J. P. Fletcher

The role of the fibrocyte in intimal hyperplasia

Summary.  Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow‐derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha‐smooth muscle actin (α‐SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and α‐SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and α‐SMA) and also to double stain for CD34 and α‐SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury.

An increased concentration of rifampicin bonded to gelatin-sealed Dacron reduces the incidence of subsequent graft infections following a staphylococcal challenge

The purpose of this study was to determine if 10 mg/ml rifampicin bonded to gelatin-sealed Dacron (Gelsoft) reduced staphylococcal infection. Grafts soaked in rifampicin were interposed in the left carotid artery of 20 merino sheep and then inoculated with 10(8) colony-forming units of MRSA (10 sheep) or a slime producing Staphylococcus epidermidis (10 sheep). Grafts were harvested at 3 weeks, and perigraft abscess, anastomotic disruption and graft occlusion recorded. Swabs were taken to assess bacterial growth of the perigraft tissues, and external and internal graft surface. Grafts segments were incubated in broth medium. Results were compared with previously published results that used graft that were not soaked in rifampicin (control) and grafts soaked in 1.2 mg/ml rifampicin. A total of 4/50 cultures were positive and significantly reduced for S. epidermidis compared with the control group of 30/50 (P < 0.05) and the 1.2 mg/ml group of 13/45 (P < 0.05). For the methicillin resistant staphylococcus aureus (MRSA) group, 6/40 cultures were positive, which was significantly reduced compared with the control group (38/40, P < 0.05) and the 1.2-mg/ml group (19/32, P < 0.05). In conclusion an increased concentration of rifampicin significantly reduced the incidence of prosthetic vascular graft infection following a challenge of MRSA or S. epidermidis.

Progression of macrovascular disease after transplantation.

INTRODUCTION Cardiovascular and cerebrovascular disease are major causes of morbidity and mortality after kidney transplantation. The aim of this longitudinal study was to examine the natural history of carotid plaque and to determine risk factors for the progression of vascular disease in uremic, type 1 diabetic patients who received a combined kidney and pancreas transplant. METHODS Carotid artery (n=765) and lower limb vascular duplex scanning (n=656) were prospectively undertaken in 82 recipients before transplantation, at 6 months, and then at annual intervals for up to 10 years. Plaque in the internal carotid artery (ICA), external carotid artery, and common carotid artery was classified by type, location, extent, and degree of functional obstruction, and evaluated using multivariate analysis. RESULTS Carotid plaque was present in 22.5% of patients at initial scanning, but increased to 56.6% by 7-10 years after transplantation, especially in the ICA and common carotid artery. Both the severity and extent of plaque increased, and plaque became more complex and heterogeneous with time after transplantation (P<0.001). Carotid plaque was associated with older age, current cigarette smoking, hyperphosphatemia, hypoalbuminemia, duration of pretransplantation dialysis, and presence of lower limb plaque (P<0.05-0.001). The severity of carotid plaque increased in older, hypertensive recipients and was associated with metabolic acidosis and hyperphosphatemia (all P<0.05). Severity of ICA disease correlated with disease in the contralateral ICA (r=0.57, P<0.001) and femoral arteries (r=0.42, P<0.001). Paradoxically, each carotid artery progressed independently of the other. ICA disease severity progressed when heterogenous, calcified, or new plaque was present on scanning, and with reduced renal transplant function (P<0.01-0.001). The mean ICA blood flow remained stable with time but was progressively impaired by hypertension, fasting hyperglycemia, and a lower prednisolone dose (P<0.05). Cerebrovascular events occurred in only four patients and were unrelated to carotid disease, implying relative plaque stability. CONCLUSION Extensive carotid vascular wall abnormalities increased significantly despite kidney and pancreas transplantation. Initiation of plaque was associated with systemic factors, whereas progression of established plaque was largely influenced by local factors within the arterial wall.

