An Obligatory Role of Perivascular Adipose Tissue in Improved Saphenous Vein Graft Patency in Coronary Artery Bypass Grafting.

The gold standard graft for coronary artery bypass grafting (CABG) is the internal thoracic artery (ITA), and the second recommendation is the radial artery. However, complete revascularization with arterial grafts alone is often difficult, and the saphenous vein (SV) is the most commonly used autologous graft for CABG, because it is easier to use without restriction for the length of the graft. On the other hand, the patency of SV grafts (SVGs) is poor compared with that of arterial grafts. The SVG is conventionally harvested as a distended conduit with surrounding tissue removed, a procedure that may cause vascular damage. A no-touch technique of SVG harvesting has been reported to result in improved long-term patency in CABG comparable to that when using the ITA for grafting. Possible reasons for the excellent long-term patency of no-touch SVGs are the physical support provided by preserved surrounding perivascular adipose tissue, preservation of the vascular wall structure including the vasa vasorum, and production of adipocyte-derived factors. In this review, we discuss recent strategies aimed at improving the performance of SVGs, including no-touch harvesting, minimally invasive harvesting and mechanical support using external stents.

No-Touch Saphenous Vein - Vascular Damage and the London Connection.

In this review, I summarise the circumstances leading to the collaboration between London and Örebro on the basic research performed to study potential mechanisms underlying the improved patency of saphenous veins harvested by the no-touch technique. Histological studies reveal various forms of vascular damage to saphenous vein grafts harvested in conventional coronary artery bypass grafting (CABG) whereas no-touch grafts retain a normal architecture. The perivascular fat that remains intact on no-touch saphenous vein grafts seems to play a particularly important role as the "protector" of all layers of the graft. In addition, the perivascular fat is a source of adipose cell-derived factors that may contribute to the success of the no-touch technique. While a number of trials have compared no-touch with conventional grafts following CABG, these have generally been limited to short follow-up periods, low patient numbers, and inadequate histological data. When handling no-touch saphenous vein at harvesting, there is no direct contact of the vein by surgical instruments, spasm does not occur, and high-pressure intraluminal distension is not required. While damage to both endothelial and vascular smooth muscle cells are evident at the microscopic and ultrastructural level in conventional saphenous vein grafts, their structure in no-touch grafts is preserved. Also, in no-touch veins, the vasa vasorum remains intact and transmural blood supply is maintained. This microvascular network is disrupted during conventional harvesting, a situation likely to stimulate processes involved in graft occlusion. The use of excess graft material for histology is to be encouraged for the assessment of vascular damage and even surgeon competence. If you don't look, you don't find.

Towards Endoscopic No-Touch Saphenous Vein Graft Harvesting in Coronary Bypass Surgery.

The saphenous vein is the most used conduit for coronary artery bypass surgery. However, the patency rate of this graft is inferior to the internal thoracic artery patency rate, which is the gold standard. Using the conventional technique, the saphenous vein is harvested via a large open incision and excised in such a way that causes both vascular damage and wound healing complications. Consequently, vein graft patency and surgical site infection may be compromised. Graft patency is markedly improved when the saphenous vein is harvested atraumatically with minimal damage and with surrounding cushion of perivascular fat intact. However, despite the improved graft performance, wound healing complications and infection remain a problem. Although wound healing complication is reduced when using endoscopic vein harvesting, there may be a negative impact on graft performance. This is due to vascular damage associated with application of forces to the vein that are usually avoided in open vein harvesting, including traction, adventitial stripping, and venous compression. There is evidence to suggest that improved patency of endoscopically harvested saphenous veins is associated with the surgeon's experience of the technique. Recently, endoscopic methods of harvesting have been described where the saphenous vein is removed intact and with minimal vascular damage caused. In addition, wound healing complications, infection, and scarring are reduced. While the effect of these techniques on vein graft patency have yet to be reported, the ability to obtain a superior graft with reduced wound complications will be of great benefit to patients undergoing coronary revascularization procedures.

Depot- and diabetes-specific differences in norepinephrine-mediated adipose tissue angiogenesis, vascular tone, collagen deposition and morphology in obesity.

