The arteriovenous fistula and the history of a forgotten pioneer.

Objective: The radiocephalic arteriovenous fistula (AVF), first introduced by Dr Kenneth Charles Appell, allowed for the provision of hemodialysis for patients with chronic kidney disease (CKD) and remains a reliable method for vascular access today. The purpose of this study is to review the contributions that led to the development of the AVF. We describe the work of Dr Appell, whose procedure bypassed the need for repeated cannulation in achieving vascular access, transforming the management of patients with dialysis-dependent CKD. Methods: A literature search was conducted by searching "arteriovenous fistula," "history of surgery," "hemodialysis," "vascular access," "chronic kidney disease," "repeated cannulation," and "Kenneth Charles Appell" on PubMed, Embase, and Web of Science. Only articles written in English were considered. Results: Before the arteriovenous fistula, glass cannulae were used for vascular access, beginning with Abel's "vividiffusion" apparatus in animals and Haas's experimental dialysis on humans. The use of glass cannulae was continued by Kolff, who transitioned from venipuncture needles to glass cannulae. However, these attempts were complicated by thrombosis, excessive bleeding related to heparin use, and damage to vascular access sites from repeated cannulation. Arteriovenous shunts, using polytetrafluoroethylene tubing, were an improvement from previous attempts at vascular access, but were prone to local bleeding, shunt occlusion, phlebitis, cellulitis, and rarely lasted more than a few months. To address these challenges, Dr Appell created an upper extremity AVF, allowing for the provision of maintenance dialysis without externalized devices, repeated cannulation, and extensive anticoagulant administration. Despite Dr Appell's vision and pioneering contributions to vascular surgery, he has received little credit for his work. Conclusions: The enormous contribution by Dr Appell in the development of the AVF that transformed the modern management of patients with CKD is recognized in this review of the history of vascular access surgery for hemodialysis.

Evaluation of aortic tortuosity as a negative predictor of abdominal aortic aneurysm rupture.

OBJECTIVE: The maximal aortic diameter has been used as a key indication for whether to repair abdominal aortic aneurysms (AAAs). Aortic tortuosity has been proposed as another factor to consider. In the present study, we compared the degree of aortic tortuosity in ruptured AAAs with that of unruptured AAAs using computed tomography. METHODS: We performed a retrospective review of a prospectively maintained database of patients who had undergone AAA repair from December 2014 to December 2019. Patients with a ruptured aneurysm (rAAA) were matched with patients with a nonruptured AAA (nrAAA) with the same maximal aneurysm diameter and age. The degree of aortic tortuosity, defined as the maximum lateral deviation from the aortic centerline, was measured on preoperative coronal computed tomography scans. RESULTS: During a 5-year period, 572 AAA cases were identified. The aortic tortuosity of the 25 rAAA cases was compared with that of a matched control group of 31 nrAAAs, selected by the same mean maximum diameter of 8.4 cm and similar patient age. In the rAAA group, the mean age was 74.8 years (84% men). In the nrAAA group, the mean age was 76.3 years (88% men). The mean aortic tortuosity for the rAAA and nrAAA groups was 9.3 ± 7.9 mm and 18.0 ± 11.2 mm, respectively (P < .01). CONCLUSIONS: Greater aortic tortuosity was seen in the nrAAA cases compared with the rAAA cases at the same matched aneurysm size. Thus, aortic tortuosity might confer a reduced rupture risk. Further studies with larger cohorts are needed to verify this observation.

Survey of Canadian vascular surgeons and trainees finds work-related musculoskeletal pain and discomfort is common.

