Sidney George Shaw, DPhil (1948-2017).

On March 4, 2017 at the age of 68, Sidney George Shaw (Sid) unexpectedly died from complications following surgery, only four years after retiring from the University of Bern. Trained in biochemistry at Oxford University, Sid had quickly moved into molecular pharmacology and became a key investigator in the field of enzyme biochemistry, vasoactive peptide research, and receptor signaling. Sid spent half his life in Switzerland, after moving to the University of Bern in 1984. This article, written by his friends and colleagues who knew him and worked with him during different stages of his career, summarizes his life, his passions, and his achievements in biomedical research. It also includes personal memories relating to a dear friend and outstanding scientist whose intellectual curiosity, humility, and honesty will remain an example to us all.

Role of PVAT in coronary atherosclerosis and vein graft patency: friend or foe?

Perivascular adipose tissue (PVAT) releases numerous factors and adipokines with paracrine effects on both vascular structure and function. These effects are variable as they depend on regional differences in PVAT among blood vessels and vary with changes in adiposity. There is considerable evidence demonstrating an association between coronary PVAT and the development and progression of coronary artery disease, which is associated with inflammation, oxidative stress, angiogenesis, vascular remodelling and blood clotting. However, PVAT also has a protective role in vascular grafts, especially the no-touch saphenous vein, in patients undergoing coronary artery bypass. This beneficial influence of PVAT involves factors such as adipocyte-derived relaxing factor, nitric oxide (NO), leptin, adiponectin, prostanoids, hydrogen sulphide and neurotransmitters, as well as mechanical protection. This article aims to highlight and compare the dual role of PVAT in the development and progression of coronary atherosclerosis, as well as in increased graft patency. Different deleterious and protective mechanisms of PVAT are also discussed and the inside-outside signalling paradigm of atherosclerosis development re-evaluated. The bidirectional communication between the arterial and venous wall and their surrounding PVAT, where signals originating from the vascular wall or lumen can affect PVAT phenotype, has been shown to be very complex. Moreover, signals from PVAT also influence the structure and function of the vascular wall in a paracrine manner. LINKED ARTICLES: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.

Dual effects of α2 -adrenoceptors in modulating myogenic tone in sheep isolated internal anal sphincter.

BACKGROUND: The role of α-adrenoceptors in promoting continence through modulation of sphincter tone has focused primarily on the effects of α1 -adrenoceptors. We have used three clinically available agents, which are selective for α2 -adrenoceptors, to investigate their role in contractile and neurogenic responses on the internal anal sphincter (IAS). METHODS: IAS strips, which had spontaneously generated tone, were used to investigate the contractile effect of lofexidine, brimonidine, and dexmedetomidine on muscle tone in the presence or absence of subtype selective antagonists. The effect of brimonidine on the magnitude and time course of neurogenic responses generated by electrical field stimulation (EFS) was also examined. The affinity of test compounds at α1 - and α2 -adrenoceptors was established by competition binding with [3H]-prazosin and [3H]-RX821002. KEY RESULTS: All agonists caused concentration-dependent contraction of the IAS and lofexidine demonstrated an enantiomeric difference in potency with a 10-fold difference between the (-) and (+) isomers. Responses to lofexidine and dexmedetomidine were inhibited in the presence of the α1 -adrenoceptor selective antagonist prazosin, but not in the presence of RX811059 (α2 -adrenoceptor selective antagonist); brimonidine responses were inhibited by RX811059 and, to a lesser extent, by prazosin. Brimonidine affected both magnitude and duration of neurogenic responses, which was reversed in the presence of RX811059. CONCLUSIONS & INFERENCES: We conclude that α2 -adrenoceptors can mediate contraction of IAS, although this effect is most evident with efficacious imidazoline agonists rather than the most selective ligand. In addition, this receptor subtype can directly inhibit noradrenergic contractile responses to EFS and, indirectly, enhance nitrergic relaxatory responses.

Investigation of the distribution and function of alpha-adrenoceptors in the sheep isolated internal anal sphincter.

