Nerve-perivascular fat communication as a potential influence on the performance of blood vessels used as coronary artery bypass grafts.

Perivascular fat, the cushion of adipose tissue surrounding blood vessels, possesses dilator, anti-contractile and constrictor actions. The majority of these effects have been demonstrated in vitro and may depend on the vessel and/or the experimental method or species used. In general, the relaxant effect of perivascular adipose tissue is local and may be either endothelium-dependent or endothelium-independent. However, nerve stimulation studies show that, in general, perivascular adipose tissue (PVAT) has an anti-contractile vascular effect likely to involve an action of the autonomic vascular nerves. Apart from a direct effect of perivascular fat-derived factors on bypass conduits, an interaction with a number of neurotransmitters and other agents may play an important role in graft performance. Although the vascular effects of PVAT are now well-established there is a lack of information regarding the role and/or involvement of peripheral nerves including autonomic nerves. For example, are perivascular adipocytes innervated and does PVAT affect neuronal control of vessels used as grafts? To date there is a paucity of electrophysiological studies into nerve-perivascular fat control. This review provides an overview of the vascular actions of PVAT, focussing on its potential relevance on blood vessels used as bypass grafts. In particular, the anatomical relationship between the perivascular nerves and fat are considered and the role of the perivascular-nerve/fat axis in the performance of bypass grafts is also discussed

Saphenous Vein Vasa Vasorum as a Potential Target for Perivascular Fat-Derived Factors

Perivascular adipose tissue (PVAT) is a source of factors affecting vasomotor tone with the potential to play a role in the performance of saphenous vein (SV) bypass grafts. As these factors have been described as having constrictor or relaxant effects, they may be considered either beneficial or detrimental. The close proximity of PVAT to the adventitia provides an environment whereby adipose tissue-derived factors may affect the vasa vasorum, a microvascular network providing the vessel wall with oxygen and nutrients. Since medial ischaemia promotes aspects of graft occlusion the involvement of the PVAT/vasa vasorum axis in vein graft patency should be considered

Endothelin-1, endothelin receptor antagonists, and vein graft occlusion in coronary artery bypass surgery: 20 years on and still no journey from bench to bedside

The saphenous vein is the most commonly used bypass graft in patients with coronary artery disease. During routine coronary artery bypass, grafting the vascular damage inflicted on the vein is likely to stimulate the release of endothelin-1, a potent endothelium-derived vasoconstrictor that also possesses cell proliferation and inflammatory properties, conditions associated with vein graft failure. In both in vitro and in vivo studies, endothelin receptor antagonists reduce neointimal thickening. The mechanisms underlying these observations are multifactorial and include an effect on cell proliferation and cell/tissue damage. Much of the data supporting the beneficial action of endothelin-1 receptor antagonism at reducing intimal thickening and occlusion in experimental vein grafts were published over 20 years ago. The theme of the recent ET-16 conference in Kobe was “Visiting Old and Learning New”. This short review article provides an overview of studies showing the potential of endothelin receptor antagonists to offer an adjuvant therapeutic approach for reducing saphenous vein graft failure and poses the question why this important area of research has not been translated from bench to bedside given the potential benefit for coronary artery bypass patients

A Brief Comment on Vasa Vasorum of Human Saphenous Vein: relevance for Coronary Artery Bypass Surgery

The importance of the vasa vasorum and blood supply to the wall of human saphenous vein (hSV) used for coronary artery bypass grafting (CABG) is briefly discussed. This is in the context of the possible physical link of the vasa vasorum connecting with the lumen of hSV and the anti-ischaemic impact of this microvessel network in the hSV used for CABG

Why Use the Radial Artery? The Saphenous Vein is the Second Graft of Choice for CABG in Brazil

The saphenous vein (SV) is the most commonly used conduit for coronary artery bypass surgery (CABG) and the second conduit of choice in Brazil and many other countries. The radial artery (RA) is suggested, by some, to be superior to SV grafts, although its use in the USA declined over a 10 year period. The patency of SV grafts (SVG) is improved when the vein is harvested with minimal trauma using the no-touch (NT) technique. This improved performance is due to the preservation of the outer pedicle surrounding the SV and reduction in vascular damage that occurs when using conventional techniques (CT) of harvesting. While the patency of NT SVGs has been shown superior to the RA at 36 months in one study, data from the RADIAL trial suggests the RA to be the superior conduit. When additional data using NT SVG is included in this trial the difference in risk of graft occlusion between the RA and SV grafts dissipates with there no longer being a significant difference in patency between conduits. The importance of preserving SV structure and the impact of NT harvesting on conduit choice for CABG patients are discussed in this short review

What is the impact of preserving the endothelium on saphenous vein graft performance? Comments on the 'NO' touch harvesting technique.

