Physiological, physical and behavioural changes in dogs (Canis familiaris) when kennelled: testing the validity of stress parameters.

Domestic dogs (Canis familiaris) housed in kennelling establishments are considered at risk of suffering poor welfare. Previous research supporting this hypothesis has typically used cortisol:creatinine ratios (C/Cr) to measure acute and chronic stress in kennelled dogs. However, the value of C/Cr as a welfare indicator has been questioned. This study aimed to test the validity of a range of physiological, physical and behavioural welfare indicators and to establish baseline values reflecting good dog welfare. Measurements were taken from 29 privately-owned dogs (14 males, 15 females), ranging in age and breed, in their own home and in a boarding kennel environment, following a within-subjects, counterbalanced design. Pairwise comparisons revealed that C/Cr and vanillylmandelic acid:creatinine ratios (VMA/Cr) were higher in the kennel than home environment (P=0.003; P=0.01, respectively) and were not associated with differences in movement/exercise between environments. Dogs' surface temperature was lower in kennels (P=0.001) and was not associated with ambient temperature. No association with age, or effects of kennel establishment, kennelling experience, sex or source were found. Dogs were generally more active in kennels, but showed considerable individual variability. C/Cr and 5-HIAA:creatinine ratios (5-HIAA/Cr) were negatively correlated with lip licking in kennels. Baseline values for each parameter are presented. The emotional valence of responses was ambiguous and no definitive evidence was found to suggest that dogs were negatively stressed by kennelling. It was concluded that C/Cr and, particularly, VMA/Cr and surface temperature provide robust indicators of psychological arousal in dogs, while spontaneous behaviour might be better used to facilitate interpretation of physiological and physical data on an individual level.

An expanded series of distal bypass using the distal vein patch technique to improve prosthetic graft performance in critical limb ischemia.

OBJECTIVES: The endovascular first approach has led to increasing complexity for surgical bypass especially in those patients without autogenous conduit. The use of vein interposed at the distal anastomosis has been reported to improve the results of prosthetic grafts. This series expands our initial experience with the distal vein patch technique (DVP) reporting a larger cohort with enhanced follow-up. DESIGN: A retrospective review of prospectively collected data was performed for distal bypasses from July 1995 to November 2008. MATERIALS/METHODS: 1296 tibial bypasses were performed with 270 using the DVP technique. Patient demographics included; 49% diabetes, 20% chronic renal failure, 33% prior failed bypass. Indications for revascularization were claudication (9.3%), rest pain (27.8%), gangrene (22.2%), and non-healing ulceration (40.7%). Lack of vein for the bypass conduit resulted from previous failed grafts (55%), coronary bypass (18%), poor quality vein (23%), or prior vein stripping (8%). Follow-up ranged from 1 to 48 months with graft surveillance by pulse exam, ABI, and Duplex ultrasound. Primary patency and limb salvage ± SE were determined by Kaplan-Meier life-table analysis using Rutherford criteria. RESULTS: Bypasses originated from the external iliac (29%), CFA (55%), SFA (13%), popliteal (1%), and prior grafts (2%). Recipient arteries were below knee popliteal (6%), anterior tibial (25%), posterior tibial (30%), and peroneal (39%). Perioperative graft failure occurred in 13 cases with a total of 41 graft failures leading to 39 major amputations. Primary graft patency from one to four years was 79.8%, 75.6% 65.9%, and 51.2%. Corresponding limb salvage rates were 80.6%, 78.0%, 75.7%, and 67.5%. CONCLUSION: Although not addressed by a randomized trial, we believe this expanded series is a more accurate reflection of expected results confirming that the DVP bypass leads to reasonable long-term results for those challenging patients that require prosthetic distal bypass for lower extremity revascularization.

Tibial bypass for limb salvage using polytetrafluoroethylene and a distal vein patch.