BACKGROUND AND PURPOSE: We have investigated the distribution of alpha-adrenoceptors in sheep internal anal sphincter (IAS), as a model for the human tissue, and evaluated various imidazoline derivatives for potential treatment of faecal incontinence. EXPERIMENTAL APPROACH: Saturation and competition binding with (3)H-prazosin and (3)H-RX821002 were used to confirm the presence and density of alpha-adrenoceptors in sheep IAS, and the affinity of imidazoline compounds at these receptors. A combination of in vitro receptor autoradiography and immunohistochemistry was used to investigate the regional distribution of binding sites. Contractile activity of imidazoline-based compounds on sheep IAS was assessed by isometric tension recording. KEY RESULTS: Saturation binding confirmed the presence of both alpha(1)- and alpha(2)-adrenoceptors, and subsequent characterization with sub-type-selective agents, identified them as alpha(1A)- and alpha(2D)-adrenoceptor sub-types. Autoradiographic studies with (3)H-prazosin showed a positive association of alpha(1)-adrenoceptors with immunohistochemically identified smooth muscle fibres. Anti-alpha(1)-adrenoceptor immunohistochemistry revealed similar distributions of the receptor in sheep and human IAS. The imidazoline compounds caused concentration-dependent contractions of the anal sphincter, but the maximum responses were less than those elicited by l-erythro-methoxamine, a standard non-imidazoline alpha(1)-adrenoceptor agonist. Prazosin (selective alpha(1)-adrenoceptor antagonist) significantly reduced the magnitude of contraction to l-erythro-methoxamine at the highest concentration used. Both prazosin and RX811059 (a selective alpha(2)-adrenoceptor antagonist) reduced the potency (pEC(50)) of clonidine. CONCLUSIONS AND IMPLICATIONS: This study shows that both alpha(1)- and alpha(2)-adrenoceptors are expressed in the sheep IAS, and contribute (perhaps synergistically) to contractions elicited by various imidazoline derivatives. These agents may prove useful in the treatment of faecal incontinence.

Endothelin-1 and vein graft occlusion in patients undergoing bypass surgery.

The saphenous vein is the most commonly used graft for revascularization procedures in patients with coronary artery disease and critical limb ischaemia. However, the patency rate of this vessel is poor, with a high proportion of patients requiring further surgery. Early graft occlusion is caused by vasoconstriction or thrombus formation, with later stages of graft failure being due to neointimal formation or atherosclerosis. Apart from its potent constrictor action, endothelin-1 is also a potent proliferative and proinflammatory peptide that is implicated in a number of vascular diseases. The surgical trauma caused during preparation of the saphenous vein as a bypass graft stimulates the release of a number of factors affecting vascular reactivity and structure, including endothelin-1. Endothelin-1 not only constricts animal and human isolated saphenous vein segments but also causes vascular smooth muscle proliferation and neointimal thickening in vitro, actions that are mediated via endothelin (A and B) receptors. Experimentally, the effects of subtype-selective and dual receptor antagonists have been shown to inhibit endothelin-1-mediated constriction and cell proliferation of the saphenous vein. In this review, data supporting a role of endothelin-1 in vein graft occlusion are presented, and the therapeutic potential of endothelin receptor antagonists in improving graft performance is discussed.

Nitric oxide synthase in critically ischaemic muscle and alterations in isoform expression during revascularization surgery.

BACKGROUND: Dysfunction of the nitric oxide pathway is implicated in peripheral arterial disease. Nitric oxide synthase (NOS) isoforms and NOS activity were studied in muscle from patients with critical leg ischaemia (CLI). Alterations in NOS during revascularization surgery were also assessed. METHODS: Muscle biopsies were taken from patients with CLI undergoing amputation and also from patients undergoing femorodistal bypass at the start of surgery, after arterial clamping and following reperfusion. The presence of NOS within muscle sections was confirmed using reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. NOS isoform distribution was studied by immunohistochemistry. NOS mRNA and protein levels were measured using real-time reverse transcriptase-polymerase chain reaction and western blotting. NOS activity was assessed with the citrulline assay. RESULTS: All three NOS isoforms were found in muscle, associated with muscle fibres and microvessels. NOS I and III protein expression was increased in CLI (P = 0.041). During revascularization, further ischaemia and reperfusion led to a rise in NOS III protein levels (P = 0.008). NOS activity was unchanged. CONCLUSION: Alterations in NOS I and III occurred in muscle from patients with CLI and further changes occurred during bypass surgery.

Altered endothelin-1 levels in acute lower limb ischemia and reperfusion.