Saphenous veins used for coronary artery bypass surgery are subjected to considerable vascular trauma when harvested by conventional methods. This vascular damage is responsible, at least in part, for the inferior patency of the saphenous vein when compared with the internal thoracic artery. The performance of saphenous vein grafts is improved when this conduit is harvested atraumatically using the no-touch technique. There is growing evidence that the success of the no-touch technique is due to the preservation of a number of vascular structures including the endothelium, vasa vasorum and perivascular fat. There is conflicting evidence regarding the degree of endothelial damage to the endothelium of conventional versus no-touch saphenous vein grafts. In general, it has been shown that this single layer of cells lining the lumen exhibits considerable damage associated with a combination of vascular trauma and high pressure intraluminal distension. Increased platelet aggregation and thrombus formation at the exposed subendothelial membrane is due to a local reduction of endothelium-derived factors including nitric oxide. In addition, damage to the vasa vasorum of conventionally-harvested veins will reduce transmural blood flow, a condition shown to promote neointimal hyperplasia and atheroma formation. By stripping off the perivascular fat during conventional harvesting, mechanical support of the graft is reduced and the source of adipocyte-derived factors potentially beneficial for graft patency removed. While most agree that endothelial damage to the saphenous vein affects graft patency, the contribution of other tissue-derived factors affected by vascular damage at harvesting need to be considered

Vasa vasorum inside out/outside in communication: a potential role in the patency of saphenous vein coronary artery bypass grafts

The saphenous vein (SV) is the most commonly used conduit for revascularization in patients undergoing coronary artery bypass surgery (CABG). The patency rate of this vessel is inferior to the internal thoracic artery (ITA). In the majority of CABG procedures the ITA is removed with its outer pedicle intact whereas the (human) SV (hSV) is harvested with pedicle removed. The vasa vasorum, a microvessel network providing the adventitia and media with oxygen and nutrients, is more pronounced and penetrates deeper towards the lumen in veins than in arteries. When prepared in conventional CABG the vascular trauma caused when removing the hSV pedicle damages the vasa vasorum, a situation affecting transmural flow potentially impacting on graft performance. In patients, where the hSV is harvested with pedicle intact, the vasa vasorum is preserved and transmural blood flow restored at graft insertion and completion of CABG. By maintaining blood supply to the hSV wall, apart from oxygen and nutrients, the vasa vasorum may also transport factors potentially beneficial to graft performance. Studies, using either corrosion casts or India ink, have shown the course of vasa vasorum in animal SV as well as in hSV. In addition, there is some evidence that vasa vasorum of hSV terminate in the vessel lumen based on ex vivo perfusion, histological and ultrastructural studies. This review describes the preparation of the hSV as a bypass conduit in CABG and its performance compared with the ITA as well as how and why its patency might be improved by harvesting with minimal trauma in a way that preserves an intact vasa vasorum

Divalent metal inhibition of non-haem iron uptake across the rat duodenal brush border membrane

Duodenal Fe2+ uptake is essential to body Fe2+ homeostasis, but the interaction of metals with the uptake process remains unclear. The present study compared the effects of four essential trace metals (Mn2+, Zn2+, Co2+ and Ni2+) with two toxic metals (Pb2+ and Cd2+) on Fe2+ uptake across the brush border membrane of villus-attached duodenal enterocytes. Everted rat duodenum was exposed to buffer containing 0.2 mm-Fe-59(2+)-ascorbate with or without the competing metal (2 mm) and the tissue was then processed for autoradiography allowing Fe2+ uptake to be determined at specific crypt-villus regions. The quantification method ensured that uptake by cells, rather than Fe2+ binding to the tissue surface, was measured. Fe2+ uptake was significantly inhibited by Cd2+ in upper villus enterocytes only and Pb2+ was without effect on Fe2+ uptake. The inhibition by Cd2+ was not due to general cell damage as judged by the release of lactate dehydrogenase from tissue into incubation fluid. Essential divalent trace metals reduced uptake significantly along the whole length of the crypt-villus axis. Cd2+ uptake, measured separately, took place at all regions of the villus-crypt axis, highest uptake being into crypt enterocytes. The very different uptake profiles for Cd2+ and Fe2+ suggests that the divalent metal transporter 1 is not the principal transporter of Cd2+. The addition of Fe2+ to incubation buffer inhibited Cd2+ uptake by both crypt and villus enterocytes. The possibility that the inhibitory actions of Fe2+ and Cd2+ on the uptakes of Cd2+ and Fe2+ respectively can be explained by a non-competitive action or the involvement of an additional metal transporter is discussed