Cytokine pattern in aneurysmal and occlusive disease of the aorta.

BACKGROUND: Prominent inflammatory infiltrates of macrophages and T-lymphocytes are found in both aortic occlusive disease (AOD) and abdominal aortic aneurysms (AAA). These cells secrete different cytokines that might affect matrix turnover through modulation of matrix metalloproteinase expression. A different cytokine pattern might account for the evolution of AOD vs AAA. MATERIALS AND METHODS: Six different cytokines were examined to determine whether AOD and AAA could be characterized by unique cytokine patterns. AOD (n = 8) and AAA (n = 8) tissues were collected and serially treated with salt, dimethyl sulfoxide, and urea buffers to extract the soluble matrix or cell-bound cytokines. Levels of IL-1 beta, TNF-alpha, IL-10, IL-12, and IFN-gamma were measured by immunoenzymatic methods. Additionally, RNA levels of IL-12 and IFN-gamma were measured. RESULTS: AAA tissue contained higher levels of IL-10 compared to AOD tissue (P < 0.05). Higher levels of the proinflammatory cytokines IL-1 beta, TNF-alpha, and IL-6 were found in AOD (P < 0.05). mRNA levels of IL-12 and IFN-gamma did not differ between the diseases. Aortic tissues contained large amounts of matrix or cell-bound cytokines. CONCLUSIONS: AAA is characterized by greater levels of IL-10 while IL-1 beta, TNF-alpha, and IL-6 are higher in AOD. Targeted deletion of these cytokines in animal models might help in identifying their role in the progression of AAA.

Tibial bypass using complex autologous conduit: patency and limb salvage.

Over an 8-year period, we performed 93 lower extremity bypasses using complex autologous conduits, which included (1) contralateral greater saphenous vein (GSV), (2) composite GSV, (3) superficial femoral vein, (4) lesser saphenous vein, (5) cephalic or basilic veins, and (6) composite-sequential (PTFE and vein) grafts. These grafts represented 16% of all infrainguinal bypasses during this period, and all grafts were performed to treat limb-threatening ischemia. Survival, patency, and limb salvage were examined by the life-table method. Primary graft patency was 46 and 38% at 3 and 5 years. Assisted-primary patency was 62 and 59%, and secondary graft patency rates were 68 and 64% at 3 and 5 years. Twenty-nine bypasses (31%) required revision to restore or maintain patency. The 3-year limb salvage rate was significantly better when revision was performed for graft stenosis than for graft thrombosis (90% vs. 46%, p < 0.05). Overall limb salvage rate was 73% at 5 years. The mortality rate was 5.4% and the 5-year survival was 51%. Complex autologous tibial bypasses provided acceptable long-term limb salvage in patients with severe ischemia and inadequate ipsilateral GSV. The increased operating time and complexity required did not produce prohibitive operative risks. Postoperative graft surveillance in these complex vein bypasses allowed revision in many cases before graft occlusion occurred and significantly improved long-term limb salvage.

Duplex ultrasound insertion of inferior vena cava filters in multitrauma patients.