OBJECTIVE: Tibial artery bypass for limb salvage may be required in patients without adequate autogenous vein. The interposition of venous tissue at the distal anastomosis has been advocated to improve the results of prosthetic grafts to tibial arteries. Having reported on technical feasibility and an early experience with polytetrafluoroethylene (PTFE) and a distal vein patch (DVP), we examine the results of this technique with 4-year follow-up. METHODS: From July 1993 to July 1999, 514 tibial bypass grafts were performed, with 80 bypass grafts in 79 patients with PTFE/DVP as the conduit. Patient demographics included 39 men and 40 women (mean age, 67 years); 42 had diabetes mellitus (53%), 16 had renal failure (20%), and 48 had Eagle criteria for increased cardiac risk (60%). Indications for revascularization were rest pain in 39 (49%) and tissue loss in 41 (51%). Lack of adequate vein resulted from previous failed lower extremity bypass graft (47 [59%]), previous coronary bypass graft (21 [26%]), unsuitable vein (8 [10%]), and absent vein due to ligation and stripping (4 [5%]). Follow-up ranged from 1 to 48 months. Results are reported as primary patency or limb salvage +/- SE. RESULTS: Bypass grafts originated from the common femoral artery (40 [50%]), the superficial femoral artery (6 [8%]), and the external iliac artery (34 [43%]). Recipient arteries included anterior tibial (17 [21%]), posterior tibial (28 [35%]), and peroneal (35 [44%]). Four-year primary patency and limb salvage rates were 62.89% +/- 10.6% and 79.21% +/- 8.45%, respectively. There was a 24% mortality rate during the follow-up period. Acute failure occurred in 7 grafts with 5 immediate amputations and 2 revisions. A total of 17 grafts failed during the follow-up period, leading to 11 amputations. CONCLUSION: The DVP technique allows PTFE bypass grafts to tibial arteries with acceptable long-term patency and limb salvage.

Vascular reconstructive options in the ischemic foot.

Aggressive evaluation and treatment of the patient suffering from lower-extremity ischemia is critical. Vascular reconstruction can be performed to enhance healing and to decrease the incidence of major limb amputation and therefore return these patients to active and productive life.

Insulin-like growth factor-1 receptors mediate infragenicular vascular smooth muscle cell proliferation in response to glucose and insulin not by insulin receptors.

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation is an early event in the pathogenesis of atherosclerosis. Insulin and glucose are known to stimulate the growth of VSMC. Cell membrane receptors play an important role in the proliferation of VSMC in response to growth factors. Insulin and insulin-like growth factor-1 (IGF-1) have demonstrated a cross reactivity for receptor binding and function. By using monoclonal antibodies directed against insulin (IRA) and IGF-1 (IGF-1RA) receptors, we attempt to further delineate the mechanism for the proliferation of VSMC in response to insulin and glucose. METHODS: Human infragenicular VSMC isolated from diabetic patients undergoing below-knee amputations were used. Cells from passages 3 to 6 were grown in serum-free media with a glucose concentrations of 0.1% or 0.2%, both with and without insulin (100 ng/mL). The baseline cell density was 4,635 +/- 329 cells/mL. IRA or IGF-1RA was added to the media, with the control group receiving neither antibody. Cells were grown in 5% CO2 at 37 degrees C for 6 days. Analysis of variance was used for statistical analysis, with P <0.05 considered significant. In addition, DNA synthesis was measured using thymidine incorporation assays in the same groups of cells receiving IRA, IGF-1RA, and no antibody. RESULTS: IGF-1RA prevented the proliferation of VSMC in response to insulin and glucose, while IRA had no effect on cell growth. There was no significant growth when IGF-1RA was added to the media, while the control group and the group receiving IRA demonstrated significant growth compared with the baseline concentration of 4,635 +/- 329 cells/mL at all concentrations of insulin and glucose. [3H]thymidine incorporation assays confirmed the cell count results. CONCLUSIONS: These results suggest that the mitogenic effects of insulin and glucose on infragenicular VSMC are due to stimulation of the IGF-1 receptor. VSMC antiproliferative strategies employing receptor blockade should be directed against the IGF-1 receptor, not the insulin receptor.

The additive effects of glucose and insulin on the proliferation of infragenicular vascular smooth muscle cells.

