Endovascular stenting of nonmalignant superior vena cava syndrome.

Superior vena cava (SVC) syndrome is associated with advanced malignancy of the chest. Extensive experience is published in the literature regarding the use of endovascular intervention for symptomatic relief in these individuals with limited survival. Symptomatic SVC obstruction may occur from benign conditions that may not alter life expectancy. There are few data regarding endovascular therapy in this setting. We retrospectively analyzed our experience using endovascular intervention for benign SVC obstruction in 19 patients. In our series, the mean age was 46.4 years; 58% were female and 14/19 cases were due to an intravascular device. All patients experienced symptomatic relief. Median follow-up was 28.8 months. Three patients required secondary procedures to maintain patency. Four patients had procedural complications, which did not affect the outcomes. One patient died from complications of anticoagulation at 24 months. Endovascular procedures aimed at relieving SVC stenosis seem to be effective in patients with benign disease.

Efficacy and durability of autogenous saphenous vein conduits for lower extremity arterial reconstructions in preadolescent children.

OBJECTIVE: Limb length discrepancies (LLDs) in growing children may accompany extremity arterial occlusions. Revascularization with vein grafts has been questioned because of degenerative graft changes observed at other sites. This study was undertaken to define vein graft durability and efficacy in lower extremity revascularizations in preadolescent children. STUDY DESIGN: Fourteen children (10 boys, 4 girls) with a mean age of 7.3 years (range, 2-11 years) who underwent 16 lower extremity revascularizations with greater saphenous vein grafts were subjected to follow-up with graft ultrasonography, ankle/brachial indices (ABIs) with and without exercise, and limb length determinations. A mean of 5.7 years elapsed between the onset of ischemia and operation. Arterial occlusions resulted from cardiac catheterizations (11), arteritis (1), dialysis cannulation (1), and penetrating trauma (1). Indications for operation included LLD (6), claudication (4), both LLD and claudication (3), markedly diminished ABIs with a potential for LLD (2), and a traumatic transection with hemorrhage (1). The reconstructions with 15 reversed and one in situ vein grafts included iliofemoral (11), femorofemoral (1), aortofemoral (1), femoropopliteal (1), popliteal-popliteal (1), and popliteal-posterior tibial (1) arterial bypass grafts. RESULTS: Among patent grafts available for follow-up, 36% (5 of 14) remained unchanged, 50% (7 of 14) developed nonaneurysmal dilatation, and 14% (2 of 14) exhibited nonprogressive aneurysmal expansion. One graft became occluded, and one graft was lost to follow-up. Collectively, the grafts manifest an 11.2% expansion at an average of 10.7 years postoperatively. ABIs increased from 0.75 preoperatively to 0.97, at an average of 11.0 years postoperatively. LLDs were reduced from 1.66 to 1.24 cm, at an average of 11.4 years postoperatively. CONCLUSION: Vein graft reconstructions of lower extremity arteries in preadolescent children are durable. They provide an efficacious means of restoring normal blood flow, and in 70% of children their preexisting LLDs were reduced.

Impact of changes in transportation and commuting behaviors during the 1996 Summer Olympic Games in Atlanta on air quality and childhood asthma.

