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.

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.

Abstract 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. (hSV CABG (CABG discussed antiischaemic anti ischaemic

Abstract 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.

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.

Abstract The saphenous vein is the most common conduit used in coronary artery bypass grafting (CABG) yet its failure rate is higher compared to arterial grafts. An improvement in saphenous vein graft performance is therefore a major priority in CABG. No-touch harvesting of the saphenous vein is one of the few interventions that has shown improved patency rates, comparable to that of the left internal thoracic artery. After more than two decades of no-touch research, this technique is now recognized as a Class IIa recommendation in the 2018 European Society of Cardiology and the European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization. In this review, we describe the structural alterations that occur in conventional versus no-touch saphenous vein grafts and how these changes affect graft patency. In addition, we discuss various strategies aimed at repairing saphenous vein grafts prepared at conventional CABG.

Abstract 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.

ResumoIntrodução:A febre reumática representa um sério problema de saúde pública em países em desenvolvimento, com milhares de novos casos a cada ano. Ela é uma doença autoimune que ocorre em resposta à infecção por estreptococos do grupo A.Objetivo:O objetivo deste estudo foi avaliar a expressão proteica e imunohistoquímica para a endotelina-1 e 3 (ET-1 e ET-3) e seus receptores (ETA e ETB) em valvas mitrais reumáticas.Métodos:Imunohistoquímica foi utilizada para identificar receptores de ET1/ET3 e ETA/ETB em valvas mitrais reumáticas e controles. A análise quantitativa da expressão imunohistoquímica para receptores de ET1/ET3 e ETA/ETB foi também efetuada. Adicionalmente, foi feita análise do western blot para mensurar níveis de proteínas em extratos tissulares.Resultados:A expressão imunohistoquímica de ET-1 e de seu receptor predominou em valvas estenóticas, estando associada com regiões fibróticas, áreas inflamatórias e neovascularização. A análise quantitativa mostrou que a área média com expressão positiva para ET-1 foi de 18,21±14,96%. Para o ETA e o ETB, as áreas médias expressas foram, respectivamente, 15,06±13,13% e 9,20±11,09%. ET-3 não teve uma expressão significante. A correlação entre a expressão dos dois receptores de endotelina foi fortemente positiva (R=0,74, P=0,02); mas a correlação entre ET-1 e o seu receptor foi negativa tanto para ETA (R=-0,37, P=0,25) como para ETB (R=-0,14, P=0,39). Estes dados foram confirmados pela análise do western blot.Conclusão:A forte correlação entre ET-1 e seus receptores sugere que ambos têm papel importante na fisiopatologia da estenose mitral reumática, podendo potencialmente atuar como biomarcadores desta doença.

AbstractIntroduction:Rheumatic Fever represents a serious public health problem in developing countries, with thousands of new cases each year. It is an autoimmune disease, which occurs in response to infection by streptococcus A.Objective:The aim of this study was to evaluate the immunolabeling and protein expression for endothelin-1 and 3 (ET-1, ET-3) and its receptors (ETA, ETB) in rheumatic mitral valves.Methods:Immunohistochemistry was used to identify ET-1/ET-3 and ETA/ETB receptors in rheumatic and control mitral valves. Quantitative analysis of immunostaining for ET-1/ET-3 and ETA/ETB receptors was performed. In addition, western blot analysis was carried out to assess protein levels in tissue samples.Results:ET-1 and ETA receptor immunostaining predominated in stenotic valves, mainly associated with fibrotic regions, inflammatory areas and neovascularization. Quantitative analysis showed that the average area with positive expression of ET-1 was 18.21±14.96%. For ETA and ETB, the mean expressed areas were respectively 15.06±13.13% and 9.20±11.09%. ET-3 did not have a significant expression. The correlation between the expression of both endothelin receptors were strongly positive (R=0.74, P=0.02), but the correlation between ET-1 and its receptor were negative for both ETA (R=-0.37, P=0.25), and ETB (R=-0.14, P=0.39). This data was supported by western blot analysis.Conclusion:The strong correlation between ET-1 and its receptors suggests that both play a role in the pathophysiology of rheumatic mitral valve stenosis and may potentially act as biomarkers of this disease.