BACKGROUND: Occupational injuries and disability are a source of surgeon morbidity. The purpose of this study was to assess the physical toll of working in operating rooms by Canadian vascular surgeons. OBJECTIVE: To assess workplace musculoskeletal (MSK) complaints and challenges faced by Canadian vascular surgeons and trainees and their implications on surgical practice and occupational longevity. METHODS: An online survey was distributed to resident and surgeon members of the Canadian Society of Vascular Surgery. The survey collected data on demographics, operative volume, and work-related MSK symptoms. RESULTS: The survey was distributed to 188 surgeons and trainees. After three e-mailings, 109 surveys were returned (58% response rate). Of the responders, 87% were male, 51% were 45 years or older, and 56% had been in practice for 10 or more years. Workplace MSK symptoms were reported by 83% of the responders. The most common locations were the low back (78%), neck (74%), and shoulder (30%). Most responders (83%) believed that these symptoms were related to their operative environment. Almost half (48%) sought medical care. As a result of these MSK symptoms, 25% experience chronic pain with 8% reporting time off work as a consequence. Another 11% reported an impact on their operative performance with 14% considering early retirement. A lack of operating room system changes to prevent workplace injury and disability was noted by 85% of the responders although only 3% reported their disability to their department. CONCLUSIONS: Occupational MSK symptoms and disability are common among Canadian vascular surgeons. Further research is needed to create programs to improve surgeon morbidity.

Canadian experience with percutaneous endovascular aneurysm repair: short-term outcomes.

BACKGROUND: To decrease the morbidity associated with cut-downs during endovascular aneurysm repair, some authors have suggested the totally percutaneous endovascular repair (PEVAR). The goal of this report is to evaluate and describe our centre's experience with the total percutaneous endovascular aneurysm repair (PEVAR) for aortic abdominal aneurysm (AAA). METHODS: We performed a retrospective analysis of 15 consecutive patients with AAA, including 1 with right common iliac artery aneurysm. RESULTS: There were 12 men and 3 women with a mean age of 74 (standard deviation [SD] 2) years who underwent PEVAR with a Perclose ProGlide suture-mediated closure system between July 2007 and July 2008. All surgeries were elective. Forty percent of patients had a history of smoking, 73% were hypertensive, 33% were diabetic, 20% had chronic obstructive pulmonary disease and 40% had coronary artery disease. Fourteen patients had bilateral deployment for bifurcated devices (7 bifurcated Gore Excluder, 7 bifurcated Cook Zenith grafts), and 1 patient had unilateral deployment for a Cook Zenith device. The outer diameter of the sheaths used for puncture sites was on average 18.1-Fr (SD 0.6), with main bodies being 21.1-Fr (SD 0.3) and contralateral sides 15-Fr (SD 0.3). Procedural success was 93%, with 1 patient requiring a femoral artery cut-down because of failure of the Perclose device to deploy in the groin. Another patient had persistent venous bleeding in 1 puncture site that stopped with skin suturing. Endovascular aneurysm repair was 100% with no conversion to open surgery and no type-I endoleaks. The mean length of stay in hospital was 2.2 (SD 0.4) days. There were no long-term groin complications at 6 (SD 1) months' follow-up. CONCLUSION: To our knowledge, this is the first Canadian report of experience with PEVAR using the Perclose device. The technique is safe, reliable and allows discharge of patients soon after surgery.

Arterialization of a vein graft promotes cell cycle progression through Akt and p38 mitogen-activated protein kinase pathways: impact of the preparation procedure.

BACKGROUND: Vein arterialization following bypass surgery often leads to graft occlusion, but the underlying cellular mechanisms have been poorly studied. OBJECTIVES: Cell cycle progression and the activation of proliferation signalling were compared in arterialized grafts prepared either according to the conventional procedure or using pharmacological relaxation with the native vein. METHODS: Using the porcine carotid-jugular bilateral interposition graft model on one side, a segment of porcine jugular vein was prepared for grafting using the conventional procedure, with pressure distention at 300 mmHg; the segment grafted on the other side was treated with a combination of pharmacological vasodilators. Both veins were grafted into the carotid artery for two weeks. RESULTS: On the immunolabelling of proliferation cell nuclear antigen, a greater number of proliferating cells was found in the conventionally prepared grafts compared with pharmacologically prepared grafts. Cyclin D1 expression and phosphorylation of retinoblastoma increased after implantation, coinciding with nuclear accumulation of beta-catenin, activation of the Akt and mitogen-activated protein kinase cascades, and upregulated phosphatase and tensin homologue phosphorylation. Replacement of distention with pharmacological relaxation reduced the increase in cyclin D1 expression, phosphorylation of retinoblastoma, Akt-Thr(308), glycogen synthase kinase 3 beta and p38, but not extracellular signal-regulated kinases. This technique preserved the active phosphatase and tensin homologue, as well as the expression of cyclin-dependent kinase inhibitor p21(Cip1), while elevating the expression of p27(Kip1). CONCLUSIONS: It was concluded that two-week arterial implantation stimulates proliferation signalling and promotes the cell cycle in vein grafts. Replacement of the conventional preparation procedures with pharmacological vasorelaxation restricts the activation of proliferation and cell cycle progression, and can be beneficial for improving vein graft patency.

