Michael D. Colburn

Carotid-Subclavian Bypass for Brachiocephalic Occlusive Disease: Choice of Conduit and Long-term Follow-up

BACKGROUND AND PURPOSE Atherosclerotic disease of the proximal brachiocephalic circulation may produce disabling symptoms referable to cerebral or upper extremity hypoperfusion and embolization. Bypass of occlusive lesions can provide durable relief of symptoms with minimal complications. The ideal conduit for carotid-to-subclavian and subclavian-to-carotid bypass remains controversial, and it is not clear whether the outflow vessel influences patency and survival. METHODS We performed a retrospective analysis of 60 consecutive carotid-to-subclavian and subclavian-to-carotid bypass procedures. Occlusive lesions were documented preoperatively by arteriography. Patency was determined during follow-up by ultrasound or duplex examination. Actuarial patency, symptom-free survival, and overall survival rates were calculated by the life-table method and analyzed by log-rank test. RESULTS Arterial transposition demonstrated the highest long-term patency rate (100.0 +/- 0.0%). Polytetrafluoroethylene grafts demonstrated the highest bypass graft patency rate (95.2 +/- 4.6%), followed by Dacron grafts (83.9 +/- 10.5%) and saphenous vein grafts (64.8 +/- 16.5%). Symptom-free survival paralleled patency rates, but these differences did not achieve statistical significance. While there were no differences in patency or symptom-free survival by outflow vessel, the overall survival of patients with common carotid lesions was significantly lower than that of patients with subclavian lesions (62.7 +/- 12.8% versus 100.0 +/- 0.0%; P < .05). CONCLUSIONS The outflow vessel does not affect long-term patency in carotid and subclavian bypass procedures; however, patients with common carotid disease demonstrate significantly poorer long-term survival. Transposition results in superior long-term patency, with a trend toward lower results for synthetic grafts and relatively poor results for autogenous vein grafts.

Use of an antibiotic-bonded graft for in situ reconstruction after prosthetic graft infections****

We have developed an infection resistant vascular prosthesis by bonding rifampin to Dacron grafts with the use of a collagen matrix release system. The purpose of this study was to determine the efficacy of this antibiotic-bonded graft in resisting infection after an in situ reconstruction of a previously infected prosthetic bypass. Eighty-three adult mongrel dogs underwent implantation of a 3 cm untreated Dacron graft into the infrarenal aorta. This initial graft was deliberately infected, at the time of operation, with 10(2) organisms of Staphylococcus aureus by direct inoculation. One week later, the dogs were reexplored, the retroperitoneum debrided, and the animals randomized to undergo an end-to-end in situ graft replacement with either one of two types of prosthetic grafts: group I (collagen, n = 36) received control collagen-impregnated knitted Dacron grafts; group II (rifampin, n = 47) received experimental collagen-rifampin-bonded Dacron grafts. Each group of animals was then subdivided to receive one of four treatment protocols: (a) no antibiotic therapy, (b) cephalosporin peritoneal irrigation solution (cefazolin 500 mg/1000 ml) during operation and two doses of cephalosporin (cefazolin, 500 mg intramuscularly) postoperatively, (c) treatment as in protocol group b plus 1 week of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily), and (d) treatment as in protocol group b plus 2 weeks of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily). All grafts were sterilely removed between 3 and 4 weeks after implantation. There were no anastomotic disruptions and all grafts were patent at the time of removal.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose responsive suppression of myointimal hyperplasia by dexamethasone