CONTEXT: Vehicle exhaust is a major source of ozone and other air pollutants. Although high ground-level ozone pollution is associated with transient increases in asthma morbidity, the impact of citywide transportation changes on air quality and childhood asthma has not been studied. The alternative transportation strategy implemented during the 1996 Summer Olympic Games in Atlanta, Ga, provided such an opportunity. OBJECTIVE: To describe traffic changes in Atlanta, Ga, during the 1996 Summer Olympic Games and concomitant changes in air quality and childhood asthma events. DESIGN: Ecological study comparing the 17 days of the Olympic Games (July 19-August 4, 1996) to a baseline period consisting of the 4 weeks before and 4 weeks after the Olympic Games. SETTING AND SUBJECTS: Children aged 1 to 16 years who resided in the 5 central counties of metropolitan Atlanta and whose data were captured in 1 of 4 databases. MAIN OUTCOME MEASURES: Citywide acute care visits and hospitalizations for asthma (asthma events) and nonasthma events, concentrations of major air pollutants, meteorological variables, and traffic counts. RESULTS: During the Olympic Games, the number of asthma acute care events decreased 41.6% (4.23 vs 2.47 daily events) in the Georgia Medicaid claims file, 44.1% (1.36 vs 0.76 daily events) in a health maintenance organization database, 11.1% (4.77 vs 4.24 daily events) in 2 pediatric emergency departments, and 19.1% (2.04 vs 1.65 daily hospitalizations) in the Georgia Hospital Discharge Database. The number of nonasthma acute care events in the 4 databases changed -3.1%, +1.3%, -2.1%, and +1.0%, respectively. In multivariate regression analysis, only the reduction in asthma events recorded in the Medicaid database was significant (relative risk, 0.48; 95% confidence interval, 0.44-0.86). Peak daily ozone concentrations decreased 27.9%, from 81.3 ppb during the baseline period to 58.6 ppb during the Olympic Games (P<.001). Peak weekday morning traffic counts dropped 22.5% (P<.001). Traffic counts were significantly correlated with that day's peak ozone concentration (average r = 0.36 for all 4 roads examined). Meteorological conditions during the Olympic Games did not differ substantially from the baseline period. CONCLUSIONS: Efforts to reduce downtown traffic congestion in Atlanta during the Olympic Games resulted in decreased traffic density, especially during the critical morning period. This was associated with a prolonged reduction in ozone pollution and significantly lower rates of childhood asthma events. These data provide support for efforts to reduce air pollution and improve health via reductions in motor vehicle traffic.

Impact of chronic obstructive pulmonary disease on elective and emergency abdominal aortic aneurysm repair.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with abdominal aortic aneurysm (AAA) expansion and is considered by some to be a relative contraindication to conventional aortic surgery. This study was undertaken to determine if COPD increases operative death, morbidity, intensive care unit (ICU) length of stay (LOS), and hospital LOS, after AAA repair. METHODS: Data from national administrative records supplemented with laboratory data previously obtained for a system-wide study were analyzed in a retrospective review of 1053 consecutive patients (264 with and 789 without COPD) undergoing operation for intact or ruptured AAAs in Veterans Administration Hospitals from 1997 to 1998. Bivariate comparisons and multivariate regression were used to evaluate the impact of COPD on the number of days of ventilation, ICU LOS, total hospital LOS, and death, while controlling for other known risk factors, including acute myocardial infarction, renal failure, and age. RESULTS: The mortality rate in elective aneurysm patients did not differ (P =.99) between patients with (3.7%) or without COPD (3.7%). However, elective AAA repair was associated with longer hospital LOS (14.4 vs 12.3 days, P =.01), longer ICU LOS (6.5 vs 5.4 days, P =.01), and a higher incidence of requiring 96 hours or more ventilation (6.9% vs 3.6%, P =.02) in patients with COPD. Ruptured AAA affected 4.9% of patients and was strongly associated with COPD (P =.02); however, COPD did not result in a statistically significant increase in death (P =.25). CONCLUSIONS: Although COPD does not appear to increase operative death, it is associated with an increased risk of rupture. Elective repair of AAA should not be deferred in patients with COPD despite their higher LOSs and need for postoperative ventilation.

Regional differences in phorbol 12-myristate 13-acetate stimulation of PDGF production in the normal canine aorta.