Acidosis augments myogenic constriction in rat coronary arteries.

The myogenic response is a process by which blood vessels autoregulate vascular smooth muscle tone in response to changes in transmural pressure. It is characterized by vessel contraction or dilation with increased or decreased pressure, respectively. We sought to identify whether acidosis impacts the myogenic response in rat coronary resistance arteries. Ventricular septal arteries were isolated from male Sprague-Dawley rats and mounted on a pressure myograph. The myogenic response was assessed by measuring the arterial diameter at pressures of 10-120 mm Hg. The fluorescence indicators 2',7'-bis-(carboxyethyl)-5(and-6)-carboxyfluorescein and Fura-2 were utilized to measure intracellular pH (pH(i)) and intracellular free calcium concentration ([Ca(2+)](i)), respectively. A decrease in the extracellular pH (pH(o)) from 7.4 to 6.9 produced a fall in pH(i) and an increase in the myogenic response. Under nominally HCO (3) (-) /CO(2)-free conditions at a constant pH(o), blockade of the sodium-hydrogen exchanger with HOE694 also resulted in a fall in pH(i) and a similar enhancement of myogenic activity. Concentration response curves were constructed to measure the potencies of the HOE694 effects: the EC(50) was 34 microM for the pH(i) change and 19 microM for vessel constriction. Apparent [Ca(2+)](i) remained unchanged during HOE694-induced intracellular acidification. Furthermore, in the presence of HCO (3) (-) , HOE694 did not markedly affect pH(i) and vascular tone remained unaltered. Our data demonstrate that acidosis augments myogenic constriction of rat coronary arteries. These effects are due to a fall in pH(i) consequent upon the reduction in pH(o) and may reflect an increased myofilament [Ca(2+)](i) sensitivity within vascular smooth muscle cells.

Pharmacologic relaxation of vein grafts is beneficial compared with pressure distention caused by upregulation of endothelial nitric oxide synthase and nitric oxide production.

OBJECTIVE: Pressure distention of veins during preparation for bypass surgery is believed to impair vascular integrity and reduce graft patency. We previously suggested a combination of pharmacologic vasodilatators as an alternative to distention. Vascular homeostasis is largely regulated by nitric oxide. We investigated the role of distention in comparison with pharmacologic vasorelaxation in the regulation of nitric oxide synthases, nitric oxide bioavailability, and vascular reactivity in vein grafts. METHODS: In a porcine model the internal jugular vein from either side received pressure distention or the combination of vasodilators (alpha-adrenergic antagonist, phenoxybenzamine, 10 micromol/L; Rho-kinase inhibitor, HA-1077 [fasudil], 50 mumol/L; calcium blocker, nicardipine, 1 micromol/L) and then was grafted into the carotid artery. Regulation of nitric oxide synthase, as well as nitrate and nitrite levels, were examined in vein grafts after 2 weeks of implantation. RESULTS: Distention of jugular veins resulted in reduction of vasoconstriction in response to depolarization and agonist stimulation. Arterial grafting doubled inducible nitric oxide synthase expression in both grafts but caused a pronounced upregulation of endothelial nitric oxide synthase protein (by 57.3% +/- 5%) only in drug-treated grafts, whereas in distended grafts the endothelial nitric oxide synthase level was decreased by 27.5% +/- 2.7%. The downregulated endothelial nitric oxide synthase level in the distended grafts was accompanied by a 45.2% +/- 3.1% reduction of phospho-endothelial nitric oxide synthase Ser1177 levels and by a significant reduction in nitric oxide synthase activity (12.1% +/- 1.2%) and nitrate production (48.9% +/- 5.6%) in comparison with that seen in drug-treated grafts. CONCLUSIONS: Pharmacologic preparation of the vein grafts results in upregulation of endothelial nitric oxide synthase and increased nitric oxide production in the vein grafts after arterial implantation. This might provide greater clinical benefit than conventional pressure-distention methods.