PURPOSE: Peripheral vascular disease involving the infragenicular arterial tree is common in patients with diabetes mellitus (DM). Accelerated proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis. Insulin and glucose stimulate VSMC proliferation and are elevated in patients with non-insulin-dependent DM. We have previously described the mitogenic effect of insulin on VSMCs in vitro; the effects of insulin and glucose separately and in combination on the proliferation of VSMCs grown in serum-free media were studied. METHODS: Human infragenicular VSMCs isolated from diabetic patients with end-stage peripheral vascular disease undergoing below-knee amputation were used. Cells from passages 3 to 5 were grown in serum-free media with varying glucose (0.05%, 0.1%, 0.2%, 0.4%, 0.6%, and 0.8%) and insulin (no added insulin, 100 ng/mL, and 1000 ng/mL) concentrations for 6 days. RESULTS: Insulin stimulated VSMC growth at glucose concentrations more than 0.2% (0.4% glucose with no added insulin resulted in 13,073 +/- 336 cells/mL, 0.4% glucose with 100 ng/mL insulin resulted in 16,536 +/- 1175 cells/mL, 0.4% glucose with 1000 ng/mL insulin resulted in 17,500 +/- 808 cells/mL, 0.6% glucose with no added insulin resulted in 14,167 +/- 1062 cells/mL, 0.6% glucose with 100 ng/mL insulin resulted in 18,984 +/- 1265 cells/mL, 0.6% glucose with 1000 ng/mL insulin resulted in 20,450 +/- 1523 cells/mL, 0.8% glucose with no added insulin resulted in 15, 853 +/- 1650 cells/mL, 0.8% glucose with 1000 ng/mL insulin resulted in 26,302 +/- 1919 cells/mL; P <.05 compared with glucose with no added insulin). Glucose stimulated VSMC proliferation up to a concentration of 0.2% (42% and 117% higher growth at 0.1% and 0.2% glucose, respectively, compared with the baseline, P <.05), regardless of the insulin concentration in the media. The greatest growth (26,302 +/- 1919 cells/mL) occurred in the group with the highest concentration of both insulin (1000 ng/mL) and glucose (0.8% glucose; P <.05). CONCLUSION: Both insulin and glucose stimulate the growth of diabetic infragenicular VSMCs. The mitogenic effects of insulin and glucose are additive and may contribute to the development of atherosclerosis in patients with DM.

Myointimal hyperplasia: basic science and clinical considerations.

The mechanical injury caused by a bypass procedure or angioplasty of the coronary or peripheral arteries can initiate and maintain the process of myointimal hyperplasia. Myointimal hyperplasia is of great clinical importance. The development of the hyperplastic lesion at the outflow anastomosis of a prosthetic bypass or in autogenous saphenous vein bypass placed in the arterial system is responsible for most bypass failures. It is also the primary cause of restenosis after coronary angioplasty. Myointimal hyperplasia is a complex pathological process of the vascular system characterized by an abnormal proliferation of smooth muscle cells of the vascular wall. Proliferating smooth muscle cells migrate to the subendothelial area and form the hyperplastic lesion, which causes stenosis and obstruction of the vascular lumen. The pathogenesis of myointimal hyperplasia remains under investigation. However, it has been established that both mechanical and chemical factors may induce this process. Arterial injury is believed to stimulate the production of growth factors, such as platelet-derived growth factor (PDGF), which have been shown to stimulate the proliferation of arterial smooth muscle cells and the formation of the hyperplastic lesion in the vascular system. These growth factors and cytokines have been found to be secreted by a variety of cells, including endothelial cells, macrophages, platelets, and arterial smooth muscle cells. Blocking the effects of growth factors such as PDGF or fibroblast growth factor (FGF), by the administration of their antibodies, has been shown to limit the development of the hyperplastic lesion. In this article, we begin with the basic physiology of myointimal hyperplasia. We then address possible therapeutic considerations for the future.

Peptide growth factors and signal transduction.