BACKGROUND: Techniques for placement of inferior vena cava (IVC) filters have undergone continued evolution from open surgical exposure of the venous insertion site to percutaneous insertion in most cases today. However, the required transport either to an operating room or interventional suite can be complex and potentially hazardous for the multiply injured trauma patient who may require ventilator support, controlled intravenous infusions, or skeletal immobilization. Increased experience with color-flow duplex scanning for routine IVC imaging and portability of ultrasound equipment have suggested the usefulness of duplex-guided IVC filter insertion (DGFI) in critically ill trauma and intensive care unit (ICU) patients. METHODS: A total of 25 multitrauma/ICU patients were considered for DGIF. Screening color-flow duplex scans were performed on all patients, and obesity or bowel gas prevented ultrasound imaging in 2 cases, leaving 23 patients suitable for DGFI. In each case, the IVC was imaged in the transverse and longitudinal planes. The right renal artery was identified as it passed posterior to the IVC and was used as a landmark of the infrarenal segment of the IVC. All procedures were performed at the bedside in a monitored ICU setting using percutaneous placement of titanium Greenfield filters. Duplex scanning after insertion was used to document proper placement, and circumferential engagement of the filter struts in the IVC wall. An abdominal radiograph was also obtained in each case to confirm proper filter location. Duplex ultrasound imaging was repeated within 1 week of insertion to assess IVC and insertion site patency. RESULTS: DGFI was successful in all cases. The filter was deployed at a suprarenal level in one case, as was recognized at the time of postprocedural scanning. Three patients died as a result of their injuries but there were no pulmonary embolism deaths. Repeat duplex scanning was obtained in 17 patients, and revealed no case of IVC or insertion site thrombosis. CONCLUSIONS: Vena caval interruption can be safely performed under ultrasound guidance in a monitored, ICU environment. In selected multiply injured trauma patients, this will reduce the risk, complexity and cost of transport for these critically ill patients. DGFI also reduces procedural costs compared with an operating room or interventional suite, and eliminates intravenous contrast exposure. Preprocedural scanning is essential to identify patients suitable for DGFI, and careful attention must be paid to the known ultrasonographic anatomical landmarks.

Hospital-wide educational program decreases red blood cell transfusions.

BACKGROUND: Because of the numerous risks associated with the use of packed red blood cells (RBCs), it is critical that they be transfused only when appropriate. A hospital-wide educational program was developed in an attempt to improve the transfusion practices and provide a framework for blood bank audit at a Veterans Affairs teaching hospital. MATERIALS AND METHODS: The program required physicians to fill out an information sheet that listed appropriate criteria for transfusion. Charts were reviewed to determine if the transfusion met these criteria. If the transfusion was deemed inappropriate by peer review, the staff physician was notified by letter. The information sheet was used on a voluntary basis without chart review in 1989 and on a mandatory basis beginning in 1990. Transfusion rates and mortality were adjusted to patient days of hospitalization and evaluated using chi 2 analysis. RESULTS: While voluntary use did not affect transfusion rate, mandatory implementation resulted in a 26% decline (P < 0.001) between 1989 and 1990 in the number of RBC units transfused per patient days of hospitalization. A diminished use of RBCs persisted in the subsequent years. There was no increase in mortality during this time to suggest a detrimental effect from the decrease in RBC transfusion. No apparent variation in the hospital population could account for the changes. CONCLUSION: Use of a unique and simple transfusion request sheet as an educational tool resulted in improved transfusion practices at a Veteran Affairs teaching hospital.

Macrophage products inhibit human aortic smooth muscle cell proliferation and alter 1 alpha (I) procollagen expression.

While the role of the foam cell in early atherogenesis has been well characterized, much less is known about the interaction between infiltrating macrophages and medial smooth muscle cells (SMC) in chronic atherosclerosis. Our purpose was to determine the effects of soluble macrophage mediators on normal human aortic SMC proliferation and matrix expression. Human aortic SMC in subconfluent culture were exposed to supernatants from activated lipopolysaccharide (LPS) and nonactivated macrophages. SMC proliferation and type-I procollagen expression were determined. Both activated and nonactivated macrophage supernatants exhibited a potent growth inhibitory effect which became apparent at 48 hours. While nonactivated macrophage supernatant had no effect on procollagen expression, activated supernatant inhibited its expression. (33%; p < 0.05) These findings are consistent with the loss of medial SMC and matrix proteins associated with chronic atherosclerosis.

Platelet-derived growth factor is a cofactor in the induction of 1 alpha(I) procollagen expression by transforming growth factor-beta 1 in smooth muscle cells.