Reduced expression of vascular endothelial growth factor paralleled with the increased angiostatin expression resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in human type 2 diabetic arterial vasculature.

Impaired angiogenesis could contribute to the increased incidence of coronary and peripheral artery disease in diabetic patients. Angiogenesis is initiated by vascular endothelial growth factor (VEGF), a potent angiogenic cytokine, and suppressed by angiostatin, which is generated by matrix metalloproteinase (MMP)-2 and -9 through proteolytic cleavage of plasminogen. We hypothesized that MMP-2 and -9 were upregulated in the diabetic vasculature, resulting in increased angiostatin production and reduced blood vessel formation. In diabetic internal mammary artery samples (n=32) collected from patients undergoing coronary artery bypass grafting surgery, capillary density was only 30% of that in the nondiabetic vessels (n=32), whereas VEGF expression was reduced by 48%. Diabetes upregulated the expression and the gelatinolytic activity of MMP-2 and -9. Active MMP-2 and -9 were released from diabetic arteries, but not from nondiabetic vessels, during phenylephrine-induced vasoconstriction. Diabetes enhanced transcription and protein expression of tissue inhibitor of MMP (TIMP)-1 but had an opposite effect on TIMP-2. In diabetic vessels angiostatin was increased by 62% and was positively correlated with the activities of MMP-2 and -9 (r2=0.806 and 0.742, respectively). This report indicated a strong correlation between the upregulation of MMP-2 and MMP-9 and the increased angiostatin expression in the human diabetic arterial vasculature. The enhanced angiostatin production with a reduced VEGF formation may explain the pathogenesis of impaired angiogenesis in diabetes mellitus.

Pressure distention compared with pharmacologic relaxation in vein grafting upregulates matrix metalloproteinase-2 and -9.

