Update on gene therapy for intimal hyperplasia.

Trauma to the vessel wall leads to smooth muscle cell (SMC) activation and eventual intimal hyperplasia. This process occurs in restenosis following balloon angioplasty, particularly with stent placement, occlusion of vascular bypasses, and arteriopathy of chronic allograft rejection. Genetic interventions affecting the cell cycle or early postinjury events have been successful in limiting SMC proliferation in vitro and in animal models. Gene therapy strategies have included the use of antisense oligonucleotides to block protein synthesis, transduced genes to cause cytotoxicity, and genetically engineered cells to decrease the response to injury. The clinical application of gene therapy in vascular diseases should follow the evolution of delivery systems that enable efficient local gene transfer to the arterial wall. (Tab. 1, Fig. 1, Ref. 30.)

New, angle-independent, low cost Doppler system to measure blood flow.

BACKGROUND: A new Doppler flowmeter using a special transducer forming two ultrasound beams to insonate vessels was developed. This low-cost flowmeter allows the flow to be measured independently of the angle of insonation. METHODS: Sixty-five flow determinations were made in the carotid arteries of five pigs. The flowmeter measured the flow in an artery bled into a calibrated vessel. Results were compared with the true volume of the blood captured. RESULTS: On average, 13 measurements per animal were made at different flow rates (80 to 600 mL/min). The flowmeter measured flow-volume rates in mL/min were found to be within +/- 15% of the cylinder captured volume. CONCLUSIONS: The accuracy of the angle-independent flowmeter is comparable with that of flowmeters currently used clinically. The small size and portability, low operator dependency, and low cost suggest potential for continuous acute and chronic-flow monitoring and a potential for an implantable flow-monitoring device.

Complex venous reconstruction for chronic iliofemoral vein obstruction.

A 35-year-old patient, physically very active, developed symptoms and signs of postphlebitic venous obstruction in the right lower extremity that was complicated by deep venous thrombosis, while recovering from a motorcycle accident. Duplex and venography demonstrated occlusion of the right superficial femoral vein and right external iliac vein. Strain-gauge plethysmography and measurements of venous pressures demonstrated functional obstruction. The patient underwent saphenous cross-femoral vein bypass, right saphenous-popliteal anastomosis accompanied with distal posterior tibial to saphenous vein arteriovenous fistula. Ten days following surgery, the arteriovenous fistula and the distal great saphenous vein closed spontaneously. The rest of the reconstruction remained patent as documented by duplex up to 24 months following the surgery. Clinically, the patient is doing well, tolerating heavy physical exertion as before his accident. The importance of selection of patients for venous bypass surgery is stressed. Only patients with co-existing anatomical and functional obstruction are good candidates for these procedures.

Increased arterial inflow in extremities with chronic venous insufficiency: an important and unappreciated hemodynamic parameter.

BACKGROUND: The purpose of this study was to evaluate and analyze arterial inflow (AI) in lower extremities of patients with symptoms of chronic venous insufficiency (CVI) and of members of a healthy control group. METHODS: Foot mercury-in-silicon strain-gauge plethysmography was used to measure AI, venous reflux, and muscle pump efficiency in 388 extremities of 194 patients with symptoms of CVI. Severe stage III symptoms (Society for Vascular Surgery/International Society for Cardiovascular Surgery classification) were present in 84 extremities, moderate stage II symptoms were present in 81 extremities, and mild stage I symptoms were present in 158 extremities. No symptoms, stage 0, were found in 65 contralateral extremities of patients with unilateral symptoms. Identical parameters were measured in 70 extremities of 35 healthy subjects in a control group. AI in each staged group was compared with that of the control group and with that of the other groups with symptoms with the use of Kruskall-Wallis analysis of multiple variances. RESULTS: The mean AI (+/-SD) in milliliters per 100 ml of foot tissue per minute in the extremities in the control group was 0.82 +/- 0.48. In the extremities without symptoms, contralateral to those with symptoms in patients with unilateral disease, the AI was 1.24 +/- 0.88. In extremities with mild symptoms the AI was 1.54 +/- 1.20, in extremities with moderate symptoms it was 2.88 +/- 1.70, and in extremities with severe symptoms it was 6.25 +/- 4.91. The AI was significantly increased in all extremities of patients with CVI (stages 0 to III) when compared with that of patients in the control group. Extremities with stage II and III disease had significantly higher AI than did extremities with stage 0 and stage I disease. The difference in AI between extremities with stage 0 and I disease was not statistically significant, and no significant difference in AI was seen between extremities with stage II and III disease. CONCLUSIONS: When plethysmographic methods are used to evaluate extremities with CVI, high AI, if not considered, can overrepresent the true magnitude of reflux. High AI may indicate presence of primary anatomic arterioventricular fistulas, or it may be the consequence of inflammatory changes and secondary functional arterioventricular shunting. Increased AI in contralateral extremities with no symptoms may point to the role of high flow in the pathogenesis of CVI. Clarification of this question requires further investigation.

