Influence of oxygenation on endothelial modulation of coronary vasomotor function during hyperkalemic cardioplegia

Abstract

Background: The purpose of this study was to determine the influence of oxygenation of a hyperkalemic cardioplegic solution (K-CP) on endothelial modulation of vasomotor tone and to correlate these changes with the intracellular calcium concentration ([Ca ++] i) in microvascular smooth muscle. Methods: Rat coronary arterioles were studied in a pressurized, no-flow normothermic state. Simultaneous monitoring of luminal diameter and [Ca ++] i (fura-2) was performed with use of microscopic image analysis. Vessels were subjected to 60 minutes of oxygenated or hypoxic K-CP (K + = 25.0 mmol/L) and were then reperfused with oxygenated Krebs–physiologic saline solution for 60 minutes. Results: In oxygenated K-CP, the K-CP–induced contraction and [Ca ++] i accumulation were significantly increased in endothelium-denuded (ED) vessels compared with endothelium-intact vessels. The effect of ED in oxygenated K-CP was mimicked by administration of the nitric oxide synthase inhibitor N G-monomethyl- L -arginine. Conversely, in hypoxic K-CP the contraction was significantly attenuated in ED vessels compared with endothelium-intact vessels, although there was no significant difference in [Ca ++] i. Indomethacin did not affect the endothelium-dependent contraction during hypoxic K-CP. Conclusions: Endothelium-derived nitric oxide modulates the vascular tone during K-CP by regulating the vascular smooth muscle [Ca ++] i, whereas endothelium-derived contracting factor(s), which is not predominantly a product of cyclo-oxygenase, may play a prominent role under hypoxic K-CP by increasing vascular smooth muscle Ca ++ sensitivity. (Surgery 1999;126:264-71.)