OBJECTIVE: Autogenous vein bypasses are a common and effective method to treat occlusive disease. During surgical preparation, veins are routinely pressure distended to overcome vasospasm and twists. Distention, however, is believed to promote vascular remodeling and contribute to decreased graft patency. Pharmacologic vasorelaxation with a combination of effective vasodilators has been suggested as an alternative to pressure distention. The extracellular matrix (ECM)-degrading matrix metalloproteinases (MMPs) have been implicated in vascular remodeling and neointima formation. The purpose of the present study was to compare the effects of pressure distention with pharmacologic vasorelaxation on graft remodeling and regulation of MMP-2 and MMP-9 in porcine vein grafts. METHODS: Carotid artery bypass utilizing internal jugular veins was performed in eight female white pigs. Jugular veins were randomized to receive pressure distention (300 mm Hg for 2 minutes) or a combination of vasodilators (the alpha-adrenergic antagonist phenoxybenzamine, 10 micromol/L; the Rho-kinase inhibitor HA-1077 [fasudil], 50 micromol/L; and the calcium-channel blocker nicardipine, 1 micromol/L) for 30 minutes and then were grafted into the carotid arteries. Two weeks after surgery, vein graft samples were analyzed for vessel intimal and medial area, lumen diameter, and ECM composition. Molecular analysis using reverse transcription-polymerase chain reaction, Western immunoblotting, gelatin zymography, and reverse zymography were performed to study the expression and activation of MMP-2 and MMP-9, and tissue inhibitors of MMP (TIMP)-1 and TIMP-2. RESULTS: Pressure distention irreversibly overstretched the porcine jugular vein and increased MMP-2 and MMP-9 proteolytic activity by 40% and 77%, respectively. Two weeks of vein grafting in the carotid arterial bed induced vessel wall thickening, ECM modification, and neointima formation, which were more pronounced in the distended grafts (P < .05) and accompanied by an increase in MMP expression and activity. Distended grafts demonstrated higher percentages of active MMP-9 (17.8% +/- 1.0%) and higher activities of latent (35.5% +/- 3.3%) and active MMP-2 (69.6% +/- 8.8%) than the pharmacologically treated grafts. Protein expression of TIMP-1 and TIMP-2 was downregulated after arterial grafting, but the pharmacologically treated grafts expressed significantly more TIMP-1 protein (by 36.8% +/- 4.1%) than the distended ones. The activities of TIMPs were markedly decreased after grafting, contributing to the upregulated MMP activity. CONCLUSIONS: Pressure distention of vein grafts before implantation, compared with pharmacologic vasodilatation, stimulates neointima formation and augments MMP activities. Pharmacologic vasorelaxation may be clinically superior to distention in attenuating graft remodeling and possibly improving graft patency. CLINICAL RELEVANCE: Autogenous vein bypasses are a common and effective method to treat occlusive disease. This study demonstrated that pressure distention, a common preparatory procedure in bypass surgery, upregulates extracellular matrix-degrading matrix metalloproteinases, which predisposes vein grafts to extensive remodeling and contributes to neointima formation and graft occlusion. The topical application of a combination of vasodilators to the vein graft before implantation may be clinically superior to pressure distention in attenuating graft remodeling and may possibly improve graft patency and reduce secondary surgical interventions.

Nosocomial MRSA infection in vascular surgery patients: impact on patient outcome.

Although methicillin-resistant Staphylococcus aureus (MRSA) infection is a worldwide problem, data on its significance among vascular surgery patients remain scant and conflicting. This study was designed to evaluate the association between nosocomial MRSA infection and patient outcome following vascular surgery procedures. Outcomes among patients with MRSA infection were also compared to those infected with methicillin-sensitive Staphylococcus aureus (MSSA). All patients admitted to a tertiary care Vascular Surgery ward during the year 2002 were included in this retrospective review. In addition to information on demographic and comorbid conditions, data on surgical interventions, nosocomial infection incidence rates as defined by the Center for Disease Control guidelines, and MRSA screening results were collected. Primary outcome was in-hospital death. Secondary outcomes measures included length of hospital stay, readmissions, or repeat surgeries, and ICU admissions. Of a total of 408 subjects, 110 were documented with a nosocomial infection (27.0%). Of these, 16 patients (3.9%) were colonized with MRSA on screening at time of admission, 22 (5.4%) had acquired MRSA infection during hospitalization, and 15 (3.7%) had MSSA infection. Patients with MRSA, MSSA, and non-MRSA infection had similar baseline characteristics except for hypertension and tobacco use. Age and MRSA infection were significant risk factors for in-hospital deaths (OR 1.07, 95% CI 1.01-1.13, p = 0.01 and OR 7.44, 95% CI 1.63-33.9, p = 0.01, respectively). Adjusted for the effects of age, MRSA infection remained a significant independent risk factor associated with in-hospital deaths (OR 4.38, 95% CI 1.09-17.7, p = 0.04). After adjustment for baseline risk factors, MRSA infection was also independently associated with secondary outcome measures. Although risks of non-MRSA infections were also associated with adverse outcomes in the multivariate analyses, MRSA posed higher risks, as reflected by higher odds ratio in all instances. The 22 patients with documented MRSA infection had significantly longer hospital stays than those with MSSA infection (median 24 days vs 8 days, p = 0.02). However, no significant differences were noted between the 2 groups in terms of secondary outcome. These results show that MRSA infection is a significant risk factor for adverse clinical outcomes among patients undergoing vascular surgery procedures. Infection with MRSA results in a greater risk of these outcomes when compared with non-MRSA infection. However, despite concerns regarding the virulence of this strain of staphylococcus, patients infected with MRSA had no higher rates of morbidity or mortality except for increased length of hospital stay when compared to patients with MSSA.

