Vasomotion and endothelial function of arterial and venous coronary bypass grafts: in vivo evaluationt
(1998)
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- Coronary artery bypass surgery is now a widely used therapeutic measure for symptomatic coronary artery disease. Many studies have been performed since Vineberg, in 1946, described three experimental approaches to grafting the internal thoracic artery directly into heart muscle. The first aorto-coronary bypass graft was performed only on 1964 by Garret, with a saphenous vein segment anastomosed to the anterior descending artery. In 1967, a Russian surgeon, Kolessov reported six patients with grafting of the mammary artery to the left anterior descending artery, but most centres during the next decade were using only saphenous vein graft. <BR> However, several teams (Grondin, 1984; Loop, 1986) showed a higher patency rate in mammary graft than in saphenous venous graft, and this was associated with an improved survival and a decreased morbidity for these patients. Zeff et al, in 1988 demonstrated for the first time in a prospective randomized study an increase in survival in patients with mammary grafts anastomosed to the left anterior descending artery, in comparison to patients with venous grafts anastomosed to the same coronary bed. <BR> A lot of work has been done during the past 10 years to expand the use of arterial grafts to the coronary circulation. However, it has become clear that all conduits are not the same and our knowledge of the physiology of venous and arterial grafts has increased markedly. In parallel with the enhanced use of arterial conduits for myocardial revascularization, an accelerated interest in the biology of the vascular endothelium occurred. Initially, the vascular endothelium was regarded as a relative passive “barrier” between the blood and the arterial media. Today, vascular endothelium is considered as one of the most regulatory organ in human biology, playing a critical role not only on the patency of the grafts but also in their functional performance. It is well known now that the endothelium plays a role as an activator and inactivator of circulating and locally produced hormones, and serves as an antothrombotic barrier as well as a modulator of vascular tone and growth (Lüscher, 1994). <BR> One of the primary functions of the endothelium is thus to maintain vascular tone (relaxation and contraction). This is accomplished through production of several relaxing and contracting factors that influence underlying smooth muscle. <BR> - Chief among vasodilators is endothelium-derived relaxing factor (EDRF), first identified by Furchgott and Zawadski (1980) and known to be nitric oxide (NO). Endothelial cells synthetize NO from L-arginine via activity of the enzyme NO synthase. In the normal endothelium, there is a continuous release of low levels of NO than maintains vascular tone locally, to keep the vasculature in a constant state of dilation under basal conditions. Endogenous substances that can stimulate release of NO include acetylcholine, bradykinin, histamine, thrombin, platelet products, adenosine diphosphate and triphosphate and substance P. Physical factors such as shear stress and changes in oxygen tension also stimulate release of NO. Shear stress appears to be a major physiologic stimulus for NO release from normal endothelium. NO has a number of physiologic roles not only in the regulation of vascular tone and in the autoregulation of blood flow, but also in the control of myocardial contractility, endothelial integrity and permeability, vascular cell proliferation, endothelial-leukocyte interactions and antithrombotic properties. Response to NO is mediated through stimulation of soluble guanylate clyclase and formation of cyclic guanosine monophosphate (cGMP). <BR> - Prostacyclin (PGI2) is produced in response to shear stress and to other mediators of NO production. PGI2 is a platelet-inhibitory metabolite of arachidonic acid which has a synergistic action with EDRF, inducing not only a vasorelaxation via an increase in cyclic AMP (cAMP) but also an inhibition of platelet aggregation and smooth muscle cells proliferation. <BR> - Other endogenous vasodilators include endothelium-derived hyperpolarizing factor (EDHF), which causes vasodilation by hyperpolarizing vascular smooth muscle through stimulation of efflux through potassium ion channels, and bradykinin, which is a nonapeptide produce also by the endothelium in response to flow. Bradykinin has direct vasodilator effects and acts indirectly by promoting the release of NO and EDHF. Bradykinin has other effects on the