PURPOSE: Depending on the derivation of vascular smooth muscle cells (SMC), transforming growth factor-beta 1 (TGF-beta 1) has variable effects on proliferation and expression of extracellular matrix. Relatively little is known about TGF-beta 1's effects on human arterial SMC. Therefore, we sought to determine the effects of TGF-beta 1 on human arterial SMC proliferation and 1 alpha(I) procollagen expression. The mechanisms by which TGF-beta 1 regulate type I procollagen expression were also investigated. METHODS: SMC cultures were established from the aorta of transplant donors. Serial doses of TGF-beta 1 were applied, and cellular proliferation assessed by cell counting and tritiated thymidine incorporation. Total cellular ribonucleic acid (RNA) was analyzed by reverse transcription-polymerase chain reaction and Northern blot for changes in 1 alpha(I) procollagen and platelet-derived growth factor (PDGF)-A transcripts. RESULTS: In a dose-dependent manner, TGF-beta 1 inhibited SMC proliferation despite early induction of PDGF-A mRNA. After a delay of 24 hours, TGF-beta 1 increased 1 alpha(I) procollagen expression by 36% compared with control. PDGF-neutralizing antibodies blocked the TGF-beta 1-mediated upregulation of type I procollagen, although PDGF alone had no effect on matrix expression. CONCLUSION: The results indicate that TGF-beta 1 is a potent inhibitor of human arterial SMC proliferation that has a moderate effect on 1 alpha(I) procollagen transcripts. Despite inducing PDGF-A gene expression, TGF-beta 1 is not a mitogen in adult human arterial SMC. TGF-beta 1 regulates SMC type I procollagen expression partly by inducing PDGF-A as a co-factor.

Transforming growth factor-beta 1 inhibits human arterial smooth-muscle cell proliferation in a growth-rate-dependent manner.

BACKGROUND: Proliferation of arterial smooth-muscle cells is central in the development of both atherosclerosis and intimal hyperplasia. The cytokine transforming growth factor-beta 1 (TGF-beta 1) is known to have variable effects on smooth-muscle cell proliferation. Using human arterial smooth-muscle cells, we sought (1) to define the serum concentrations required to maintain cellular proliferation; and (2) to define the effects of TGF-beta 1 on smooth-muscle cell proliferation. METHODS: Smooth-muscle cell cultures were established from the normal aorta of transplant donors. Cells were grown to subconfluent and confluent densities, then incubated in either serum-free media, or 1% or 10% fetal bovine serum (FBS) enhanced media. Cellular proliferation was assayed by cell counting at 24, 48, and 96 hours to establish growth rate. Identical experiments with the addition of recombinant human TGF-beta 1 (5 ng/mliters) were also performed. Studies were done in triplicate for each group, and results expressed as the mean +/- SE. Groups were compared by analysis of variance. RESULTS: In subconfluent cultures, only smooth-muscle cells in 10% FBS proliferated, whereas growth arrest occurred in serum-free media and 1% FBS. In confluent cultures, cells in all media conditions proliferated. TGF-beta 1 had an inhibitory effect in actively proliferating cultures. There was a positive correlation between the inhibitory effects of TGF-beta 1 and smooth-muscle cell growth rate (r = .65; P = 0.005). CONCLUSIONS: When confluent, human arterial smooth-muscle cells continue to proliferate after serum deprivation, suggesting that these cells are capable of conditioning their own medium. TGF-beta 1 inhibits smooth-muscle cell proliferation in a growth-rate-dependent manner. These data suggest that TGF-beta 1 may have a growth-regulatory role in vascular disease by counteracting states of arterial smooth-muscle cell proliferation.

Management of synchronous renal cell carcinoma and aortic disease.

