 patients undergoing coronary artery bypass surgery.

Interventions: The IMA rings were suspended in isolated organ baths, and the changes in the tension were isometrically recorded. The antagonistic effect of propofol (1 mu M, 10 mu M, and 100 mu M) on contractions induced by potassium chloride (45 mM), phenylephrine (1 mu M), 5-hydroxytryptamine (30 mu M), and calcium chloride (10 mu M-10 mM) was investigated. The relaxations induced by propofol also were tested in the presence of the nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (100 mM); the cyclooxygenase inhibitor, indomethacin (10 mM); and the potassium ion channel inhibitors, tetraethylammonium (1 mM), iberiotoxin (20 nM), glibenclamide (10 mu M), 4-aminopyridine (1 mM), and barium chloride (30 mu M).

Measurements and Main Results: Propofol caused a significant concentration-dependent vasorelaxation, which was endothelium independent. It inhibited the contractions induced by potassium chloride, phenylephrine, 5-hydroxytryptamine, and calcium chloride (p < 0.001), but it did not affect the basal tension. Propofol-induced relaxation was significantly inhibited by iberiotoxin and tetraethylammonium (p < 0.001); however, it was not affected by 4-aminopyridine, glibenclamide, and barium chloride.

Conclusion: This study clearly reveals that propofol relaxes the IMA, and propofol-induced vasodilation may be related to large conductance calcium ion-activated potassium ion channel activation. Propofol use in coronary artery bypass surgery can be valuable via its favorable vasodilator effect to overcome perioperative vasospasm of IMA. (C) 2018 Elsevier Inc. All rights reserved.