vasculature, including inhibition of platelet aggregation and adhesion (in synergy with NO and PGI2), of tissue remodelling, of smooth cell proliferation and of macrophages adherence to the vessel wall. As a potent stimulator of tissue plasminogen activator (t-PA) secretion from the endothelium, bradykinin has a beneficial antothrombotic effect. Local endothelial angiotensin-converting enzyme (ACE) continuously breaks down bradykinin and thus ACE inhibitors, which are clinically largely used, potentiate the actions of bradykinin, resulting in vasodilation and proliferation. <BR> - The endothelium also modulates vascular tone by regulating the expression of endothelial-derived vasoconstrictors, such as thromboxane A2 (TXA2) endothelin and angiotensin II, which counterbalance locally produced vasodilators. <BR> - Endothelin is a 21-amino-acid peptide identified by Yanagisawa et al (1988) and is the most potent vasoconstrictor known. It is produced by endothelial cells in response to stimulation by a variety of substances, including thrombin, transforming growth factor-β (TGF-β), interleukin-1, epinephrine, angiotensin II, arginine vasopressin, calcium ionophores and phorbol ester but also by ischemia or hypoxemia. Endothelin production is regulated by three inhibitory mechanisms: c-GMP-dependent inhibition, which can be activated by NO (negative feedback mechanism), cyclic adenosine monophosphate (c-AMP) – dependent inhibition and an inhibitory factor produced by vascular smooth muscle cells. At the level of vessels, endothelin induces a vasoconstriction via receptors ETA, located on smooth muscular cells (and less importantly via ETB2 receptors). Inversely, endothelin can induce a vasodilation via ETB1 receptors, located on endothelial cells, via a stimulation of NO and PGI2. <BR> Angiotensin II, another peptide, can be considered also as an endothelium-derived contracting factor since ACE is found on the surface of endothelial cells. In addition to its direct constrictor effect on vascular smooth muscle cells, via AT1 receptors AII has an indirect vasoconstrictor effect by stimulating the release of endothelin. Behind this control of vascular tone, endothelial cells produce or process many growth factors, including fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), endothelin, angiotensin II, Interleukin I, … Endothelial cells also produce growth inhibitors, including heparin, heparin sulfates and transforming growth factor β (TGF-β). Although the endothelial-dependent mechanisms regulating cell proliferation and anti-proliferation are not well understood, NO (via a mechanism that is C-GMP-dependent) is known to have several antiproliferative effects on the vasculature. <BR> Finally, the endothelium maintains a non adhesive luminal surface and regulates anticoagulant, fibrinolytic and antithrombotic mechanisms. The normal endothelium maintains a delicate balance between factors that regulate thrombosis and those that regulate fibrinolysis. Once again, NO, in synergy with PGI2, has an important role in the antithrombotic properties of the endothelium. NO and PGI2 are equally potent inhibitors of platelet aggregation, but their effects are mediated by different mechanisms. <BR> Therefore, the endothelium constitutes a key element in a vascular conduit, and will serve in this work as an index to evaluate and to compare several coronary bypass conduits used in our institution. <BR> Our study was developed in three steps. First, we will review, the mechanisms explaining the superiority of the internal mammary artery to saphenous veins for coronary bypass surgery and the possible similarities between the inferior epigastric artery and the gastroepiploic artery, the two main challengers of the internal mammary artery. Second, we will try to analyze in vivo the vasomotion and the endothelial function of several grafts. We will compare these aspects between early after surgery (just prior hospital discharge) and late after surgery, in chronic grafts. Besides the comparison between mammary and venous grafts, we will perform the same approach in grafts performed with the inferior epigastric artery (a free aortocoronary graft) and with the gastroepiploic artery (a pedicled graft), trying to assess in vivo their endothelial function. Finally, we will try to clarify the mechanism by which arterial and venous coronary bypass conduits adapt their flow to an increase in myocardial demand.
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Gurné, O. (1998). Vasomotion and endothelial function of arterial and venous coronary bypass grafts: in vivo evaluationt. https://hdl.handle.net/2078.5/111486