BACKGROUND: We have noted a significant incidence of renal cell carcinoma (RCC) detected during evaluation for aneurysmal and aortoiliac occlusive disease. The approach to synchronous malignancy and aortic disease (staged versus concurrent resection) is controversial, as is the management of incidental RCC (partial versus radical nephrectomy). PATIENTS AND METHODS: We reviewed our experience with incidental RCC in patients undergoing aortic reconstruction between 1991 and 1994. Ninety-seven patients underwent aortic reconstruction for aneurysmal (72), occlusive (20), or embolic disease (5) during the time frame under review. All were men. Of the 80 preoperative computerized tomographic (CT) scans obtained, 7 (9%) demonstrated renal lesions suspicious for RCC. All lesions were explored and excised by partial or radical nephrectomy before heparinization and completion of the planned aortic procedure. RESULTS: The overall mortality rate was 3%. None of the deaths occurred in patients undergoing combined procedures. Four partial and three radical nephrectomies were performed. Of the 7 renal lesions, 2 were complex cysts and 5 were RCC. Both patients with complex cysts were treated with wedge resection. One patient required surgical drainage of a wound abscess after partial nephrectomy. No significant differences were found between preoperative (1.4 +/- 0.1 mg/dL) and postoperative (1.8 +/- 0.2 mg/dL) creatinine levels following combined procedures. On follow-up CT scans done at 6-month intervals (mean follow-up 24 months), no evidence exists of recurrence, metastasis, or graft infection. CONCLUSIONS: This patient population demonstrated an unexpectedly high prevalence of incidental RCC (5 or 80 CTs, 6%). No increase in mortality was found when RCC and aortic disease were treated at the same operation. While partial nephrectomy was associated with one wound infection in this series, it is an effective treatment for small incidental RCC and may avoid unnecessary nephrectomy in patients with benign disease. Base on the high incidence of RCC in this population, we recommend exploration of all suspicious lesions. Nephrectomy can be performed safely in the same setting as aortic reconstruction. Because underlying renal dysfunction is not uncommon in patients with aneurysmal and aortoiliac occlusive disease, nephron-sparing surgery should be considered.

Localization of aortic disease is associated with intrinsic differences in aortic structure.

PURPOSE: While localization of atherosclerosis and aneurysms to the infrarenal aorta has been attributed, in part, to hemodynamic factors, anatomic differences between the proximal and the distal aorta may also be important. Our purpose was to determine the changes in content and organization of major structural proteins (elastin and collagen) throughout the normal human aorta. METHODS: Biochemical analysis for desmosine-isodesmosine (elastin) and hydroxyproline (collagen) content was done by HPLC on complete 1-cm transverse rings removed from the ascending and descending thoracic aorta and abdominal supraceliac, suprarenal, and midinfrarenal aorta. Elastin and collagen content was normalized to lumenal surface area and compared by ANOVA: Light microscopy and optical micrometry were used to determine changes in intimal, medial, and adventitial thickness and number of elastin lamellae at each level. RESULTS: Both collagen/cm2 and elastin/cm2 decrease from the proximal to distal aorta. Collagen content did not differ among the three abdominal segments, but there was a 58% decrease in elastin between the suprarenal and the infrarenal aorta. The proportion of elastin and collagen does not differ throughout the aorta except in the infrarenal aorta where there is decreased elastin relative to collagen. CONCLUSION: Collagen and elastin in the distal aorta bear an increased load as compared to the proximal aorta. The infrarenal aorta differs biochemically and histologically from the remainder of the aorta. A decrease in infrarenal elastin without a corresponding decrease in collagen may effect the compliance and integrity of the distal aorta. These anatomic differences may be important in predisposing the infrarenal aorta to atherosclerosis and aneurysm formation.

Pathogenesis of aneurysms.

We now know our past concepts of AAA pathogenesis to be oversimplified and inaccurate. In fact, the metabolic activity of the aneurysm wall is markedly increased in comparison with normal aorta. It has become clear that AAAs result not from passive dilatation, but from a complex remodeling process involving both the synthesis and degradation of matrix proteins. Our understanding of this process has been advanced by applying molecular biology techniques. Although elastin fragmentation and medial attenuation remain the most striking histological features of AAA tissue, experimental and clinical evidence suggests that the adventitia, which is predominantly collagen, is capable of maintaining the dimensional stability of the aorta in the absence of the medial elastin network. Thus, although factors that result in fragmentation and attenuation of elastin may be important in the etiology of AAA, factors regulating the balance of collagen synthesis and degradation likely determine the rate of AAA progression. The resident inflammatory cells in AAA undoubtedly play an important pathological role in aortic dilatation. Thus, understanding the interaction between aortic mesenchymal cells (smooth muscle cells and fibroblasts) and inflammatory cells (lymphocytes and macrophages) should allow for the identification of genetic factors that predispose to AAA. In addition to the possibility of early identification of patients at risk for AAA, new insights into AAA pathogenesis might allow for development of pharmacological strategies for inhibiting expansion of small AAA.