Cell differentiation and proliferation are influenced by peptide growth factors. These peptide molecules are important in maintaining the normal development and growth of animal cells; in addition, they have been found to play a major role in disease states. The role of growth factors in the development of arteriosclerosis and intimal hyperplasia is of great interest to us as physicians taking care of patients with peripheral vascular disease. Factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), insulin, insulin-like growth factor-I (IGF-I), and transforming growth factors alpha and beta (TGF alpha and beta) have been found to play important roles in controlling the progression of cells in the cell cycle. Furthermore, various growth factors have been found to influence the motility of cells, particularly vascular smooth muscle cells (VSMCs).

Spinal cord protection during surgical procedures on the descending thoracic and thoracoabdominal aorta: a critical overview.

During the past three decades, significant advances have been made in the surgical treatment of the diseases affecting the aorta. Despite these important advances, paraplegia remains a devastating complication of the surgical procedures on the thoracic and thoracoabdominal aorta. Paraparesis and paraplegia occur as a direct result of the interruption of blood flow to the spinal cord during the surgical procedures. A number of techniques have been advocated for the prevention of spinal cord ischemic injury. This article critically reviews our current understanding of the extent of this problem, the mechanism of injury, and the methods that have been devised to reduce the frequency of paraplegia following surgical procedures on the descending aorta.

The effect of occult diabetic status and oral glucose intake on brachial artery vasoactivity in patients with peripheral vascular disease.

Brachial artery vasoactivity is a well known non-invasive method of assessing arterial endothelial function in vivo. Brachial artery vasoactivity has been found to be impaired in overt diabetes and in patients with coronary artery disease. Impaired brachial artery vasoactivity is felt to be an early indicator of atherosclerosis. The authors identified a group of patients with lower extremity peripheral vascular disease, who had normal fasting glucose level and were not known to be diabetics. An oral glucose tolerance test was performed in this group of patients. Brachial artery vasoactivity was assessed at each step of the oral glucose tolerance test to examine their occult diabetic status and correlate brachial artery vasoactivity to that status. The authors studied 23 randomly selected patients from the vascular surgery clinic between the ages of 50 and 79 years. Serum glucose level was assessed after a 10-h fast and at 30, 60 and 120 min after a 75-g oral glucose challenge. Any patient with two serum glucose values > 140 mg/dl was considered to have a positive oral glucose tolerance test. Using duplex ultrasound, the brachial artery diameter (cm) and blood volume (ml/min) were assessed before and after tourniquet occlusion at each step of the oral glucose tolerance test. Paired and unpaired t-tests were used to evaluate the results, P < 0.05 was considered significant. Nine patients had abnormal oral glucose tolerance test for a prevalence of 39%. There was no significant difference in fasting glucose levels between positive and negative oral glucose tolerance test patients (97.4+/-16.7 versus 88.5+/-5.8, P = 0.23). Patients with a positive oral glucose tolerance test had impaired vasoactivity at fasting and at each step of the test with no significant changes in brachial artery diameter or blood flow in response to brachial artery occlusion. Patients with a negative oral glucose tolerance test exhibited increased brachial artery diameter at fasting in response to brachial artery occlusion (0.43+/-0.02 versus 0.46+/-0.02, P = 0.03), but not after oral glucose challenge. In patients with a negative oral glucose tolerance test, brachial artery flow volume increased significantly in response to hyperemia at fasting (240+/-61 versus 578+/-262, P = 0.001) and at 30 min after glucose intake (260+/-53 versus 358+/-72, P = 0.01). At 60 and 120 min after glucose intake, brachial artery flow volume did not significantly increase in response to brachial artery occlusion. These results indicate that individuals with PVD and normal fasting glucose levels have a high prevalence of positive oral glucose tolerance test (39%). Patients with normal fasting glucose levels and abnormal oral glucose tolerance test have impaired brachial artery vasoactivity at fasting and after oral glucose challenge, this is in contrast to patients with normal oral glucose tolerance test who have normal fasting hyperemic response to brachial artery occlusion. However, this normal brachial artery vasoactivity is lost in the negative oral glucose tolerance test group in response to oral glucose load. These results suggest that endothelial function in diabetics is impaired in the early stages of the disease even before overt hyperglycemia occurs. Tight control of blood glucose level in glucose-intolerant patients prior to occurrence of overt fasting hyperglycemia may prove protective.