OBJECTIVE: Platelet-derived growth factor (PDGF) is a potent smooth muscle cell mitogen implicated in the development of intimal hyperplasia and atherosclerosis. A regional variation in canine aortic production of PDGF (greater in the distal than in the proximal aorta) was demonstrated previously in organ culture. The response of aortic segments in organ culture, as well as of aortic endothelial cells and smooth muscle cells, to stimulators of PDGF secretion-phorbol 12-myristate 13-acetate (PMA) and thrombin-was assessed to elucidate whether these regional variations were due to intrinsic differences in the abilities of cells to produce PDGF. METHODS: Proximal and distal aortic segments were removed from 10 dogs and placed in organ culture, then treated with PMA or thrombin for 72 hours. PDGF in the conditioned media was measured by radioreceptor assay. RESULTS: PDGF production in the distal, unstimulated aorta was 2.5-fold higher than that in the proximal aorta (P <.05). Treatment of the proximal aorta with 10 nmol/L and 100 nmol/L PMA increased PDGF production twofold and threefold, respectively, whereas no increase with PMA treatment was seen in the distal aorta. After thrombin treatment, no increase in PDGF production was noted in the proximal aorta and only a minimal increase was noted in the distal aorta. Endothelial cells and smooth muscle cells (n = 6) were cultured from four aortic segments (ascending thoracic, descending thoracic, abdominal, and infrarenal) and treated with PMA. PDGF production by unstimulated endothelial cells from the infrarenal aorta was 2.5-fold higher (P <.01) than that from the ascending thoracic aorta. With PMA treatment, PDGF secretion increased in endothelial cells from all segments, the greatest percentage increase being observed in the proximal segments. Thrombin also increased PDGF release from endothelial cells, but with no regional variation. Unstimulated smooth muscle cells did not exhibit regional variation in PDGF production and did not increase PDGF secretion after treatment with PMA or thrombin. CONCLUSIONS: These findings suggest that endothelial cells in the aorta may have a differential capacity to produce PDGF in response to stimulants, reflecting intrinsic differences in endothelial cells from the proximal aorta versus the distal aorta, and this may account in part for the propensity of the distal aorta to develop atherosclerosis.

Further evidence for genetic heterogeneity in familial hemophagocytic lymphohistiocytosis (FHLH).

Familial hemophagocytic lymphohistiocytosis (FHLH; MIM #267700) is an autosomal recessive disorder of immune regulation characterized by fever, hepatosplenomegaly, and cytopenia that is fatal without bone marrow transplantation. Recent studies have suggested the existence of FHLH loci at 9q21.3-22 and t0q21-22 in Asian and European/African/Australian families, respectively. We studied two unrelated Canadian families in which first cousins were affected with FHLH. In an effort to localize the causative gene, we completed a genome-wide screen for homozygosity by descent by using an automated system to genotype 400 highly polymorphic dinucleotide repeat markers covering the genome with an average resolution of 10 centiMorgans (cM). We identified a total of three candidate loci that met the combined criteria for homozygosity by descent in one family and shared maternal alleles in the other family. One of these, D9S1690, had a cytogenetic localization (9q22.33) proximal to a previously reported inversion of chromosome 9 in an FHLH patient. However, additional closely linked flanking markers within 1-2 cM of all three candidates did not conform to the criteria for linkage in either family. Similarly, we excluded the linked 9q21.3-q22 and 10q21-22 regions recently reported in Asian and European/African/Australian families, respectively. The two families were then analyzed independently to encompass the possibility that they were segregating separate genes. Six additional candidate loci were identified on the basis of homozygosity for the same allele in all affected members of one family, but further analysis of closely linked flanking markers did not demonstrate similar homozygosity. Our data provide further evidence of genetic heterogeneity in FHLH and suggest the existence of at least a third locus for this disease.

The migratory response to platelet-derived growth factor of smooth muscle cells isolated from synthetic vascular grafts in a canine model.

OBJECTIVE: Previous studies on smooth muscle cells (SMCs) harvested from implanted synthetic grafts demonstrate increased production of platelet-derived growth factor (PDGF) but decreased proliferative response compared with aortic SMCs. The purpose of this study was to determine the migratory response of graft versus aortic SMCs. METHODS: Thoracoabdominal grafts were implanted in beagles. The SMCs were harvested from the graft and infrarenal aorta. Migration was determined with the use of a razor-scrape assay and computerized image analysis. RESULTS: The mean distance migrated and the number of cells that migrated were greater in graft SMCs at baseline (185 +/- 18 micrometer and 108 +/- 17 cells) compared with aortic cells (110 +/- 10 micrometer and 42 +/- 5 cells)(P <.05). Baseline differences persisted after treatment with antibodies to PDGF. The addition of PDGF (10 ng/mL) resulted in increased migration in both graft (229 +/- 23 micrometer and 146 +/- 20 cells) and aortic SMCs (130 +/- 9 micrometer and 70 +/- 5 cells) compared with baseline (P <.05). The relative increase in response to PDGF was similar between the two groups (P = not significant). CONCLUSIONS: Graft SMCs differ phenotypically from aortic SMCs; they exhibit increased basal migration that is independent of autocrine stimulation by PDGF. In contrast to their blunted proliferative response, graft SMCs have a similar migratory response to PDGF compared with aortic SMCs.

