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Biomedical subjects

M D Colburn

Publications and source records attributed to M D Colburn.

At least 19 recordsLinked to original sources
PubMed1998

Dexamethasone and enalapril suppress intimal hyperplasia individually but have no synergistic effect.

Vascular injury is associated with complex interactions that lead to development of intimal hyperplasia (IH). We have demonstrated previously that the corticosteroid dexamethasone and the ACE-inhibitor enalapril are effective in suppressing the development of IH. We hypothesize that due to distinctly different pharmacologic mechanisms of action, a synergistic effect would be expected if these agents were given in combination. Forty New Zealand White rabbits underwent balloon catheter denudation of the carotid artery. Animals were divided into four equal treatment groups and received daily intramuscular injections: Group 1, saline; Group 2, enalapril 0.07 mg/kg, Group 3, dexamethasone 0.125 mg/kg; and Group 4, enalapril 0.07 mg/kg plus dexamethasone 0.125 mg/kg. Vessels were harvested at 12 weeks and intimal hyperplasia was measured as a ratio of the absolute area of IH to the normalized area enclosed by the internal elastic lamina (IH/IEL). Mean values for IH/IEL are expressed as a percent (SD): Group 1, 32.31 (14.9); Group 2, 9.47 (2.11); Group 3, 5.40 (4.14); and Group 4, 8.49 (4.27). All treatment groups demonstrated significant suppression of IH compared to the control group (p < 0.01); dexamethasone was more effective than enalapril (p = 0.01). There was no statistical difference in IH suppression between respective agents and the combination group (p > 0.10). Coadministration of dexamethasone and enalapril provides no advantage over single-agent therapy in suppressing the development of IH, suggesting that maximal suppression is obtained with single-agent treatment or that these agents affect IH through a common pathway.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Use of the in-situ lesser saphenous vein bypass from popliteal to peroneal artery.

Lesser saphenous vein grafts have become an important element in limb salvage surgery. Their location frequently dictates that the graft be translocated for use. This incurs the disadvantages of ischemia and increased manipulation of the graft and loses the advantages of an in-situ bypass. The use of the lesser saphenous vein as an in-situ graft for tibial artery reconstruction offers the advantages of reduced vein graft injury and improved patency. Technical requirements for an in-situ lesser saphenous bypass include that graft inflow be based on the popliteal artery, the vein length suffice to reach the target artery, and the runoff vessel have adequate size, length, and collateral connections to allow reasonable likelihood of success. The surgical approach requires the patient be in a prone position allowing a posterior longitudinal incision in the leg. Exposure of the distal portion of the peroneal artery is accomplished by separating the peroneus brevis and flexor hallucis longus. The peroneal artery is then visualized when the fibular attachments of the flexor hallucis longus are divided. Our experience indicates that the lesser saphenous vein may be successfully used as an in-situ conduit for bypass to the distal peroneal artery. Technical innovations such as flexible valvulotomes with detachable heads, and tourniquet control of bleeding facilitate the operation. A posterior approach to the popliteal and crural arteries affords the ability to use the lesser saphenous vein as an in-situ bypass.

Aged↗
PubMed1996

Posterior exposure of the popliteal artery in reoperative vascular surgery.

Reoperative vascular surgical procedures play an important role in the successful salvage of ischemic limbs. Such secondary procedures frequently involve difficult situation where the surgical incisions and the vascular anatomy have been compromised by infection of prior surgery. In such instances an alternative surgical approach may provide a significant advantage and aid in successful revascularization. Use of the posterior approach in reoperative vascular surgery is unusual. The application of this exposure may facilitate selected secondary surgical procedures. We review the use of the posterior approach to the popliteal vessels in three patients who required reoperative vascular reconstruction. These cases illustrate the judicious application of this technique and the resultant benefit of this unusual surgical approach.

Aged↗
PubMed1996

Cigarette smoking increases the development of initial 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.

Animals↗
PubMed1995

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.

Adult↗
PubMed1995

Pharmacologic suppression of intimal hyperplasia: a dose-response suppression by enalapril.