A comparison of conservative therapy and early selective ligation in the treatment of lymphatic complications following vascular procedures.

BACKGROUND: Lymphatic leakage is a relatively uncommon but serious complication following vascular procedures. A conservative approach consisting of bed rest, leg elevation, prophylactic antibiotics, compressive dressings, and intermittent aspiration is the most commonly used treatment. Because of the long time it takes to cure this condition and the potential for infections, a more aggressive approach consisting of wound exploration and ligation of the leaking lymphatic has been proposed. We review our experience of the past 3 years treating 17 of these complications by using 1 of these 2 approaches. PATIENTS AND METHODS: Seventeen groin complications were seen over a period of 3 years. Ten (59%) patients were treated by selective ligation assisted with isosulfan blue dye injection, and the remaining 7 (41%) were treated conservatively. RESULTS: Mean hospital stay was 2.4 days (range 1 to 4) for the operative group versus 19 days (range 14 to 42) for the conservative group. One complication was seen in the operative group, whereas 4 (57%) patients developed groin infections following conservative therapy. One (10%) patient developed a recurrence following ligation that was treated successfully by reoperation. CONCLUSION: Our experience with the use of surgical ligation of leaking lymphatic assisted by isosulfan blue, when compared with conservative treatment, has led to a decrease in hospital stay, lower complication rates, and fewer recurrences. In our view, this approach represents the best form of treatment for postoperative groin lymphatic complications.

Varicose vein surgery with preservation of the saphenous vein: a comparison between high ligation-avulsion versus saphenofemoral banding valvuloplasty-avulsion.

PURPOSE: Surgical treatment of varicose veins with preservation of the greater saphenous vein (GSV) was studied. METHODS: Patients with reflux at the saphenofemoral junction and grossly normal GSV were treated with two different surgical techniques: perivalvular banding valvuloplasty (PVBV-A) of the saphenous valve, wherein the diameter of the uppermost saphenous valve was narrowed by Dacron-reinforced silicone band (12 patients, 15 extremities); and high ligation (HL-A) of the saphenous vein, wherein the GSV was ligated flush with the femoral vein (14 patients, 16 extremities). Both groups also had varicose tributaries of GSV avulsed through multiple stab incisions. RESULTS: In the HL-A group two GSV (13%) remained completely patent, 10 GSV (62.5%) thrombosed partially, and the remaining four GSV (25%) had complete thrombosis. In the PVBV-A group 12 GSV (80%) remained completely patent and without reflux, one GSV (7%) remained patent but showing reflux. Two GSV (13%) thrombosed completely. There were no surgical complications or recurrences (mean follow-up was 9.4 months for PVBV-A and 9.5 months for HL-A), and the postoperative recovery time was similar for both groups. CONCLUSIONS: Both techniques are equally effective in the early elimination of varicosities. Preservation of the saphenous vein is significantly better after PVBV-A (p < 0.01). A prospective randomized trial with long-term follow-up is required.

Treatment of angioaccess-induced ischemia by revascularization.

Upper extremity ischemia related to the construction of a chronic angioaccess is a serious and occasionally devastating complication. Fourteen patients with end-stage renal disease (mean age 58 +/- 18 years, 13 with diabetes, 10 female) had ischemia after construction of an angioaccess. Twelve patients had a polytetrafluoroethylene brachioaxillary bridge arteriovenous fistula (BAVF), one patient had a radiocephalic arteriovenous fistula (AVF) and one patient had a brachiocephalic AVF. All patients had severe ischemia and five of them had established gangrenous changes. Symptoms appeared immediately after construction of the access in 10 patients. The remaining four patients had late onset of ischemia. The technique used for revascularization in all of these patients consisted of ligating the artery just distal to the takeoff of the AVF or BAVF and establishing an arterial bypass from a point proximal to the AVF or BAVF inflow to a point distal to the ligature. Bypass grafts consisted of saphenous vein in 13 cases and polytetrafluoroethylene in one case. Thirteen patients had a complete recovery, including healing of gangrenous lesions. One patient with severe gangrene of the hand at the time of revascularization required forearm amputation 13 months later because of progressive occlusive arterial disease. All AVFs were patent at 1 year. The 1-year patency rate for the BAVFs was 81.7%. All arterial bypasses were patent at 1 year. It is concluded that this technique offers consistent and durable hemodynamic and clinical improvement in arms affected by access-induced ischemia, with minimal morbidity, and does not affect the longevity of the angioaccess.