Mechanism of dacron-activated monocytic cell oxidation of low density lipoprotein.

PURPOSE: Oxidized lipids are believed to contribute to atherogenesis and may play a role in the development of anastomotic intimal hyperplasia in prosthetic vascular grafts. This study examines the hypothesis that clinically relevant graft material activates monocytes to oxidize low density lipoprotein (LDL). METHODS: LDL and Dacron or expanded polytetrafluoroethylene (ePTFE) graft material were incubated in the presence of U937 cells, a monocytic cell line. LDL oxidation was measured by conjugated dienes, lipid peroxides, thiobarbituric acid-reacting substances, and electrophoretic mobility. Cell production of superoxide was measured by ferricytochrome c reduction. Metal ion requirement was assessed with the metal chelators, ethylenediaminetetra-acidic acid, deferoxamine, and bathocuproinedisulfonic acid. To determine whether human monocytes were capable of being activated by Dacron graft material to oxidize LDL, freshly isolated peripheral blood monocytes were also studied. RESULTS: Incubation of LDL with U937 cells and Dacron increased LDL oxidation by 5- to 20-fold. LDL incubated with ePTFE or U937 cells alone resulted in minimal oxidation. Dacron graft increased U937 cell production of superoxide by 4-fold, whereas ePTFE had no effect. Superoxide dismutase inhibited Dacron-activated U937 cell oxidation of LDL by greater than 50%, which indicates a role for superoxide. Ethylenediaminetetra-acidic acid, deferoxamine, and bathocuproinedisulfonic acid each inhibited Dacron-activated U937 cell oxidation of LDL. Human peripheral blood monocytes were activated by Dacron graft material to oxidize LDL; superoxide dismutase inhibited Dacron-activated human monocytic oxidation of LDL, which suggests a role for superoxide. CONCLUSION: These results suggest that Dacron graft material activates monocytes to oxidize LDL by a mechanism that involves superoxide and requires iron and copper ions. Our work suggests a mechanism by which lipids that have been deposited within implanted vascular grafts may become oxidized. Oxidized lipids may contribute to the cellular dysfunction that results in anastomotic intimal hyperplasia and graft failure.

The proliferative response to platelet-derived growth factor of smooth muscle cells isolated from synthetic vascular grafts in a canine model.

OBJECTIVE: Previous studies on graft healing have shown increased platelet-derived growth factor (PDGF) production in graft segments versus native aortic segments. The purpose of this study was to characterize the proliferative response of graft smooth muscle cells (SMCs) to PDGF. METHODS: Thoracoabdominal grafts were implanted in beagles. SMCs were harvested from the graft and the proximal and distal aortas. Basal proliferation was assessed with growth curves in primary culture. The proliferative response to PDGF then was compared with [3H]thymidine uptake studies and cell counts. Finally, PDGF receptors were characterized with radio-labeled ligand binding assays. RESULTS: The growth curves showed that the graft SMCs entered log-phase growth 2 days earlier than did the aortic SMCs. Stimulation of quiescent early-passage graft SMCs with PDGF (10 ng/mL) resulted in a 1.7 +/- 0.1-fold increase in [3H]thymidine incorporation, which was significantly less than that of the SMCs from both the proximal aorta (11.8 +/- 3.0) and the distal aorta (10. 2 +/- 1.9; P <.5). Similarly, the 1.1 +/- 0.1-fold increase in graft SMC cell number was significantly less than the increases for both proximal (2.8 +/- 0.5) and distal (2.9 +/- 0.8) aortic SMCs (P <.5). Binding studies on quiescent first-passage cells showed fewer PDGF receptors available for binding in the graft SMCs (185 +/- 70 fmol/million cells) as compared with both the proximal (419 +/- 147 fmol/million cells) and the distal (387 +/- 112 fmol/million cells) aortas (P <.5). Binding affinity was similar for the three groups. CONCLUSION: Graft SMCs exist in a chronic proliferative state but exhibit a decreased proliferative response to PDGF and have fewer receptors available for binding PDGF than do aortic SMCs in vitro.

Relationship of age, gender, race, and body size to infrarenal aortic diameter. The Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Investigators.