AIMS: Norepinephrine (NE) is a known regulator of adipose tissue (AT) metabolism, angiogenesis, vasoconstriction and fibrosis. This may be through autocrine/paracrine effects on local resistance vessel function and morphology. The aims of this study were to investigate, in human subcutaneous and omental adipose tissue (SAT and OAT): NE synthesis, angiogenesis, NE-mediated arteriolar vasoconstriction, the induction of collagen gene expression and its deposition in non-diabetic versus diabetic obese subjects. MATERIALS AND METHODS: SAT and OAT from obese patients were used to investigate tissue NE content, tyrosine hydroxylase (TH) density, angiogenesis including capillary density, angiogenic capacity and angiogenic gene expression, NE-mediated arteriolar vasoconstriction and collagen deposition. KEY FINDINGS: In the non-diabetic group, NE concentration, TH immunoreactivity, angiogenesis and maximal vasoconstriction were significantly higher in OAT compared to SAT (p < 0.05). However, arterioles from OAT showed lower NE sensitivity compared to SAT (10-8 M to 10-7.5 M, p < 0.05). A depot-specific difference in collagen deposition was also observed, being greater in OAT than SAT. In the diabetic group, no significant depot-specific differences were seen in NE synthesis, angiogenesis, vasoconstriction or collagen deposition. SAT arterioles showed significantly lower sensitivity to NE (10-8 M to 10-7.5 M, p < 0.05) compared to the non-diabetic group. SIGNIFICANCE: SAT depot in non-diabetic obese patients exhibited relatively low NE synthesis, angiogenesis, tissue fibrosis and high vasoreactivity, due to preserved NE sensitivity. The local NE synthesis in OAT and diabetes desensitizes NE-induced vasoconstriction, and may also explain the greater tissue angiogenesis and fibrosis in these depots.

No-Touch Saphenous Vein - Vascular Damage and the London Connection

ABSTRACT In this review, I summarise the circumstances leading to the collaboration between London and Örebro on the basic research performed to study potential mechanisms underlying the improved patency of saphenous veins harvested by the no-touch technique. Histological studies reveal various forms of vascular damage to saphenous vein grafts harvested in conventional coronary artery bypass grafting (CABG) whereas no-touch grafts retain a normal architecture. The perivascular fat that remains intact on no-touch saphenous vein grafts seems to play a particularly important role as the "protector" of all layers of the graft. In addition, the perivascular fat is a source of adipose cell-derived factors that may contribute to the success of the no-touch technique. While a number of trials have compared no-touch with conventional grafts following CABG, these have generally been limited to short follow-up periods, low patient numbers, and inadequate histological data. When handling no-touch saphenous vein at harvesting, there is no direct contact of the vein by surgical instruments, spasm does not occur, and high-pressure intraluminal distension is not required. While damage to both endothelial and vascular smooth muscle cells are evident at the microscopic and ultrastructural level in conventional saphenous vein grafts, their structure in no-touch grafts is preserved. Also, in no-touch veins, the vasa vasorum remains intact and transmural blood supply is maintained. This microvascular network is disrupted during conventional harvesting, a situation likely to stimulate processes involved in graft occlusion. The use of excess graft material for histology is to be encouraged for the assessment of vascular damage and even surgeon competence. If you don't look, you don't find.

Towards Endoscopic No-Touch Saphenous Vein Graft Harvesting in Coronary Bypass Surgery

ABSTRACT The saphenous vein is the most used conduit for coronary artery bypass surgery. However, the patency rate of this graft is inferior to the internal thoracic artery patency rate, which is the gold standard. Using the conventional technique, the saphenous vein is harvested via a large open incision and excised in such a way that causes both vascular damage and wound healing complications. Consequently, vein graft patency and surgical site infection may be compromised. Graft patency is markedly improved when the saphenous vein is harvested atraumatically with minimal damage and with surrounding cushion of perivascular fat intact. However, despite the improved graft performance, wound healing complications and infection remain a problem. Although wound healing complication is reduced when using endoscopic vein harvesting, there may be a negative impact on graft performance. This is due to vascular damage associated with application of forces to the vein that are usually avoided in open vein harvesting, including traction, adventitial stripping, and venous compression. There is evidence to suggest that improved patency of endoscopically harvested saphenous veins is associated with the surgeon's experience of the technique. Recently, endoscopic methods of harvesting have been described where the saphenous vein is removed intact and with minimal vascular damage caused. In addition, wound healing complications, infection, and scarring are reduced. While the effect of these techniques on vein graft patency have yet to be reported, the ability to obtain a superior graft with reduced wound complications will be of great benefit to patients undergoing coronary revascularization procedures.

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.

Saphenous veins in coronary artery bypass grafting need external support.

The saphenous vein is the most commonly used conduit for coronary artery bypass grafting. Arterial grafts are harvested with the outer pedicle intact whereas saphenous veins are harvested with the pedicle removed in the conventional graft harvesting technique. This conventional procedure causes considerable vascular damage. One strategy to improve vein graft patency has been to provide external support. Ongoing studies show that fitting a metal external support improves conventionally harvested saphenous vein graft patency. On the other hand, the no-touch technique of harvesting the saphenous vein provides an improved graft with long-term patency comparable to that of the internal mammary artery. This improvement is suggested to be due to preservation of vessel structures. Interestingly, many of the mechanisms proposed to be associated with the beneficial actions of an artificial external support on saphenous vein graft patency are similar to those underlying the beneficial effect of no-touch saphenous vein grafts where the intact outer layer acts as a natural support. Additional actions of external supports have been advocated, including promotion of angiogenesis, increased production of vascular-protective factors, and protection of endothelial cells. Using no-touch harvesting, normal vascular architecture is maintained, tissue and cell damage is minimized, and factors beneficial for graft patency are preserved. In this review, the significance of external support of saphenous vein grafts in coronary artery bypass grafting is discussed.