A Prospective Randomized Multicentre Comparison of Expanded Polytetrafluoroethylene and Gelatin-Sealed Knitted Dacron Grafts for Femoropopliteal Bypass

PURPOSE To compare graft patency between expanded polytetrafluoroethylene (PTFE) and gelatin-sealed knitted Dacron for femoropopliteal bypass. METHODS A prospective, multicentre trial was performed in 108 patients randomized to receive either a PTFE or Dacron prosthetic graft. Distal anastomosis was above knee in 75 and below knee in 33 patients. RESULTS Primary patency at 1, 2 and 3 years was 72, 52 and 52% for PTFE, and 70, 56 and 47% for Dacron (P = 0.87). Secondary patency at 1, 2 and 3 years was 74, 54 and 54% for PTFE and 78, 70 and 53% for Dacron (P = 0.39). The most significant predictors of early graft failure were poor vessel run-off (P = 0.04) and critical limb ischaemia (P = 0.04). CONCLUSION There was no difference in graft patency between PTFE and Dacron for femoropopliteal bypass.

Effect of leg exercises on popliteal venous blood flow during prolonged immobility of seated subjects: implications for prevention of travel-related deep vein thrombosis

Summary.  Background: Venous stasis is an important contributing factor in the development of travel‐related deep vein thrombosis. This study examined factors affecting popliteal venous blood flow in order to determine the most effective exercise regimen to prevent venous stasis. Methods: Twenty‐one healthy subjects were randomly assigned to various activities over a 9‐week period. Subjects remained seated throughout the investigation and 3660 duplex ultrasound examinations were performed by a single examiner using a SonoSite 180 Plus handheld ultrasound. Baseline popliteal vein blood flow velocity, cross‐sectional area and volume flow in subjects sitting motionless were assessed in the first 3 weeks.The remaining 6 weeks involved subjects performing airline‐recommended activities, foot exercises, foot exercises against moderate resistance and foot exercises against increased resistance in order to determine the most beneficial method for enhancing popliteal venous flow. Sitting with feet not touching the floor and the effect of sleeping were also assessed. Results: The median age of the subjects was 22 years (range: 18–25.5 years), height 171 cm (162.5–180.5 cm) and body mass index 25.3 kg m–2 (23.2–26.3 kg m–2). Blood volume flow in the popliteal vein was reduced by almost 40% with immobility of seated subjects and by almost 2‐fold when sitting motionless with feet not touching the floor. Foot exercises against increased resistance positively enhanced volume flow (P < 0.0001). Conclusion: Leg exercise regimens enhanced popliteal venous flow during prolonged immobility of seated subjects, reinforcing the importance of regular leg movement to prevent venous stasis during prolonged sitting, such as in long‐distance travel.

Prophylaxis against Staphylococcus Epidermidis Vascular Graft Infection with Rifampicin-Soaked, Gelatin-Sealed Dacron

An animal model was used to assess the efficacy of rifampicin-impregnated, gelatin-sealed Dacron in the prevention of vascular graft infections caused by Staphylococcus epidermidis. Under a general anaesthetic an interposition graft was placed into sheep carotid artery. On completion of the operation 1 ml of normal saline containing 10(8) colony forming units (cfu) of a slime-producing S. epidermidis was inoculated directly onto the graft. After 3 weeks the graft was harvested. Swabs were taken of perigraft tissues, and of external and internal aspects of the graft. A 3-5-mm segment of the graft was incubated in broth medium and a second segment was ground for 5 min and incubated in broth medium. The presence of abscess formation and anastomotic disruption was assessed. Ten sheep received a gelatin-sealed Dacron graft (control), while nine received the same graft impregnated with rifampicin at a concentration of 1.2 mg/ml (treated). Eight of 10 control grafts were infected, with 30 of 50 possible cultures positive, compared with four of nine treatment grafts infected (P = 0.13) and 13 of 45 cultures positive (P = 0.004). The control group had four abscesses and two anastomotic disruptions; the treatment group had no abscesses (P = 0.05) or anastomotic disruptions (P = 0.26). Other organisms were isolated from nine of the 12 infected grafts, most commonly Staphylococcus aureus. There was no development of resistance to rifampicin. Rifampicin-impregnated, gelatin-sealed Dacron is successful at reducing the incidence of S. epidermidis vascular graft infection.