FUNDAMENTO: Otimização da veia safena na revascularização miocárdica. OBJETIVO: Apresentar a técnica no-touch de preparo da veia safena. Essa técnica consiste na retirada da veia safena do seu leito, com um pedículo de tecido adiposo, protegendo-a contra espasmos, sendo desnecessário distendê-la. MÉTODOS: Estudo prospectivo e randomizado, incluindo 156 pacientes submetidos a cirurgia de revascularização miocárdica. Comparação da técnica no-touch com duas outras técnicas: convencional e intermediária. Procedeu-se à avaliação da morfologia endotelial, utilizando a microscopia. A perviabilidade das pontes foi determinada com exame angiográfico num período médio de 18 meses após a operação. A enzima óxido nítrico sintetase endotelial (eNOS) foi identificada por meio do estudo imunohistoquímico. RESULTADOS: A avaliação morfológica mostrou integridade endotelial de 97% nas veias do grupo no-touch; enquanto quase metade da superfície endotelial das veias tratadas pelas outras técnicas exibiu ausência de células endoteliais. A angiografia revelou perviabilidade de 95,4% para as pontes do grupo no-touch, 88,9 e 86,2% para as pontes do grupo convencional e intermediária, respectivamente. O estudo imunohistoquímico revelou a presença da eNOS nas três camadas que compõem a parede da veia no grupo no-touch e redução dessa enzima no grupo convencional. CONCLUSÃO: A integridade endotelial e a atividade da eNOS foram melhor preservadas com o uso da técnica no-touch. A proteção mecânica fornecida pelo tecido gorduroso circundante à veia e a atividade vasodilatadora e bloqueadora da agregação plaquetária causada pelo óxido nítrico podem ser responsáveis pela proteção da veia contra o espasmo, como também por sua alta perviabilidade imediata.

BACKGROUND: Optimization of the saphenous vein for myocardial revascularization. OBJECTIVE: To present the no-touch technique of the saphenous vein preparation. This technique consists of harvesting the vein with a pedicle of surrounding tissue, which protects the vein from spasms, obviating the need for distension. METHODS: A prospective, randomized study with 156 patients who underwent artery bypass grafting was performed comparing three saphenous vein harvesting techniques: conventional, intermediate, and no-touch. A morphological study of the endothelium was carried out using scanning microscopy. An angiographic assessment of the vein graft patency was performed at a mean follow-up time of 18 months. Also, an immunohistochemical assessment was carried out to identify the endothelial enzyme nitric oxide synthase (eNOS) in the vein wall RESULTS: The preservation of the endothelial cell integrity was greater in the no-touch technique than in the other procedures. At angiographic follow-up, the patency for the no-touch group was 95.4%, 88.9% for the grafts of the conventional technique group, and 86.2% for the grafts performed in the intermediate technique group. The immunohistochemical assessment revealed eNOS in all three layers of the vein wall in the no-touch group and reduction of this enzyme in the conventional group. CONCLUSION: The endothelial integrity and eNOS activity were better preserved when using the no-touch technique for vein graft harvesting. The mechanical protection provided by the cushion of surrounding tissue in the no-touch group, the vasorelaxation and thromboresistant activities of nitric oxide may be responsible for the reduction of vasospasms and improved patency rate.