COVID-19 - Endothelial Axis and Coronary Artery Bypass Graft Patency: a Target for Therapeutic Intervention?

It has been reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces endothelial inflammation, therefore facilitating the progression of endothelial and vascular dysfunction in coronavirus disease 2019 (COVID-19) patients. Coronary artery bypass grafting (CABG) involves mainly the use of the saphenous vein (SV) and internal mammary artery as graft material in the stenosed coronary arteries. Unfortunately, graft patency of the SV is low due to endothelial dysfunction and inflammation. We propose that SARS-CoV-2 might cause vascular inflammation, endothelial dysfunction, and thrombosis in coronary artery bypass graft vessels by binding angiotensin-converting enzyme 2 receptor. Therefore, in this Special Article, we consider the potential influence of COVID-19 on the patency rates of coronary artery bypass graft vessels, mainly with reference to the SV. Moreover, we discuss the technique of SV graft harvesting and the therapeutic potential of focusing on endothelial dysfunction, vascular inflammation, and thrombosis for protecting coronary artery bypass grafts in COVID-19 infected CABG patients.

Covid-19 - endothelial axis and coronary artery bypass graft patency: a target for therapeutic intervention?

Abstract It has been reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces endothelial inflammation, therefore facilitating the progression of endothelial and vascular dysfunction in coronavirus disease 2019 (COVID-19) patients. Coronary artery bypass grafting (CABG) involves mainly the use of the saphenous vein (SV) and internal mammary artery as graft material in the stenosed coronary arteries. Unfortunately, graft patency of the SV is low due to endothelial dysfunction and inflammation. We propose that SARS-CoV-2 might cause vascular inflammation, endothelial dysfunction, and thrombosis in coronary artery bypass graft vessels by binding angiotensin-converting enzyme 2 receptor. Therefore, in this Special Article, we consider the potential influence of COVID-19 on the patency rates of coronary artery bypass graft vessels, mainly with reference to the SV. Moreover, we discuss the technique of SV graft harvesting and the therapeutic potential of focusing on endothelial dysfunction, vascular inflammation, and thrombosis for protecting coronary artery bypass grafts in COVID-19 infected CABG patients.

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.

Regional Distribution of Nitric Oxide Synthase in Human Anorectal Tissue: A Pilot Study on the Potential Role for Nitric Oxide in Haemorrhoids.

OBJECTIVE: To study the distribution of nitric oxide synthase (NOS) isoforms and protein levels in human haemorrhoids and rectal tissue. METHODS: Protein expression of NOS1, NOS2 and NOS3 was compared between haemorrhoids (n=14) and normal rectal submucosa (n=6) using Western blot analysis. The localisation of all NOS isoforms to specific structures was determined by immunohistochemistry. RESULTS: Western blot analysis showed median (interquartile range) protein levels of all NOS isoforms were 1.5-2.4 times higher in haemorrhoids than rectal tissue; 121.4 (55.2-165.5) vs 50.0 (25.5-73.7) for NOS1 (p=0.020), 32.2 (23.8-140.6) vs 14.8 (9.6-34.0) for NOS2 (p=0.109), and 80.1 (62.0-139.5) vs 54.3 (48.7 -61.7) for NOS3 (p=0.015). Immunohistochemistry revealed a different distribution and location of all NOS isoforms in vascular and non-vascular structure of haemorrhoids and rectal tissues. The number of haemorrhoid specimens showing positive immunoreactivity of NOS in the vascular endothelium was significantly higher than that in rectal tissue for NOS1 (11/14 (79%) vs 1/6 (17%); p=0.018) and NOS3 (8/14 (57%) vs 0/6 (0%); p=0.042), but not for NOS2 (6/14 (43%) vs 4/6 (67%); p=0.63). CONCLUSION: Haemorrhoids have significantly higher protein levels of NOS1 and NOS3 than rectal tissue. The vascular endothelium of haemorrhoids also has significantly higher positive immunoreactivity of NOS1 and NOS3 than rectal tissue suggesting that blood vessels in haemorrhoids are exposed to higher NO concentrations than those of rectal tissue. Since haemorrhoids exhibit marked vascular dilatation and present with bleeding or swelling, a reduction in NOS - by applying NOS inhibitors - may potentially improve the symptoms of haemorrhoids.