Long-term results of saphenous vein graft arteriovenous fistulas

The long-term results of autogenous saphenous vein grafts for vascular access were examined in 70 patients. The cumulative patency rate was 66 percent at 2 years and 40 percent at 3 years. No difference could be detected in the occlusion rate of grafts in patients who received a kidney transplant and those who did not. Intraoperative measurement of blood flow through the grafts did not prove useful as an indicator of long-term patency. No deaths were attributable to the grafts, and major complications were limited to infection in three patients and distal ischemia in two; these complications necessitated ligation of the graft in all five patients.

Improved Outcomes with Endovascular Stent Grafts for Thoracic Aorta Transections

OBJECTIVE To retrospectively assess the outcome of endovascular stent-graft implantation for thoracic aortic transections (ETAT). DESIGN Retrospective review. METHODS 16 patients median age 30 years, treated between May 2000 and April 2007. Median injury severity score was 33 (range 29 to 66) in 14 acute patients; 2 patients had thoracic pseudoaneurysms. The Cook-Zenith endograft was used in eight patients, Medtronic-Talent (6) and Gore-Excluder (2). Average procedure time was 90 minutes, blood loss 100 (range 40 to 3000) mls, screening time 10.8 (range 5.9 to 22.6) minutes, and contrast dose was 195 (range 60 to 400) mls. RESULTS Graft deployment was successful in all cases. There was one death within 30 days. The left subclavian artery was completely covered in one case, and partially in three. Two patients had Type I endoleak, and one delayed Type II endoleak. One patient had iatrogenic right coronary artery dissection. Two patients developed difficult to treat hypertension, and one acute renal failure. CONCLUSION Endovascular intervention is a safe and effective treatment for aortic transection in multiple trauma patients. ETAT reduces the major morbidity and mortality associated with open repair in multiple trauma patients. The majority of these patients are young and long-term follow up is necessary to assess graft durability.

MECHANICAL COMPRESSION IN THE PROPHYLAXIS OF VENOUS THROMBOEMBOLISM

Venous thromboembolism (VTE) is an important cause of morbidity and mortality in a substantial number of the Australian community. There exists a considerable range of potential prophylactic measures aimed at reducing the risk of VTE. These antithrombotic regimens include pharmacological interventions and mechanical techniques to counteract venous stasis including graduated compression stockings and intermittent pneumatic compression (IPC) devices. This review particularly concentrates on evidence for the use of mechanical prophylaxis and the interrelationship with pharmacological methods of VTE prophylaxis. Mechanical and pharmacological methods of VTE prophylaxis are both effective and when used in combination have synergistic effects. Although there are a number of different IPC systems, little evidence is available at present that differentiates these on the basis of VTE prevention. Compliance and patient acceptance of IPC as a preventative measure has improved with miniaturization and device weight reduction. IPC should be used according to recommended guidelines. In moderate‐risk patients when pharmacological prophylaxis is contraindicated, IPC can be used as an alternative. High‐risk patients should receive both mechanical and pharmacological prophylaxis to reduce their relative risk. Until further evidence becomes available, the specific type of IPC unit chosen will generally be determined by ease of use, availability and cost.

Fluoropolymer coated Dacron or polytetrafluoroethylene for femoropopliteal bypass grafting: a multicentre trial

Background:  This trial was designed to compare graft patency between expanded polytetrafluoroethylene (PTFE) and fluoropolymer coated Dacron for femoropopliteal bypass in patients in whom saphenous vein was unavailable.