PURPOSE: To assess the effects of age, gender, race, and body size on infrarenal aortic diameter (IAD) and to determine expected values for IAD on the basis of these factors. METHODS: Veterans aged 50 to 79 years at 15 Department of Veterans Affairs medical centers were invited to undergo ultrasound measurement of IAD and complete a pre-screening questionnaire. We report here on 69,905 subjects who had no previous history of abdominal aortic aneurysm (AAA) and no ultrasound evidence of AAA (defined as IAD > or = 3.0 cm). RESULTS: Although age, gender, black race, height, weight, body mass index, and body surface area were associated with IAD by multivariate linear regression (all p < 0.001), the effects were small. Female sex was associated with a 0.14 cm reduction in IAD and black race with a 0.01 cm increase in IAD. A 0.1 cm change in IAD was associated with large changes in the independent variables: 29 years in age, 19 cm or 40 cm in height, 35 kg in weight, 11 kg/m2 in body mass index, and 0.35 m2 in body surface area. Nearly all height-weight groups were within 0.1 cm of the gender means, and the unadjusted gender means differed by only 0.23 cm. The variation among medical centers had more influence on IAD than did the combination of age, gender, race, and body size. CONCLUSIONS: Age, gender, race, and body size have statistically significant but small effects on IAD. Use of these parameters to define AAA may not offer sufficient advantage over simpler definitions (such as an IAD > or = 3.0 cm) to be warranted.

Coronary bypass in vascular patients: a relatively high-risk procedure.

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.

Platelet-derived growth factor production by cells from Dacron grafts implanted in a canine model.

PURPOSE: Previous studies of grafts implanted in dogs documented a time-dependent increase in platelet-derived growth factor (PDGF) production that correlated with inner-capsule thickness. The purpose of this study was to identify the cells in vascular grafts that produce PDGF. METHODS: Dacron thoracoabdominal grafts were seeded with autologous endothelial cells (ECs), implanted in 11 beagles, and removed after 4 or 20 weeks. ECs and smooth muscle cells (SMCs) were cultured from grafts and adjacent aorta, and PDGF in the conditioned media was measured by radioreceptor assay. The PDGF A-chain mRNA level in freshly harvested cells was assessed using reverse transcriptase, followed by polymerase chain reaction, and expressed as a ratio of glyceraldehyde-3-phosphate dehydrogenase signal. Localization of PDGF A-chain and B-chain protein was also examined with immunohistochemical analysis. RESULTS: Graft and aortic ECs in primary culture did not produce significantly different amounts of PDGF in 72 hours, averaging 368 +/- 160 and 340 +/- 81 pg/microgram DNA, respectively. Graft SMCs in primary culture produced significantly more PDGF than aortic SMCs (584 +/- 343 and 113 +/- 94 pg/microgram DNA, respectively; p < 0.01). Graft SMC PDGF secretion remained greater than aortic SMC PDGF secretion through at least six cell passages. PDGF A-chain mRNA levels were not significantly different for aortic or graft ECs. The PDGF A-chain mRNA level was significantly higher for graft SMCs than aortic SMCs (2.44 +/- 0.67 and 1.45 +/- 0.57 pg/microgram, respectively; p < 0.03). Immunocytochemical analysis detected PDGF A-chain and B-chain protein in the ECs from both native aorta and graft as well as the subendothelial SMCs in the graft, but not in the SMCs of the native aorta. CONCLUSIONS: These results suggest that graft SMCs are functionally altered, producing more PDGF than aortic SMCs. PDGF produced by graft SMCs may contribute to the development of intimal hyperplasia.

Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb.

PURPOSE: Smooth muscle cell (SMC) migration and proliferation are prominent features of intimal hyperplasia. Previous studies have shown that inhibition of c-myb inhibits arterial SMC proliferation. Our goal was to evaluate the effect of an antisense oligonucleotide targeted to c-myb on the proliferation and migration of SMC explanted from synthetic vascular grafts. METHODS: SMCs were enzymatically removed from aortas and Dacron grafts explanted from dogs (n = 5). For proliferation studies, quiescent SMCs were incubated with either 0.0, 0.5, 5.0, or 10.0 microM antisense (GTGTCGGGGTCTCCGGGC) or sense (GCCCGGAGACCCCGACAC) oligonucleotides to c-myb. Proliferation was measured after 24 hours by incorporation of [3H]thymidine. Migration was assessed 24 hours after a razor injury. RESULTS: Antisense to c-myb consistently inhibited proliferation and migration of both native aortic and graft SMCs in a dose-dependent fashion. At a concentration of 10 microM antisense oligonucleotide, aortic and graft SMC proliferation rates were 32% +/- 20% and 56% +/- 9% of control samples, respectively. At 25 microM antisense, the number of migrating aortic and graft SMCs decreased to 41.9% +/- 26.8% and 51.9% +/- 34.1% of control samples, respectively. CONCLUSIONS: Our results suggest that antisense oligonucleotides to c-myb may be useful in the inhibition of SMC proliferation and migration associated with development of intimal hyperplasia.