Intimal hyperplasia is an exaggerated proliferative response to arterial intimal injury. A successful means of limiting this hyperplastic response would significantly improve patency rates of vascular reconstruction. Angiotensin-converting enzyme (ACE) inhibitors decrease the proliferation and synthetic function of vascular smooth muscle cells in vitro, which have been implicated in the production of intimal hyperplasia. We performed a dose-response study of enalapril to assess the level at which maximal suppression of intimal hyperplasia occurs. Seventy male Sprague-Dawley rats weighing 250-300 grams underwent standardized carotid artery balloon catheter endothelial denudation to induce intimal hyperplasia. Six groups of ten animals each were treated with daily intramuscular injections of one of the following doses of enalapril (mg/kg): 0.025, 0.050, 0.075, 0.100, 0.125, and 0.150. A control group (n = 10) was treated with saline. Injections were started two days before injury and continued for 4 weeks, at which time the injured arteries were pressure-fixed in vivo and harvested. EVG-stained histologic cross-sections were measured by planimetry to determine the amount of intimal hyperplasia, which was calculated as the percentage of the arterial lumen replaced by the lesion. Enalapril suppresses the development of intimal hyperplasia in a dose-responsive manner in this model. No further suppression is achieved above a dose of 0.125 mg/kg.

Animals↗
PubMed1994

The effect of hypofibrinogenemia and fibrinolysis on skeletal muscle function after ischemia and reperfusion.

Isometric contraction to direct supramaximal tetanic stimulation of the anterior tibialis (AT) muscle was measured in 50 New Zealand White rabbits after ischemia and reperfusion. Ischemia was produced unilaterally by collateral ligation and temporary inflow control until AT muscle function decreased to < 5% of contralateral (control) AT muscle and the ischemic interval was recorded. Reperfusion was carried out in one of the following ways: group I (n = 20), release of vascular clamps (blood reperfusion [BR]); group II (n = 10), release of vascular clamps and simultaneous intraarterial administration of 50,000 units of urokinase (urokinase reperfusion [UR]); group III (n = 10), release of vascular clamps and simultaneous administration of 50,000 units of urokinase and 28 mg (5 units) of purified rabbit plasminogen (urokinase plasminogen reperfusion [UPR]); and group IV (n = 10), animals defibrinated to < 50 mg/dl with ancrod prior to ischemia and received BR (ancrod blood reperfusion [ABR]). During reperfusion, function was recorded every 60 min for 2 hr. Recovery of experimental muscle function is expressed as the percentage of contralateral control limb function. The mean ischemic interval (mean +/- SEM), to achieve < 5% of contralateral control limb function, was 206.7 +/- 9.9, 209.5 +/- 16.6, 221.7 +/- 12.5, and 272.0 +/- 14.2 min for animals in groups I-IV, respectively. The mean experimental muscle function (mean +/- SEM) following the ischemic interval was 3.2 +/- 0.8, 4.5 +/- 1.4, 4.4 +/- 1.2, and 3.3 +/- 1.0 for groups I-IV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Afibrinogenemia↗
PubMed1994

Isolated limb thrombolysis with extracorporeal pump and urokinase.

In order to determine the effect of altering the method of delivery of lytic therapy, both hind limbs of 55 adult mongrel dogs were embolized to occlusion and divided into six different treatment groups. Each right limb received 100,000 units of urokinase (UK) intraarterially by one of six different treatment protocols: Group I (n = 10), 5-min infusion with control of arterial inflow (IC); Group II (n = 10), 5-min infusion without IC; Group III (n = 10), 30-min infusion with IC; Group IV (n = 10), 30-min infusion without IC (simulates percutaneous infusion); Group V (n = 10), isolated limb perfusion (ILP) with femoral arterial and venous cannulation and proximal tourniquet control using an extracorporeal circulating pump at a controlled rate and constant temperature (37 degrees C) for 30 min; Group VI (n = 5), underwent ILP without urokinase. A morphometric score was used to quantitate angiographic changes. Films were compared before and after treatment and the net difference for each animal was recorded. [table: see text] We conclude that maintenance of blood flow during urokinase infusion enhances its effectiveness and, contrary to previous recommendations, during intraoperative delivery, inflow should be maintained. Isolated limb perfusion alone was as effective as a 30-min infusion of urokinase without inflow control. Isolated limb perfusion plus UK was by far the most effective method of administering lytic therapy. These experiments suggest that the mechanical action of flowing blood enhances clot dissolution and significantly increases the effectiveness of pharmacologic lysis. Isolated limb fibrinolytic perfusion may have clinical potential in the surgical treatment of limb ischemia.