Tourniquet-induced ischemia is often used in orthopedic and reconstructive procedures. This is associated with muscle damage and dysfunction, which limits tourniquet application time. Endothelin-1 (ET-1) is a potent vasoconstrictor, which has been implicated in ischemic conditions and ischemia-reperfusion injury. This study aimed to investigate the role of ET-1 in human skeletal muscle subjected to tourniquet-induced acute ischemia and reperfusion. Thirteen patients undergoing total knee replacement were studied. Plasma and muscle ET-1 concentrations were measured at the start of surgery, after an hour of acute ischemia, and 15 minutes following reperfusion. ET-1 receptor binding was also studied by use of autoradiography, and ET-1 mRNA expression investigated by use of real-time polymerase chain reaction (RT-PCR). Tissue ET-1 increased following the period of acute ischemia and persisted during reperfusion. ET-1 was associated with microvessels and macrophages in the muscle. No changes in circulating ET-1 levels, ET-1 mRNA expression, or ET-1 receptor binding were found. It is concluded that the ET-1 pathway is involved in acute ischemia and reperfusion and it may contribute to the muscle injury that occurs during surgical procedures.

Human saphenous vein and coronary bypass surgery: ultrastructural aspects of conventional and "no-touch" vein graft preparations.

Coronary artery bypass graft surgery (CABG) is routinely used to restore blood flow to diseased cardiac muscle due to coronary artery disease. The patency of conventional grafts decreases with time, which is due to thrombosis and formation of neointima. A primary cause of graft failure is the mechanical damage inflicted to the graft during harvesting, including removal of surrounding tissue accompanied by high pressure saline distension to overcome vasospasm (both causing considerable mechanical trauma). The aim of this study was to compare the ultrastructural features of human saphenous vein (SV) grafts harvested conventionally and grafts prepared using an atraumatic 'no-touch' harvesting technique introduced by Souza (1996). The results of this study showed a better preservation of the lumenal endothelium and medial vascular smooth muscle (SM) in 'no-touch' versus conventional grafts. A 'fast' (within 30 min) response of SM cells to conventional harvesting was noted where features of both SM cell division and apoptosis were observed. It is concluded that the 'preserved' nature of the 'no-touch' aortocoronary SV grafts renders them less susceptible to thrombotic and atherosclerotic factors than grafts harvested conventionally. These features are suggested to contribute to the improved early patency rate described using the no-touch technique of SV harvesting.

Down-regulation of nitric oxide synthase in the diabetic rabbit kidney: potential relevance to the early pathogenesis of diabetic nephropathy.

OBJECTIVES: Nephropathy is a well-recognised complication of diabetes mellitus (DM). The aim of this study was to investigate the effect of DM on the density and distribution of nitric oxide (NO) synthase (NOS) in the rabbit kidney. Quantification of the NOS radioligand on slide-mounted sections was compared with the nitroblue tetrazolium reaction, where the intensity of the reaction varies with the nicotinamide adenine dinucleotide diaphorase (NADPH-d) activity of NOS. MATERIALS AND METHODS: DM was induced with alloxan in six New Zealand White (NZW) rabbits. Plasma creatinine, urea and electrolytes were monitored at monthly intervals. The kidneys were removed following 6 months of DM. Transverse serial sections were cut and low-resolution autoradiography was performed using a radioligand for NOS ([(3)H]-NOARG). Histochemical localisation of NADPH-d activity was also performed. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from six age-matched control rabbits. RESULTS: There was a significant (p < 0.01) rise in plasma creatinine levels in the diabetic rabbits, although the mean values remained within the reference range. There was a significant (p < 0.0001) down-regulation of NOS binding sites in both the cortex and medulla of the DM kidney when compared with the controls. A similar decrease in NADPH-d activity was seen in the diabetic renal cortex and medulla. In addition, NADPH-d activity also appeared to be reduced in the diabetic glomeruli when compared with controls. CONCLUSIONS: NOS binding sites and NADPH-d activity are significantly decreased in the DM renal cortex and medulla. These changes are associated with a mild deterioration in renal function and may be an early event that could subsequently play a role in the progression of DM nephropathy. Manipulating the NO pathway during the early stages of DM nephropathy may be beneficial.

Evidence for the involvement of endothelin-1 but not urotensin-II in chronic lower limb ischaemia in man.