Effect of moderate pressure distention on the human saphenous vein vasomotor function.

BACKGROUND: Manual pressure distension, which is commonly applied to the human saphenous vein graft for coronary artery bypass, is believed to have detrimental consequences for the graft patency. The vasomotor function of the vein after distention during surgical preparation for grafting and after distention in laboratory conditions at pressure of 50 to 600 mm Hg was studied. The effect of a combination of vasodilative agents to prevent vasospasm was also tested. METHODS: The contractile and dilatory responses of distended and undistended human saphenous veins and those after drug treatment were examined in organ baths under isometric conditions. RESULTS: Distention at the pressure range 100 to 300 mm Hg resulted in an increased contractile response of the saphenous vein to both alpha-adrenergic activation with 50 micromol/L phenylephrine (153.73% +/- 15.69%) and depolarization with 80 mmol/L K(+) (141.03% +/- 15.13%) in comparison with the undistended vein and did not impair the relaxation. In contrast manual distention during surgical preparation abolished the contractile response and impaired the relaxation. The application of a combination of vasodilative drugs (alpha-adrenergic antagonist phenoxybenzamine, 10 micromol/L, Rho-kinase inhibitor HA-1077, 50 micromol/L, and calcium blocker nicardipine, 1 micromol/L) eliminated the contractile response of the vein to phenylephrine and 80 mmol/L K(+). This effect was sustained more than 20 hours after the washout of the drugs. CONCLUSIONS: The distention of the human saphenous vein at moderate pressure combined with the application of the effective combination of vasodilative drugs before grafting into the arterial circulation could be a beneficial alternative to the current practice of uncontrolled pressure distension.

Multidetector CT angiography of the aortoiliac system and lower extremities: a prospective comparison with digital subtraction angiography.

OBJECTIVE: Our objective was to determine whether multidetector CT (MDCT) angiography is an accurate and reliable method of revealing atheroocclusive disease of the aortoiliac system and the lower extremities compared with digital subtraction angiography (DSA). SUBJECTS AND METHODS: Forty-one patients with ischemic legs underwent both MDCT angiography and DSA of the aortoiliac system and the legs. The arterial supply of the legs was divided into 35 segments. Three independent observers rated each segment according to the maximal degree of arterial stenosis. Consensus interpretation was used to calculate the sensitivity and specificity of MDCT angiography in showing arterial occlusions and stenoses of at least 75%. Intertechnique agreement was measured for each anatomic segment, and interobserver agreement was calculated for both techniques. Agreement was quantified using the kappa statistic. RESULTS: The sensitivity and specificity of MDCT angiography for depicting arterial occlusions and stenoses of at least 75% were 88.6% and 97.7%, and 92.2% and 96.8%, respectively. Substantial intertechnique agreement (kappa > 0.4) was present in 102 (97.1%) of 105 arterial segments. Substantial interobserver agreement was present in 104 (99.0%) of 105 comparisons for both MDCT angiography and DSA with an average kappa value of 0.84 for CT and 0.78 for DSA. MDCT angiography showed more patent segments than DSA (1192 vs 1091). All nine segments seen on DSA and not seen on MDCT angiography were in the calves. Of 110 segments seen on MDCT angiography and not seen on DSA, 100 (90.9%) were in the calves. CONCLUSION: MDCT angiography was accurate in showing arterial atheroocclusive disease with reliability similar to DSA. MDCT angiography showed more vascular segments than DSA, particularly within calf vessels.

A debate on the value and necessity of clinical trials in surgery.

In the current era of evidence-based medicine there is increasing demand for randomized clinical trials (RCTs) in surgery. Unfortunately, many unique aspects of surgery make RCTs difficult to implement. This article is a debate that explores the motion that clinical trials in surgery are both useful and necessary.