Prosthetic bypass with a distal vein patch for limb salvage.

BACKGROUND: Certain patients require tibial bypass for limb salvage without adequate vein available as the conduit. Polytetrafluoroethylene (PTFE) bypasses result in decreased patency prompting the addition of venous tissue at the distal anastomosis as cuffs, collars, and boots. We assessed feasibility and graft patency of a distal vein patch (DVP) interposed between PTFE and the tibial artery. METHODS: Between 7/93 and 7/96, 148 tibial bypasses were performed with 25 (17%) using PTFE/DVP as the conduit. Patient demographics (n = 24) were 11 males and 13 females, mean age of 67, diabetes (n = 15, 57%), renal failure (n = 8, 31%), and excessive cardiac risk (n = 20, 83%). All patients had limb-threatening ischemia with rest pain in 14 (58%) and gangrene/nonhealing ulcer in 10 (42%). Lack of vein was due to previous failed bypass (15,63%), cardiac surgery (5,21%), and unsuitable vein (4,21%). Patients were discharged on coumadin with follow-up at 1 month, 6 months, and annually. RESULTS: PTFE/DVP bypasses originated from the CFA (13,48%), the SFA (3,11 %) and the external iliac artery due to previous groin dissection (9,41 %). Recipient arteries included anterior tibial (7), posterior tibial (8), and peroneal (10). Follow-up ranged from 1 to 36 months. Cumulative graft patency at 6 months and 3 years was 91% and 78%, respectively, by life table analysis. Limb salvage was 91%. CONCLUSION: These early data indicate that tibial bypass with PTFE/DVP as the conduit results in acceptable patency and limb salvage. In the patient without adequate vein, PTFE bypasses to tibial arteries for limb salvage may be improved with a distal vein patch.

Transforming growth factor beta 1 inhibits the proliferative effect of insulin on human infragenicular vascular smooth muscle cells.

PURPOSE: The distribution of atherosclerotic arterial disease in diabetes mellitus characteristically involves the infragenicular arterial tree including the anterior tibial, posterior tibial, and peroneal arteries. The proliferation of vascular smooth muscle cell (VSMC) is essential in the development of the atherosclerotic lesion. It has long been held that insulin plays a causative role in the formation of the atherosclerotic lesion in diabetes. We studied the role played by insulin in the proliferation of these cells in culture and the interaction of insulin with transforming growth factor beta 1 (TGF beta 1), a factor known for its possible inhibitory effects. METHODS: We have grown and characterized a line of VSMC harvested from atherosclerotic infragenicular arteries of human subjects undergoing below-knee amputation. The cultures were defined as being of VSMC origin by immunohistochemical staining with alpha-smooth muscle actin. Confluent cultures of passages 4 through 7 were seeded into six well plates at a density of 5000 cells/well. After serum deprivation the cells were exposed to insulin (100 ng/ml) alone or in combination with TGF beta 1 (6 ng/ml). RESULTS: Our findings indicate that a 48-hour incubation with insulin augments the proliferation of human infragenicular VSMC, producing a 207% increase in cell number when compared with control cells (11,328 +/- 686, n = 56 vs 3682 +/- 182, n = 87; p < 0.0001). The addition of TGF beta 1 in combination with insulin abolished the accelerated growth rate seen in test groups treated with insulin alone (3614 +/- 247, n = 32 vs 11,328 +/- 686, n = 56; p < 0.0001). CONCLUSION: These results strongly suggest that insulin is a potent stimulant of human infragenicular VSMC proliferation. The mitogenic effect of insulin is inhibited by TGF beta 1, producing proliferation rates comparable to those observed in control cells incubated with serum-free media.

Proliferation and extracellular matrix production by human infragenicular smooth muscle cells in response to interleukin-1 beta.

