Endothelium-dependent regulatory mechanisms in human coronary bypass grafts: possible clinical implications

The internal mammary artery and saphenous vein are used as grafts in patients undergoing coronary bypass surgery. Different biological properties of arterial and venous grafts might contribute to the better graft function, lower patient mortality and higher patency rate of the mammary artery. We investigated the role of endothelium-derived relaxing factor (EDRF), which is a vasodilator and inhibitor of platelet function, in arterial and venous grafts. In mammary arteries, acetylcholine, thrombin, adenosine diphosphate, histamine and the calcium ionophore A23187 evoked endothelium-dependent relaxations blocked by hemoglobin or methylene blue, but not by cyclooxygenase inhibitors delineating EDRF as the mediator; in vascular smooth muscle cells, this was associated with a rise in intracellular cyclic GMP. Exogenous nitric oxide evoked potent endothelium-independent relaxations. In the saphenous vein, endothelium-dependent relaxations to all agonists, except the calcium ionophore, were weak, indicating heterogenous endothelium-dependent vascular reactivity as compared to the artery. The mammary and saphenous vein exhibited an enhanced sensitivity to nitric oxide. The greater release of EDRF in the internal mammary artery, particularly in response to platelet derived products, could contribute to the higher patency rate of arterial as compared to venous grafts and give new insights into mechanisms involved in graft function and vascular occlusion in man.