Coronary vasomotor disorders during hypoxia-reoxygenation: do calcium channel blockers play a protective role?

Abstract

During heart surgery, myocardial dysfunction may occasionally appear when extracorporeal circulation is discontinued, causing serious haemodynamic disorders. Many mechanisms are involved in this hypoxia-reoxygenation syndrome. The aim of this experimental study was to characterize the vasomotor disorders that take place in the isolated porcine coronary artery during in vitro hypoxia-reoxygenation and to analyse the effect of nifedipine on them. Rings of porcine coronary artery were placed in an organ chamber connected to a system that recorded isometric forces. The vascular rings were divided into two groups: control group (no nifedipine) and study group (nifedipine, 10(-6) mol/l). The vascular rings were precontracted with 30 mmol/l KCl and then hypoxia-reoxygenation was induced. Control arterial rings showed important changes in coronary vasomotor tone: severe hypoxic contraction (from 14.48+/-1.16 g of stable contraction to 17.6+/-0.44 g after the imposition of hypoxia), and transient vasodilation during reoxygenation (69.9+/-10.1% of the maximum contraction achieved). The nifedipine group experienced a slow, progressive, vasodilation throughout the whole experiment (73+/-3.5% of the maximum contraction). Neither hypoxic vasospasm nor fluctuations of the coronary vascular tone occurred. Thus, at the end of the hypoxia, the control vessels presented a degree of contraction similar to the initial level. However, in the rings treated with nifedipine, the percentage of dilation was 73+/-3.5% (P<0.05). In the isolated porcine coronary artery with intact endothelium undergoing a situation of hypoxia-reoxygenation, we have detected transient vasoconstriction during the first period of hypoxia, followed by vasodilation during reoxygenation. The intracoronary administration of nifedipine prior to the imposition of hypoxia prevents hypoxic contraction, achieving a greater and more stable degree of coronary vasorelaxation during the complete process of hypoxia-reoxygenation.

Role of myocardium and endothelium in coronary vascular smooth muscle responses to hypoxia

“…endothelial cells; smooth muscle cells; cardiomyocytes; ATPsensitive potassium channels; adenosine SEVERAL INVESTIGATORS (1,2,4,6,10,20,21,27) have shown in isolated whole heart preparations that hypoxia (lowering the PO 2 in the perfusion solution) induces vasodilation in the whole heart. However, it is not clear whether or not mediators of hypoxia-induced vasodilation originate from vascular or myocardial tissue.The results obtained from studies on the effect of hypoxia on isolated coronary artery tone are not consistent and range from dilation or decreases in isometric force (3,8,12,34) to constriction or increases in isometric force (9,18,22,26,30) or no effect at all (7). Efforts to understand oxygen-sensitive mechanisms by means of studying isolated cells complicated things even more.…”

“…The results obtained from studies on the effect of hypoxia on isolated coronary artery tone are not consistent and range from dilation or decreases in isometric force (3,8,12,34) to constriction or increases in isometric force (9,18,22,26,30) or no effect at all (7). Efforts to understand oxygen-sensitive mechanisms by means of studying isolated cells complicated things even more.…”