The effect of increasing doses of dexamethasone on the development of myointimal hyperplasia in the rabbit carotid artery was studied by use of a balloon catheter injury model. Seventy New Zealand white rabbits underwent a standardized 2F balloon catheter stripping of the left carotid intima. The animals were randomly assigned to one of seven groups, each receiving daily injections of either saline (group I, N = 10) or graded doses of dexamethasone: 0.025 mg/kg (group II, N = 10); 0.050 mg/kg (group III, N = 10); 0.075 mg/kg (group IV, N = 10); 0.100 mg/kg (group V, N = 10); 0.125 mg/kg (group VI, N = 10); 0.150 mg/kg (group VII, N = 10). Injections were started 2 days before the intimal injury and continued daily, five times a week, for 8 weeks. The vessels were harvested 12 weeks after injury, and the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina was measured as an index of myointimal hyperplasia. Also, at the time of harvest, blood flow (ml/min) was measured and the resistance delta P/flow (mm Hg/ml/min) calculated for each vessel in vivo. Twelve-week patency rates were 60% in the control group I, 90% in groups II and III, and 100% in groups IV, V, VI, and VII. The value for the intimal hyperplasia/internal elastic lamina index, expressed as a percent, was 22.2 +/- 3.7 for control group I, 17.7 +/- 2.1 group II, 14.8 +/- 3.0 group III, 12.8 +/- 2.4 group IV, 11.5 +/- 1.8 group V, 5.4 +/- 1.3 group VI, and 3.9 +/- 1.1 for group VII.(ABSTRACT TRUNCATED AT 250 WORDS)

Very distal bypass for salvage of the severely ischemic extremity

Forty-six bypass grafts to tibial arteries distal to the ankle were performed in 35 patients for salvage of extremities threatened by gangrene or nonhealing ulcers (grade III, category 5) or ischemic rest pain (grade II, category 4). Most patients (80%) were diabetic, with severely calcified arteries, whom previously we would have considered as candidates for primary amputation. All reconstructions were performed with autologous saphenous vein. Inflow was from the common femoral artery in 5 (11%), the popliteal artery in 25 (54%), or the mid-tibial arteries in 16 (35%). Life-table analysis was used to calculate primary patency and limb salvage. Results were analyzed according to origin of inflow, outflow, or configuration of the conduit (in situ saphenous vein, n = 29 [63%], reversed saphenous vein, n = 11 [24%], or nonreversed saphenous vein, n = 6 [13%]). Overall cumulative primary graft patency at 2 years for all grafts was 72%, and the cumulative limb salvage rate was 89% for the same interval. No significant differences were seen in comparing grafts originating from the femoral or popliteal level with those arising from the tibial arteries. No significant differences were noted in graft patency or limb salvage among grafts with a posterior tibial, dorsalis pedis, or plantar artery outflow. No significant difference was noted between in situ saphenous vein grafts and reversed saphenous vein grafts. A significant decreased primary patency was noted for grafts performed with nonreversed, translocated saphenous vein. We conclude that bypass grafts to the ankle or foot vessels are beneficial and should be considered for limb salvage in extremities with gangrene, ischemic ulceration, or ischemic rest pain. In our experience, in situ saphenous vein grafts or reversed saphenous vein grafts performed similarly, whereas nonreversed saphenous vein grafts have a poorer prognosis. Vessel wall calcification requires a modification in technique for performance of these grafts but did not affect long-term performance or limb salvage, and thus should not be considered a contraindication to vascular reconstruction. The operative microscope was used in 61% (28 of 46) of these cases and found useful in creating these delicate anastomoses. Additional follow-up is needed to document the long-term results of these very distal reconstructions.