Regional differences in platelet-derived growth factor production by the canine aorta.

Platelet-derived growth factor (PDGF) is a potent mitogen and chemotactic agent which may be involved in the formation of proliferative lesions of the arterial system, such as intimal hyperplasia and atherosclerosis. To examine the regional variation in vessel wall production of this mitogen, PDGF production and PDGF A chain mRNA expression by normal arterial wall was studied as a function of vessel location. PDGF production by canine aortic segments was measured after 72 h in organ culture, revealing significantly more PDGF produced by the distal compared to proximal aorta at 77 +/- 10 versus 14 +/- 6 pg/cm2/72 h (p<0.05). Endothelial cells (EC) and smooth muscle cells (SMC), isolated from analogous aortic sites, were grown in tissue culture and the conditioned medium was assayed for PDGF. EC in vitro demonstrated a similar geographic trend in PDGF production (distal=1,501 +/- 389 pg/microgram DNA/72 h, proximal=759 +/- 230 pg/microgram DNA/72 h; p=0.17). PDGF production by SMC in cell culture had a similar pattern with cells from the distal aorta producing 58 +/- 28 pg PDGF/microgram DNA/72 h, compared to cells from the proximal aorta producing 37 +/- 15 pg PDGF/microgram DNA/72 h (p=0.13). Freshly harvested EC and SMC, isolated from the same aortic sites, were subjected to quantitation of PDGF mRNA levels using a coupled reverse transcriptase and polymerase chain reaction amplification method, with glyceraldehyde-phosphate dehydrogenase (GAPDH) as a control. The ratio of PDGF A chain:GAPDH mRNA was significantly greater in distal aortic SMC, 2.30 +/- 0.99, compared to proximal aortic SMC, 1.27 +/- 0.46 (p=0.05), but was not significantly different between proximal and distal aortic EC (p=0.86). These findings demonstrate significant regional differences in PDGF production in the normal canine aorta. Additionally, SMC are implicated as a significant contributor to the regional variation in PDGF production.

Graft smooth muscle cells specifically synthesize increased collagen.

PURPOSE: Anastomotic intimal hyperplasia is characterized by smooth muscle cell (SMC) proliferation, but its final form is predominantly extracellular matrix. The purpose of this study was to compare collagen synthesis from graft SMC to that from adjacent native arterial SMC. METHODS: Thoracoabdominal bypass grafts were excised 20 weeks after implantation into canine models. SMC harvested from six anastomotic graft segments and adjacent native aorta were passaged twice, grown to near-confluence, and then assayed for collagen synthesis and total protein synthesis. In four of these sites type I alpha-1 procollagen mRNA levels were measured and normalized to glyceraldehyde-3-phosphate dehydrogenase. To control for increases in collagen synthesis associated with proliferation, SMC were plated at equal densities and tritium-thymidine incorporation and DNA concentration were determined. Data (mean +/- SE) were analyzed with two-factor ANOVA for repeated measures and paired Student t test and were considered significant if p < 0.05. RESULTS: There was no difference in thymidine incorporation and total protein synthesis between groups, but collagen synthesis (graft: 52.9 +/- 1.6 disintegrations per minute/ng DNA versus native: 42.6 +/- 1.9 dpm/ng DNA; p = 0.03) and collagen synthesis as a percentage of total protein synthesis (graft: 7.16% +/- 0.11% versus native: 5.8% +/- 0.14%; p = 0.001) increased significantly in graft SMC as compared to native SMC. Type I alpha-1 procollagen mRNA levels were higher in graft SMC, but this difference was not significant. CONCLUSIONS: Graft SMC specifically produce more collagen than SMC from adjacent native artery. This change does not simply reflect increases in either total protein synthesis or proliferation and may, in part, be due to increased collagen gene expression.