BACKGROUND: endogenous vasoconstrictor peptides may play a role in the pathophysiology of critical limb ischaemia (CLI). This study investigated endothelin-1 (ET-1) and urotensin-II (U-II) mRNA expression, peptide distribution and ET receptor subtype binding in chronically ischaemic muscle. METHODS: open muscle biopsies were taken from patients undergoing amputations for CLI and from patients undergoing coronary artery bypass surgery (controls). ET-1 and U-II mRNA expression in muscle biopsies was studied using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). ET-1 and U-II immunohistochemistry was performed on muscle sections and ET receptor binding studied using in vitro autoradiography. RESULTS: ET-1 mRNA expression was significantly increased in CLI compared to controls (p<0.05) whilst no significant change in U-II expression occurred. ET-1 immunoreactivity was also increased in CLI with no difference in U-II immunostaining observed. ET(B) receptor binding was significantly increased in CLI (median 4, range 1-8 vs 2, range 1-3, dpm x 10(3)/mm(2), p=0.01, Mann-Whitney test) whilst ET(A) receptor binding was not significantly raised. Binding was associated with microvessels and macrophages. CONCLUSIONS: in CLI, the ET-1 pathway is upregulated but U-II is unaffected. ET-1 may vasoconstrict microvessels and mediate inflammation in chronically ischaemic muscle. ET-1 binding to ET(B) receptors in particular may play an important role in the pathophysiology of CLI underscoring the therapeutic potential of ET(B) receptor antagonists in the management of CLI.

Detection of glucagon receptor mRNA in the rat proximal tubule: potential role for glucagon in the control of renal glucose transport.

Glucagon is known to affect glomerular filtration rate and renal tubular solute and fluid transport, although it is only thought to act directly on the thick ascending limb (TAL) and collecting duct (CD). Indeed, previous studies have detected glucagon-sensitive adenylate cyclase exclusively in these nephron segments, suggesting the presence of glucagon receptors. In the present study, we have demonstrated for the first time that glucagon receptor mRNA is expressed in the rat proximal tubule, as well as in the TAL and CD. By autoradiography, we have also shown that specific binding of glucagon occurs in both the renal cortex and medulla. In addition, using proximal tubule brush-border membrane (BBM) vesicles for studies of glucose transport, we have established that glucagon stimulates glucose uptake via a facilitative GLUT-mediated transport process (by 58%; P < 0.005), whereas cAMP stimulates only the sodium glucose-linked transporter ('SGLT')-mediated glucose uptake (by 53%; P < 0.05). Taken together, these findings suggest that glucagon could have a role in controlling proximal tubular transport function, including glucose reabsorption, but unlike in the TAL and CD, the proximal tubule glucagon receptor might not be coupled primarily to adenylate cyclase.

Endothelin-1 and nitric oxide in the pathogenesis of urinary tract disorders secondary to bladder outlet obstruction.

Bladder outlet obstruction (BOO) is a common disorder that is associated with urinary tract symptoms. Nitric oxide (NO), synthesized by NO synthase (NOS) is a potent vasodilator that is present throughout the urinary tract and the corpus cavernosum. Endothelin-1 (ET-1) conversely is a potent vasoconstrictor peptide that is similarly distributed throughout the urinary tract. ET-1 and NO as well as possessing opposing actions regulate each other's synthesis. The disruption of the balance between ET-1 and NO is associated with various vascular pathologies. However, their potential roles in the pathogenesis of urinary tract disorders, secondary to BOO, is not well established. New Zealand White rabbits with BOO are considered to be a suitable model of the human condition. Hence, using this model, we systematically investigated the potential roles of ET-1 and NO in the pathogenesis of the various urological disorders associated with BOO. In this review we discuss the results of our studies, which support the concept that an imbalance between ET-1 and NO may be associated with the pathogenesis of urinary tract disorders secondary to BOO. We also discuss the potential clinical implications of this association. This review is based on the Bard Silver Medal Lecture given (by MAK) at the 2002 British Association of Urological Surgeons (BAUS) annual meeting.

Enhanced relaxation of diabetic rabbit cavernosal smooth muscle in response to nitric oxide: potential relevance to erectile dysfunction.