Inhibition of intimal hyperplasia by photodynamic therapy using photofrin

Photodynamic therapy using photofrin and light energy inhibits human myofibroblast proliferation in cell culture. The purpose of this study is to evaluate its influence on intimal hyperplasia in vivo. Twenty New Zealand White rabbits underwent a standardized intimal injury to both common carotid arteries with a 2 Fr balloon catheter. One week later, half of the animals received photofrin (5 mg/kg) intravenously. The remaining 10 rabbits received no photofrin. Two days later, all neck incisions were reopened and a 1-cm segment of each of the 40 carotid arteries was exposed for 5 min to 80 mW of 630 nm light energy from a continuous wave tunable dye laser (fluence = 7.6 J/cm2). All vessels were harvested 5 weeks post-laser treatment following in vivo fixation with formalin. From each artery, separate cross-sections taken from both the lasered and non-lasered regions of each vessel were mounted and stained for histologic evaluation. Analyzed segments were then divided into four different treatment groups: group I segments consisted of arterial cross-sections which were taken from vessel regions that were injured but received neither photofrin nor laser treatment (group I, n = 20); group II segments also did not receive photofrin but were exposed to light energy (group II, n = 20); group III segments received photofrin but no light energy (group III, n = 20); and cross-sections in group IV were taken from those segments which received both photofrin and laser treatment. Using planimetry, the ratio of the area of intimal hyperplasia (IH) to the area enclosed by the internal elastic lamina (IEL) was measured for each specimen (IH/IEL).(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of neutrophil (PMN) function by heparin, dexamethasone, and enalapril

The aim of this study is to investigate the effect of a seemingly divergent class of pharmacologic agents, each having been reported to suppress intimal hyperplasia, on neutrophil (PMN) function. Human PMNs were isolated and exposed for 30 min to either saline or one of three different pharmacologic agents, each tested at three different concentrations: Group 1, saline (control, n = 14); Groups 2-4, heparin (5000 units, n = 8; 2500 units, n = 6; 1250 units, n = 6) respectively; Groups 5-7, dexamethasone (4 mg, n = 8; 2 mg, n = 6; 1 mg, n = 6), respectively; and Groups 8-10, enalapril (1.25 mg, n = 8; 0.62 mg, n = 6; 0.31 mg, n = 6). Superoxide anion production was measured by the reduction of cytochrome c in a spectrophotometric assay. Chemotaxis was evaluated by the number of PMNs migrating across a filter using a Neuro Probe chamber. Phagocytosis was determined by the ingestion of opsonized zymosan particles by PMNs. Serum obtained from each PMN donor was used both to opsonize the zymosan and as a chemoattractant in the chemotaxis assay. No agent, at any dose, significantly changed superoxide production when compared to control cells. All three agents significantly inhibited PMN chemotaxis at every dose tested (P less than 0.01). In the phagocytosis assay, both heparin (at high and intermediate doses) and enalapril (at all doses) significantly reduced phagocytic activity (P less than 0.01); however, dexamethasone (at high and intermediate doses) produced a marked stimulation (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cigarette smoking increases the development of intimal hyperplasia after vascular injury

PURPOSE Our purpose was to determine whether exposure to cigarette smoke increases the development of intimal hyperplasia (IH) after vascular injury. METHODS Sixteen adult male Sprague-Dawley rats underwent standardized balloon catheter injury of the left common carotid artery. For 4 weeks before and 4 weeks after injury, animals in the experimental group (n=8) were exposed to cigarette smoke with an automated vacuum pump device. Animals in the control group (n=8) were restrained in the smoking device for an identical amount of time and underwent arterial injury at 4 vivo, prepared as histologic cross sections, and stained for elastin. IH was measured by planimetry and is reported both as the absolute area of IH and as the ratio (IH/IEL) of the absolute area of IH to the normalized area enclosed by the internal elastic lamina (expressed as a percent). RESULTS The absolute area of IH was 2.09 +/- 0.34 for the experimental group compared with 0.94 +/- 0.25 for the control group; mean IH/IEL was 43% +/- 7.1% for the experimental group versus 17.7% +/- 4.7% for the control group (p < 0.05, two tailed unpaired t test. CONCLUSIONS Inhalation of cigarette smoke increases the development of intimal hyperplasia in a rat model of a balloon catheter arterial injury.