PURPOSE: Atherosclerotic peripheral vascular disease commonly involves the infragenicular arterial tree. Our study evaluated the effect of interleukin (IL)-1 beta on the proliferation of vascular smooth muscle cells (VSMCs) derived from atherosclerotic infragenicular arteries of human subjects who underwent below-knee amputation, as well as the role of IL-1 beta in VSMCs' production of extracellular matrix components, substances that are important in the transformation of VSMCs from the contractile to the synthetic phenotype. This transformation to the synthetic phenotype is an important step in the formation of the atherosclerotic lesion. METHODS: Cultures were identified as being of smooth muscle origin through staining with the cytoskeletal marker, alpha-smooth muscle actin. Proliferation assays were performed by seeding confluent cultures of passages 4 to 7 into six-well plates at 10,000 cells per well. After serum starvation, samples were incubated with IL-1 beta (1 ng/ml). Cell number was determined on a daily basis. To study extracellular matrix production, cells were propagated in tissue culture chamber slides in the absence or presence of growth media containing IL-1 beta. After fixation with 100% methanol, each sample was stained with a primary antibody specific for an extracellular matrix component. After staining with the fluorescein-tagged secondary antibody, each sample was examined using immunofluorescent microscopic examination. RESULTS: The results of our proliferation assays showed that IL-1 beta caused a significant increase in the proliferation of VSMCs at 24, 48, 72, and 96 hours (p < or = 0.003 when comparing IL-1 beta-treated samples with control specimens at each time period using unpaired t test). The number of IL-1 beta-treated cells at 96 hours was double the number present in the control samples (16,033 +/- 238 vs 8102 +/- 824). When compared with control samples, IL-1 beta was found to affect the production of extracellular matrix proteins by infragenicular VSMCs. IL-1 beta caused an increase in the production of fibronectin, a decrease in the production of laminin, and no change in the production of collagen type IV. CONCLUSIONS: These results suggest that interleukin-1 beta acts as a potent stimulant of the proliferation of human infragenicular VSMCs. IL-1 beta also acts to augment the production of fibronectin by these cells. Fibronectin has been implicated in the phenotypic transformation of VSMCs from the contractile to the synthetic state. Therefore, IL-1 beta may serve as an important regulatory factor in the development of atherosclerosis by stimulating the proliferation of VSMCs and their transformation to the synthetic state, two important steps in the formation of the atherosclerotic lesion.

Insulin-like growth factor-I binding in injury-induced intimal hyperplasia of rabbit aorta.

PURPOSE: The proliferation of arterial-wall smooth muscle cells is an important step in the formation of intimal hyperplasia. Insulin-like growth factor-I (IGF-I) is a mitogen that exerts its effects through specific receptors located on the cell membrane. IGF-I has been found to promote the multiplication of vascular smooth muscle cells in culture. This study aimed to evaluate the status of IGF-I binding in injury-induced intimal hyperplasia in a rabbit model. METHODS: We used binding techniques to study IGF-I binding of control and hyperplastic aortas of adult White New Zealand rabbits. Hyperplasia was induced by balloon-catheter injury. At 2 weeks and 1, 2, 4, and 7 months after injury, segments of abdominal aortas were harvested from two control and six study rabbits, and 20-micrometer-thick frozen sections were obtained. Hematoxylin and eosin-stained sections confirmed the presence of intimal hyperplasia in the hyperplastic aortas. Adjacent sections were incubated in a buffer solution containing 125I-IGF-I in the presence and absence of an excess of unlabeled IGF-I. Autoradiograms were then obtained by apposing the treated sections to autoradiography film, which was developed at 3 days and analyzed by comparison with the hematoxylin and eosin-stained sections under light microscopy. A marked increase in IGF-I binding grain density was observed in the areas corresponding to the hyperplastic lesions. To characterize these binding sites, binding inhibition studies were performed and the dissociation constant (K d) and maximum binding capacity (B max) were obtained from Scatchard analysis. RESULTS: Six hyperplastic aortas for each time interval and a total of nine control aortas were evaluated. The K d of the hyperplastic aortas (1.5+/-0.2 nmol/L) was not significantly different from that of control aortas (1.3+/-0.2 nmol/L), which indicated similar high-affinity IGF-I binding sites in normal and hyperplastic arteries. The results of B max were 6.9+/-1.2, 8.5+/-2.1, 12.4+/-2.1, 20.4+/-5.9, 20.6+/-3.2, and 8.1+/-1.3 pmol/L for control, 2 weeks, 1 month, 2 months, 4 months, and 7 months, respectively. With analysis of variance (p<0.05), B max values at 1, 2, and 4 months were significantly higher than those of control aortas. B max values returned to levels not significantly different from those of control aortas at the 7-month interval. CONCLUSION: Increased IGF-I binding in the hyperplastic aortas suggests that IGF-I plays an important role in the proliferation of arterial wall cellular components during the hyperplastic process.