New Zealand white rabbit cavernosal smooth muscle strips (n=6) were mounted in organ baths. Relaxations to nitric oxide (10(-7)-10(-4) mol/l) were measured and the same procedure was repeated on strips from rabbits 6 months after alloxan-induced diabetes (n=6). Transverse cavernosal sections were obtained from the same penises. Low and high resolution autoradiographs were prepared using [(3)H]-L-N(G)-nitroarginine (an index of nitric oxide binding sites) and analysed densitometrically. Histochemical analysis was performed on adjacent sections using NADPH diaphorase (an index of nitric oxide synthase activity). Nitric oxide relaxed control rabbit cavernosal smooth muscle strips in a concentration-dependent manner. Diabetic rabbit cavernosal smooth muscle strips were significantly (P<0.03) more sensitive to nitric oxide (mean IC(50)=3.9 x 10(-6) mol/l). Nitric oxide synthase binding sites were localised to the cavernosal endothelium and smooth muscle. Nitric oxide synthase activity was increased in 6 month diabetic cavernosal smooth muscle. These findings suggest impairments in the L-arginine-nitric oxide pathway may play a role in the pathophysiology of diabetic erectile dysfunction.

Potential role of endothelin 1 in ischaemia-induced angiogenesis in critical leg ischaemia.

BACKGROUND: Ischaemia-induced angiogenesis occurs in critical leg ischaemia (CLI) and endothelin (ET) 1 may be involved in this process. The aim of this study was to quantify microvessels and study ET receptor expression and distribution in critically ischaemic leg muscle. METHODS: Leg muscle biopsies were taken from 12 patients with CLI and 12 patients with no leg ischaemia. Microvessels were identified immunohistochemically on muscle sections, and the number of immunopositive cells was quantified. ETA and ETB receptor messenger RNA (mRNA) expression was studied using real-time quantitative reverse transcriptase-polymerase chain reaction, and receptor binding was localized and assessed by in vitro autoradiography. RESULTS: The number of microvessels in CLI muscle biopsies was 2.6 times higher than that in controls (P < 0.01). ETB receptor mRNA expression and binding were significantly increased in CLI tissue (P < 0.05), while ETA receptor levels were not significantly raised. High-resolution autoradiography showed that ET receptor binding was associated with microvessels. CONCLUSION: Angiogenesis occurs in CLI and raised ETB receptors within the muscle were associated with microvessels, suggesting that ET-1 may mediate angiogenesis via these receptors in critically ischaemic muscle.

Recent strategies to reduce vein graft occlusion: a need to limit the effect of vascular damage.

Despite early identification and aggressive modification of atherosclerotic risk factors, many patients still require surgical revascularisation for established atherosclerotic vascular disease. However, bypass surgery is hampered by a high incidence of vein graft failure. New strategies are being introduced to improve these results, with early data suggesting that improved patency rates are possible. These vary from the use of adjuvant pharmacological agents and local gene transfer strategies to the modification of vein harvesting techniques in order to reduce vascular damage to all layers of the graft. Advances in vascular biology have resulted in new insights into the role of the endothelium and adventitia in vein graft remodelling. Although recent pharmacological adjuvant therapy and molecular techniques have been described that may be used to reduce the incidence of vein graft occlusion a more desirable approach for improved graft patency rates may be achieved simply by using atraumatic surgical techniques aimed at minimising vascular damage during vessel harvesting and subsequent anastamoses during bypass surgery.

Endothelin receptors in the aetiology and pathophysiology of varicose veins.

INTRODUCTION: varicose veins are tortuous and poorly contractile. Their aetiology remains unclear. Neovascularisation has been suggested as a possible explanation. Endothelins are mitogenic, promoting proliferation and migration of endothelial cells via endothelin-B receptors. We hypothesise that endothelial cells and endothelin receptor density and distribution may play a role in the development of varicosis. METHODS: saphenous vein segments from nine patients with varicose veins were compared to six controls. Slide-mounted sections were incubated in radioactive labelled endothelin-1 and receptor subtype-selective ligands and binding sites assessed using autoradiography. Endothelin-1 and endothelial cells were identified by immunohistochemistry and CD31-positive staining cells counted. RESULTS: radioactive labelled endothelin-1 and endothelin-B receptor binding was reduced in varicose compared to control veins (p=0.04). Endothelin-A receptor binding was diffuse, with no difference in density in both groups (p=0.58). Endothelin-B receptor binding was diffuse with superimposed clusters. Although the density of medial endothelin-B receptor binding was reduced in the varicose group, more clusters were identified in this group compared to controls (p=0.005). CD-31 staining identified these clusters as endothelial cells. CONCLUSION: the reduced endothelin-1 binding and endothelin-B receptor density may be partially responsible for the reduced vasocontractility in varicose veins. We speculate that the increase in endothelin-B receptor binding CD31-positive endothelial cells in varicose veins may potentially stimulate mitogenesis and migration, leading to new vessel formation.