Endovascular Repair of Abdominal Aortic Aneurysms Using the EGS Tube and Bifurcated Graft Systems

Abstract. Left untreated, aneurysmal disease of the abdominal aorta is a highly lethal condition. Standard transabdominal repair of aortic aneurysm, although successful and durable, continues to be plagued by significant morbidity, mortality, and cost. Placement of an endovascular graft through a femoral arteriotomy is a new technique that could potentially reduced this morbidity and cost without sacrificing efficacy. This report details the development of a U.S. Food and Drug Administration (FDA)-approved endovascular grafting device. In addition, we describe our experience screening patients and summarize our clinical experience with the placement of both tube and bifurcated endovascular graft systems. To date, 16 patients have undergone endovascular repair with a tube graft at UCLA, and three bifurcated grafts have been placed. Two patients required conversion to conventional open aneurysm repair. All the remaining procedures were successful, and there were no perioperative deaths or major complications. We conclude that endovascular grafting of aortic aneurysms is both feasible and safe. Long-term patency and the ability of this technique to prevent the known complications of aortic aneurysmal disease remain unanswered questions at this time.

Standardization of skeletal muscle ischemic injury

Observations on skeletal muscle function after a timed ischemic interval suggests significant interanimal variability. The purpose of this study is to compare the use of function versus time as a method for standardizing the degree of ischemic injury. Muscle function was measured by recording the isometric contraction to direct supramaximal tetanic stimulation of the anterior tibialis muscle (AT). Muscle cell viability was determined by the reduction of triphenyltetrazolium chloride (TTC)/g tissue measured by a spectrophotometric assay. Twenty-four New Zealand White rabbits underwent an interval of ischemia to one anterior tibialis muscle produced by collateral ligation and unilateral inflow control, using the contralateral AT as a control. The duration of ischemia was determined by one of three methods: Group I, n = 8, underwent ischemia for 3 hr (3 hr); Group II, n = 8, underwent ischemia until AT muscle function decreased to 20% of control (20%); and Group III, n = 8, underwent ischemia until AT muscle function decreased to less than 5% of control (less than 5%). Following the ischemic injury, both physiologic function and cellular viability were measured and expressed as a percentage of control. After 3 hr of ischemia, the mean function was 15.5 with a standard deviation of 20.2, and the TTC reduced/g tissue was 24.7 with a standard deviation of 24.8. When the ischemic interval was determined by a decline of muscle function to 20% of control, the mean TTC reduced was 33.4 +/- 7.6. The mean TTC reduced, when the ischemic interval was terminated when muscle function reached less than 5% of control, was 13.5 +/- 7.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous postoperative intra-arterial urokinase infusion in the treatment of no reflow following revascularization of the acutely ischemic limb

The loss of distal tissue perfusion sufficient for limb salvage following restoration of inflow to an acutely ischemic extremity has been referred to as the “no-reflow” phenomenon. We hypothesized that patients with no reflow and limb-threat ischemia might benefit from prolonged postoperative intra-arterial infusion of the thrombolytic agent urokinase (UK). Twelve patients with arteriographic and clinical evidence of no reflow following a lower extremity arterial thrombectomy and/or bypass procedure were treated with a continuous intra-arterial UK infusion in the immediate postoperative period. The mean duration of UK infusion was 47 hours (range 15 to 112 hours). The mean rate of infusion was 58,000 units/hr (range 30,000 to 100,000 units/hr). Seven patients required transfusion for bleeding from the treated extremity (mean 3.4 units packed cells) and one required reoperation for a groin hematoma. Plasma fibrinogen levels remained within the normal range in all patients, and no systemic bleeding complications were encountered. The intra-arterial UK infusion resulted in limb salvage in 7 of 12 patients. Six patients have viable, functional extremities at a mean follow-up interval of 24.9 months (range 6.4 to 49.7 months). One patient required below-knee amputation 6 months after treatment for progressive ischemia. The other five patients required below-knee amputation during the same hospitalization after UK failed to restore distal perfusion. The postoperative period is widely considered to be a contraindication to thrombolytic therapy. Our experience indicates that while UK may cause bleeding from the treated extremity, which in some cases requires transfusion, there is no evidence of systemic fibrinolysis or systemic hemorrhage. We conclude that the salvage of otherwise nonviable limbs by prolonged postoperative intra-arterial UK infusion is possible. This observation supports the theory that the no-reflow phenomenon is due, in part, to distal intravascular fibrin deposition.