OBJETIVO: O objetivo deste trabalho é apresentar uma nova técnica "no touch" de preparo da veia safena e sua importância clínica. Esta nova técnica consiste na retirada da veia safena do seu leito, juntamente com um pedículo de tecido adiposo, protegendo a veia contra espasmos e, conseqüentemente, da necessidade de distendê-la durante a operação. MÉTODO: O estudo foi realizado em dois tempos: 1) Inicialmente, foi realizado um estudo prospectivo e randomizado, envolvendo 156 pacientes que foram submetidos à operação de revascularização miocárdica. Neste estudo nós comparamos a técnica "no touch" (NT) com duas outras: a convencional (C) e a intermediária (I). Foi feita uma avaliação detalhada da morfologia endotelial, utilizando a microscopia eletrônica, enquanto que a perviabilidade das pontes foi determinada com um exame angiográfico executado num período médio de 18 meses após a operação. 2) Finalmente, a enzima óxido nítrico síntase (NOS) foi identificada com ajuda do estudo imunohistoquímico e também pela localização auto-radiográfica de (3H)-L- Nitro-Arginina (NOARG). RESULTADOS: A avaliação morfológica mostrou integridade endotelial de 97% nas veias que foram tratadas pela técnica NT; enquanto quase metade da superfície endotelial das veias tratadas pelas outras duas técnicas exibiu ausência de células endoteliais. O exame angiográfico revelou perviabilidade de 95,4% para as pontes do grupo NT, 88,9% para as pontes do grupo (C) e 86,2% para as pontes do grupo (I). O estudo imunohistoquímico revelou a presença de NOS nas três camadas que compõem a parede da veia quando, as mesmas, foram tratadas pela técnica NT. Por outro lado, foi observada uma elevada redução desta enzima nas veias que foram tratadas pela técnica (C). A análise auto-radiográfica confirmou os resultados imunohistoquímicos. CONCLUSÃO: A integridade endotelial e a atividade da enzima óxido nítrico síntase foram melhor mantidas com o uso da técnica NT no preparo da veia safena. A atividade vasodilatadora e bloqueadora da agregação plaquetária causada pelo óxido nítrico (NO) pode ser a responsável pela proteção da veia contra o espasmo, como também pela alta perviabilidade imediata da mesma. Além disso, as propriedades mecânicas providas pelo tecido gorduroso em volta da veia, contribuíram para o melhor resultado desta nova técnica.

BACKGROUND: The technique of harvesting the saphenous vein (SV) for coronary artery bypass grafting (CABG) influences the fate of vein grafts. A new "no touch" (NT) technique of SV preparation was developed where the vein is harvested with a pedicle of surrounding tissue, which protects the vein from spasms therefore obviating the need for distension. METHOD: A prospective randomized study in 156 patients who underwent CABG was performed comparing three SV harvesting techniques. The techniques were conventional (c) (adventitial stripping of the vein, manual distention and storing in saline solution); Intermediate (I) (after adventitial stripping, the vein was left in situ, covered with a papaverine-soaked compress, and stored in heparinized blood); and "no touch" (SV dissected with its surrounding tissue was left in situ, covered with a saline-soaked compress and stored in heparinized blood). A morphological study of the endothelium was preformed using scanning electronic microscopy and an angiographic assessment of the vein graft patency was performed at 18 months mean follow-up time. Also an immunohistochemistry assessment was performed to identify the enzyme, nitric oxide synthase (NOS) in the vein wall. RESULTS: The preservation of the endothelial cell integrity was greater with the "no touch" technique than with the other procedures. At angiographic follow up, the patency for NT was 95.4%, 88.9% for grafts in group C and 86.2% for grafts in group I. The immunohistochemistry assessment revealed NOS in all three layers of the vein wall that was prepared by the "no touch" technique. However, a great reduction of this enzyme in veins treated by the conventional technique was observed. CONCLUSION: The endothelial integrity and NOS activity were better preserved when using the "no touch" technique for vein graft harvesting. The vasorelaxation and thrombo-resistant activities of nitric oxide (NO) may be responsible for the reduced of vasospasms and improved patency rate. Furthermore, the mechanical properties provided by the cushion of surrounding tissue in graft harvested by NT technique may contribute to the observed high patency rate.