Does external stenting reduce porcine vein-graft occlusion via an action on vascular nerves?

BACKGROUND: Neural reorganization occurs in porcine vein grafts and placement of an external stent reduces graft occlusion. AIM OF THE STUDY: To determine the effect of external stenting on the innervation of porcine vein grafts. METHODS: Saphenous vein into carotid artery grafting (with and without external stents) was performed in 16 pigs. After one and six months, grafts were removed, nerves were counted, and neointima was assessed. RESULTS: In vein graft compared to ungrafted vein, there was a significant (p < 0.05) decrease in medial perivascular nerves, but a dramatic increase in paravascular nerves in the adventitia (p < 0.05). In stented vein grafts there was also a reduction of perivascular nerves and the paravascular nerve proliferation observed in vein grafts at one month was inhibited (p < 0.05). Neointima formation and the appearance of large paravascular nerve bundles in the adventitia of vein grafts were abolished by external stenting. CONCLUSIONS: Neural reorganization plays a role in vein-graft failure, possibly through the local release of mitogens; the prevention of this reorganization contributes to the inhibitory effect of the external stent on neointima formation.

Preserved endothelial integrity and nitric oxide synthase in saphenous vein grafts harvested by a 'no-touch' technique.

BACKGROUND: The saphenous vein is the most commonly used conduit for coronary artery bypass surgery, but 1-year occlusion rates as high as 30 per cent have been reported. In conventional surgery, considerable damage to the vein occurs during harvesting. The aim of this study was to compare endothelial integrity and nitric oxide synthase (NOS) in saphenous veins harvested by a novel 'no-touch' technique and veins harvested conventionally. METHODS: Immunohistochemistry was used to study endothelial integrity, and a combination of histochemistry and autoradiography was employed to identify NOS in human saphenous veins harvested by conventional and no-touch techniques. RESULTS: The endothelial lining of conventional grafts was reduced compared with that of no-touch grafts (52 versus 73 per cent; P = 0.04). This was associated with a concomitant reduction of NOS availability; NOS was also present in the adventitial vasa vasorum of no-touch vessels. CONCLUSION: Some of the sites with potential for nitric oxide release in vivo are removed during conventional saphenous vein harvesting. These sites were preserved after no-touch harvesting, suggesting the potential to improve coronary artery bypass graft patency.

High early patency of saphenous vein graft for coronary artery bypass harvested with surrounding tissue.

BACKGROUND: Surgical trauma to the saphenous vein, used as a conduit for coronary artery bypass grafting, affects their occlusion rate. This study evaluates the early patency of saphenous vein grafts harvested with a pedicle of surrounding tissue that protects the vein from spasm and trauma. METHODS: Fifty-two patients underwent coronary artery bypass grafting with saphenous veins harvested with surrounding tissue. Forty-five patients, who received a total of 124 vein grafts and 42 left internal mammary arteries, underwent angiographic follow-up at a mean of 18 months (9 to 24 months). RESULTS: Patency for saphenous vein grafts was 95.4% and for left internal mammary arteries, it was 93.3%. Twenty-nine of 30 (96.7%) vein grafts anastomosed to arteries 2.0 mm or more, 65 of 67 (97%) grafts to 1.5 mm, and 10 of 13 (77%) anastomosed to 1-mm arteries were patent. Nineteen of 22 (86.4%) vein grafts with flow rates 20 mL/min or less, 32 of 34 (94.1%) with flow between 20 and 40 mL/min, and 50 of 51 (98%) with flow more than 40 mL/min were patent. Other registered surgical and clinical factors did not contribute to vessel occlusion. CONCLUSIONS: Early patency rate of saphenous veins harvested with surrounding tissue is very high, even in saphenous vein grafts demonstrating low blood flow. Preservation of graft endothelium using our harvesting technique may be the explanation of this success.