The protective effect of vein cuffed anastomoses is not mechanical in origin.

PURPOSE: Intimal hyperplasia (IH) is a proliferative process of vascular smooth muscle cells that occurs after an arterial injury, particularly at outflow anastomoses of prosthetic bypass grafts. IH causes stenosis that leads ultimately to graft flow reduction and thrombosis. We have demonstrated previously that vein cuff interposition between an expanded polytetrafluoroethylene (e-PTFE) graft and artery at distal anastomoses diminished IH formation in the arterial outflow as compared with noncuffed anastomoses. Improved long-term patency rates associated with the placement of an interposition vein cuff at the distal anastomosis of e-PTFE grafts to infrageniculate arteries have also been demonstrated clinically. This study examined the mechanical factors that may contribute to the protective effect of cuffed anastomoses. These factors include the expansibility of the vein cuff as compared with e-PTFE, as well as the angle of the cuffed anastomosis. METHODS: Compatible animals were selected by use of platelet aggregation studies. Nine dogs, group A, received a 4 mm e-PTFE graft plus a 1 cm long interposition vein cuff at the distal anastomosis in the left carotid artery. The same procedure was done on the right side, and in addition the vein cuff was encircled by an e-PTFE jacket incorporated into the anastomosis to prevent the expansion of the vein cuff with arterial pulsation. To study the effect of distal anastomotic angle and geometry on the formation of IH, five dogs, group B, received a 4 mm e-PTFE graft in both sides. On the left, the distal anastomosis was performed between the graft and the artery at an acute angle as it is commonly done when a bypass graft is placed. On the right side a 1 cm long, 6 mm diameter e-PTFE segment was interposed between the artery and the graft at a perpendicular angle. This geometry mimicked the right angle of a vein cuff-to-artery anastomosis. After 10 weeks the grafts were harvested, and the thickness of IH was measured with an ocular micrometer under light microscopy. RESULTS: In group A, one dog had bilateral graft thrombosis (12%), and these grafts were discarded. In the remaining eight dogs there was no statistically significant difference in the thickness of IH between the right (jacketed group) and the left side (nonjacketed/control group), showing that vein cuff expansibility did not play a role in protecting against the formation of IH. In group B, bilateral graft thrombosis occurred in four of five dogs (80%), suggesting that the perpendicular anastomotic angle was not protective. CONCLUSION: These results suggested that the protective effect of the vein cuff is not mechanical in origin.

The clinical impact of risk factor analysis and prophylaxis on pulmonary embolism.