Differential monocytic cell adherence to specific anatomic regions of the canine aorta.

Circulating monocytes and vascular endothelial cells (EC) interact in a complex and dynamic manner that varies between vascular beds. The objective of this study was twofold: to ascertain if monocytic cell adhesion to vascular endothelium differed between specific anatomic regions of the canine aorta, and to investigate the effect of known EC stimulators on monocytic cell adhesion to cells from these regions. Initial in vitro studies measuring adherence of U937 cells, a human monocytic cell line, to canine jugular vein and aortic EC monolayers revealed a dose-dependent increase in adhesion to EC stimulated with interleukin-1 (IL-1), lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), or thrombin. While there was no regional difference in monocytic cell adherence to unstimulated EC in tissue culture, studies demonstrated greater monocytic cell adhesion to stimulated EC cultured from the distal versus proximal aorta. In organ culture, unstimulated adhesion of U937 cells or autologous monocytes was significantly greater to the distal aorta than the proximal aorta. Although monocytic cell adhesion to both the proximal and distal aorta increased with stimulation, the percentage increase in the proximal aorta, 1,086% with IL-1, 237% with PMA, 209% with LPS, and 174% with thrombin, was greater than in the distal aorta, demonstrating a significant functional difference in the endothelium from separate anatomic regions of a single vessel. This may have a direct relevance to the regional specificity of vascular disease.

Increased platelet-derived growth factor production and intimal thickening during healing of Dacron grafts in a canine model.

PURPOSE: Growth factor production by endothelial cells on grafts may play a role in the development of intimal hyperplasia and subsequent graft failure. METHODS: To study the relationship between platelet-derived growth factor production and graft healing, 26 beagles underwent placement of 20 cm long, 6 mm internal diameter, knitted Dacron thoracoabdominal grafts, either seeded with autologous endothelial cells (n = 14) or unseeded controls (n = 12). The grafts and adjacent arteries were removed 4 or 20 weeks after implantation for measurement of platelet-derived growth factor production in organ culture, endothelial cell coverage, and intimal thickness. RESULTS: Midgraft platelet-derived growth factor production by seeded graft segments increased from 41 +/- 6 to 148 +/- 27 pg/cm2/72 hr (p < 0.002) between 4 and 20 weeks. This was accompanied by a significant increase in inner-capsule thickness. Platelet-derived growth factor production by control graft segments also increased from 58 +/- 21 to 163 +/- 42 pg (p < 0.05) and was similar to that of seeded grafts despite more rapid endothelialization of seeded grafts. The increase in growth factor production by Dacron grafts was greater than that of the expanded polytetrafluoroethylene grafts studied previously despite similar endothelial cell coverage. CONCLUSION: This increase corresponded with the rapid appearance of smooth muscle cells in the pseudointima of Dacron grafts, suggesting that these cells may be responsible for the observed increase in platelet-derived growth factor production.

Elevated platelet-derived growth factor production by aortic grafts implanted on a long-term basis in a canine model.

An endothelial cell lining in a prosthetic vascular graft has been shown to decrease graft thrombogenicity. However, previous studies in our laboratory demonstrated that grafts seeded with endothelial cells produced platelet-derived growth factor, a potent smooth muscle cell mitogen that may promote intimal hyperplasia. This study was undertaken to assess temporal changes in platelet-derived growth factor production by grafts seeded with endothelial cells and unseeded grafts and adjacent arteries. Adult beagles underwent placement of 20 to 22 cm long, 8 mm inner diameter, expanded polytetrafluoroethylene thoracoabdominal aortic grafts that were either seeded with autologous jugular vein endothelial cells or were unseeded controls. Grafts and adjacent arteries were removed at times up to 2 years after implantation. The tissue was studied in organ culture and platelet-derived growth factor production was measured after 72 hours with use of a radioreceptor assay. Platelet-derived growth factor production by endothelialized grafts increased significantly over the period studied, especially at the anastomoses, whereas that by arterial segments did not change significantly. The increase in platelet-derived growth factor production was greater in the distal than the proximal anastomotic segment suggesting a possible explanation for the clinical finding of more severe intimal hyperplasia at the distal anastomosis.