Angiography↗
PubMed1994

Suppression of intimal hyperplasia in a rabbit model of arterial balloon injury by enalaprilat but not dimethyl sulfoxide.

Intimal hyperplasia appears to result from the deposition of collagen and matrix by medial myofibroblasts, which are stimulated in response to vascular injury. We hypothesized that pharmacologic inhibitors of fibroblast proliferation would suppress the development of intimal hyperplasia. We evaluated the effect of two agents known to inhibit fibroblast proliferation in vitro: enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, and dimethyl sulfoxide (DMSO), an organic solvent. Thirty-five New Zealand white rabbits underwent standardized balloon catheter injury of the left common carotid artery. Experimental groups received daily intramuscular injections of the following: group I (n = 15), saline solution; group II (n = 10), 0.07 mg/kg enalaprilat; and group III (n = 10), 2 ml/kg of a 25% by weight DMSO solution. Injections were started 1 day prior to injury and continued 5 days a week for 8 weeks. Carotid arteries were perfusion-fixed at 12 weeks and cross-sectioned for measurement by planimetry. Intimal hyperplasia was measured as the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina (IH/IEL) and was expressed as a percent. Mean values for IH/IEL were as follows: group I (control), 20.6 +/- 2.3%; group II (enalaprilat), 9.5 +/- 0.7%; and group III (DMSO), 17.6 +/- 2.6%. Enalaprilat-treated animals demonstrated a statistically significant suppression of intimal hyperplasia compared with controls (p < 0.01, ANOVA, Student's t test), whereas the DMSO-treated group did not. We conclude that enalaprilat is effective in suppressing the development of intimal hyperplasia in this model of arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1994

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Abdominal aortic surgery with concomitant congenital renal fusion.

The association between aortic pathology and congenital renal fusion adds little morbidity or mortality to the natural history of either entity. Nevertheless, it complicates the management of aortic pathology, specifically degenerative atherosclerotic disease. The therapeutic goal is to resect the aneurysm or bypass the occlusive segment while preserving renal function. Important principles in the management of these difficult patients include accurate preoperative detection and characterization of the renal abnormality, complete familiarity with the likely anatomic variations associated with this anomaly, adequate exposure of the aortic lesion while preserving renal perfusion, and avoidance of injury to a frequently abnormally located collecting system. In this review we report two cases of abdominal aortic aneurysm associated with congenital renal fusion. The principles of management are thoroughly discussed, and guidelines aimed at facilitating decisions made during the clinical treatment of these difficult patients are suggested.

Aorta, Abdominal↗
PubMed1993

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.

Adult↗
PubMed1993

Benefit of carotid endarterectomy after prior stroke.

PURPOSE: The benefit of carotid endarterectomy (CEA) in preventing recurrent stroke in patients who have sustained a previous stroke remains controversial. The purpose of this study was to evaluate the immediate results and long-term benefit of CEA after recovery from a prior ipsilateral stroke. METHODS: Between 1980 and 1990, 85 patients underwent CEA for prior stroke with an average follow up of 54 months (range 0.3 to 130). The interval from prior stroke to CEA averaged 19.8 months (range 0.1 to 158.3). Vascular risk factors included hypertension in 70.6%, diabetes in 20.0%, history of smoking in 80.0%, and associated coronary artery disease in 51.8% of the patients. RESULTS: There were no perioperative deaths. Four patients (4.7%) had an ipsilateral stroke within 30 days of operation. During the follow up 31 patients (36.5%) died. The leading cause of death was cardiac (54.8%) followed by cancer (16.1%). By life-table methods, the cumulative incidence of recurrent stroke at 9 years was 14% for strokes in the ipsilateral distribution, for an annual stroke risk of 1.6% per year. The cumulative incidence of stroke in other distributions was 5%, for an annual stroke risk of 2.1% per year for all strokes. When interval to operation, preoperative stroke severity, vascular risk factors, and neurologic symptoms were evaluated, no independent indicator of increased risk of recurrent postoperative stroke could be identified. CONCLUSION: These results demonstrate a marked improvement over the natural history and best medical therapy for these lesions as reoperated in the literature. We conclude that CEA is beneficial in preventing recurrent stroke in this group of patients and should be considered the appropriate management in this setting.

Adult↗
PubMed1992

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)

Animals↗
PubMed1992

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)

Animals↗
PubMed1992

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)

Anions↗
PubMed1992

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)

Analysis of Variance↗