Pulmonary emboli cause 50,000 deaths annually despite recognized risk factors and methods of prophylaxis. To determine the impact of risk factor analysis and the use of prophylaxis, a retrospective chart review of patients suffering pulmonary embolism (PE) at Georgetown University Hospital was performed. During a fifty-month period, 25,000 surgical and 36,000 nonsurgical admissions included 171 cases of PE. The incidence of PE among surgical patients was 0.24% (n = 61) and was 0.30% (n = 110) among nonsurgical patients as confirmed in 82% by pulmonary angiography or high-probability ventilation/perfusion scans. PE prophylaxis included pneumatic stockings, low-dose heparin, combination low-dose heparin/stockings, and coumarin. However, prophylactic measures were absent in 23% of the surgical and in all the nonsurgical patients suffering PE. On the basis of established criteria (SVS/ISCVS), 57% of surgical patients suffering PE were considered at high risk as compared with 13% of nonsurgical patients. Conversely, 54% of nonsurgical patients suffering a PE were considered to be at low risk. Standard treatment modalities were instituted after nonfatal PE: anticoagulation (61%), inferior vena cava filter (14%), and anticoagulation/filter (6%). While risk factor analysis identifies high-risk surgical patients, it may be less effective in identifying nonsurgical patients at increased risk for PE.

Vascular stent deployment in vein bypass grafts: observations in an animal model.

BACKGROUND: An important cause of vein graft failure is anastomotic stenosis caused by myointimal hyperplasia. Intravascular stents may allow balloon dilation of these hyperplastic lesions, thereby increasing secondary graft patency. METHODS: To evaluate intravascular stent deployment in vein grafts, we implanted 26 stents across the anastomotic sites of reversed vein grafts in 13 sheep. Stent deployment was evaluated immediately and at 3, 8, and 24 weeks by arteriography, light microscopy, and scanning electron microscopy. In a second animal cohort, stent-arterial wall contact after deployment was evaluated with intravascular ultrasonography (IVUS). Stents were imaged with IVUS after partial (n = 5) and complete (n = 5) expansion in 10 sheep carotid arteries. RESULTS: Stents were deployed across vascular anastomoses without immediate thrombosis. Partial neointimal coverage occurred after 3 and 8 weeks, with complete coverage by 24 weeks. Complications included distal migration (n = 3), arteriographic stenosis (n = 2), and late graft occlusion (n = 2). Incomplete stent-vessel wall contact at deployment was observed in the stents with complications. IVUS accurately showed stent expansion and the degree of stent-vessel wall contact. CONCLUSIONS: Stents can be deployed in vein grafts with the expectation of neointimal coverage and maintenance of graft patency. IVUS may prove important in guiding optimal stent deployment by providing an assessment of stent-vessel wall contact.

Autoradiographic mapping and characterization of insulin-like growth factor-I receptor binding in human greater saphenous vein.

PURPOSE: The proliferation of vascular smooth muscle cells is an important step in the process of intimal hyperplasia. Veins exposed to arterial pressure develop intimal hyperplastic lesions that lead to failure of vein bypasses. Insulin-like growth factor-I is a polypeptide hormone structurally related to insulin with insulin-like metabolic effects. Insulin-like growth factor-I has been found to work in concert with other growth factors, including platelet-derived growth factor, to promote the growth of vascular smooth muscle cells in culture. Insulin-like growth factor-I exerts its effects via specific receptors located on the cell surface. We studied the in situ distribution of insulin-like growth factor-I receptor binding using autoradiography and examined insulin-like growth factor-I binding characteristics in normal human greater saphenous vein. METHODS: Frozen sections 20 microns thick were prepared from the greater saphenous vein specimens. The sections were incubated in a buffer containing 125I-insulin-like growth factor-I in the presence of increasing concentrations of the unlabeled peptide. Autoradiograms were obtained by apposing the treated sections to autoradiography film. RESULTS: Analysis of the autoradiographs showed that insulin-like growth factor-I binding was consistently present in the wall of human greater saphenous vein. To characterize these binding sites binding inhibition studies were performed. High-affinity insulin-like growth factor-I receptor binding was found with dissociation constant of 1.0 +/- 0.32 nmol/L and maximum binding capacity of 0.46 +/- 0.23 pmol/mg protein. These values are consistent with a physiologic role for insulin-like growth factor-I in the tissue examined. CONCLUSIONS: The presence of high-affinity (dissociation constant = 1.0 +/- 0.32) insulin-like growth factor-I binding sites in the wall of saphenous vein suggests that insulin-like growth factor-I plays an important role in regulating the proliferation of venous wall cellular components, an essential step in the process of venous intimal hyperplasia.