Evolution of vascular fellowship training in the new era of endovascular techniques.

PURPOSE: The endovascular technique has revolutionized the treatment of infrarenal abdominal aortic aneurysm (AAA). At our institution, we examined the impact of an endovascular program on the traditional operative training of the vascular fellows in the treatment of infrarenal AAA. METHODS: We examined the records of our vascular fellows' experience from July 1995 to May 2000. We introduced the endovascular treatment for infrarenal AAA in 1995. RESULTS: The fellows have performed increasing numbers of endovascular cases each year, with a predicted number of 124 cases for 1999-2000. However, despite an increase in the overall volume of patients with infrarenal AAA (102 cases in 1998-1999 and a predicted 160 cases in 1999-2000), the trainees will experience a reduction in the number of open AAAs from 61 cases in 1998-1999 to a predicted 36 cases in 1999-2000. However, the volume of open suprarenal AAA has also increased from eight cases in 1998 to 1999 to a predicted 24 cases in 1999-2000. With no significant change in the open aortoiliac occlusive cases from previous years, the current fellows will graduate with a similar volume of open aortic procedures as their predecessors. CONCLUSION: With the recent advances in endovascular technology, our traditional operative approach to the treatment of AAA disease may be lacking in the training of future vascular surgeons. At our institution, although fewer open infrarenal AAA cases were performed, the trainees have maintained the open aortic experience by performing an increased volume of suprarenal AAAs. We have to critically reevaluate and redefine what constitutes adequate vascular fellow experience in the surgical treatment of abdominal aortic aneurysms.

Current results of surgical therapy for chronic mesenteric ischemia.

BACKGROUND: Although recognition of chronic mesenteric ischemia has increased in recent years, this disorder has continued to present diagnostic and therapeutic challenges. OBJECTIVE: To examine the modern results of surgical revascularization for chronic mesenteric ischemia. DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: The management of 24 consecutive patients (mean +/- SEM age, 58 +/- 3 years; 5 men, 19 women) who were undergoing surgical treatment of chronic mesenteric ischemia between 1986 and 1996 was reviewed. INTERVENTION: Surgical mesenteric revascularization. MAIN OUTCOME MEASURES: Postoperative course, long-term graft patency rate, and long-term symptom-free survival rate. RESULTS: The most frequent presenting symptoms were postprandial abdominal pain (18 patients [75%]) and weight loss (14 patients [58%]). Less specific complaints included nausea and vomiting (8 patients [33%]), diarrhea (7 patients [29%]), and constipation (4 patients [17%]). Atherosclerotic risk factors were common, including tobacco use (20 patients [83%]), coronary artery disease (10 patients [42%]), and hypertension (10 patients [42%]). The cause was identified as atherosclerosis in 21 patients, median arcuate ligament compression in 2 patients who were monozygotic twins, and Takayasu arteritis in 1 patient. Lesions were localized to all 3 major visceral vessels (celiac artery, superior mesenteric artery [SMA], and inferior mesenteric artery) in 8 patients, celiac artery and SMA in 13, SMA alone in 2, and SMA and inferior mesenteric artery in 1. Seventeen patients underwent antegrade reconstructions from the supraceliac aorta to the SMA and/or celiac artery; 7 patients underwent revascularization by use of a retrograde bypass that originated from the infrarenal aorta or a prosthetic graft. There were no perioperative deaths although 1 patient died in the hospital 6 weeks after early graft failure and sepsis (overall in-hospital mortality, 4%). Follow-up ranged from 3 months to 10 years (median, 2.4 years). The mean +/- SEM 5-year primary graft patency rate, as objectively documented by use of contrast angiography or duplex scanning in 19 of 24 patients, was 78% +/- 11%. Primary failure was documented in 3 patients (at 3 weeks, 5 months, and 7 months). Two patients required a thrombectomy; 1 of these patients subsequently died of an intestinal infarction. The mean +/- SEM 5-year survival rate by use of life-table analysis was 71% +/- 11%. No patient with a patent graft experienced a symptomatic recurrence. CONCLUSIONS: Chronic mesenteric ischemia is usually a manifestation of advanced systemic atherosclerosis. Symptoms almost always reflect midgut ischemia in the distribution of the SMA. An antegrade bypass from the supraceliac aorta can be performed with acceptable operative morbidity and is currently the preferred reconstructive technique. Surgical revascularization affords long-term symptom-free survival in a majority of patients with chronic mesenteric ischemia.

TNF-alpha and IL-1 upregulate membrane-bound and soluble E-selectin through a common pathway.

BACKGROUND: Endothelial cell adhesion molecules such as E-selectin promote the capture of neutrophils (PMN) in the microcirculation and initiate the inflammatory response. In contrast, when "shed" into the microcirculation, soluble E-selectin can bind PMN in the blood stream, reducing the number available for adhesion to injured tissue. These experiments were designed to better characterize the molecular response to cytokines and the balance between cell surface (bound) and soluble (unbound) E-selectin. METHODS: Cultured human umbilical veins, exposed to human recombinant TNF-alpha or IL-1 (10 pg/ml), were analyzed for E-selectin mRNA induction (Northern blot), E-selectin cell surface expression (flow cytometry), and sE-selectin release (ELISA). Transcriptional regulation was analyzed via Raf kinase dominant negative gene transfection. RESULTS: E-selectin mRNA expression was markedly increased at 2 h and sustained through 8 h. No further induction was noted at 12 h. Upregulation of cell surface E-selectin was noted (mean fluorescence) as early as 2 h for TNF-alpha (baseline, 12.28 +/- 1.32; TNF-alpha, 23.03 +/- 1.81) or 4 h for IL-1 (baseline, 12.28 +/- 1.32; IL-1, 70.00 +/- 3.04) with maximum expression at 6 h (TNF-alpha, 118.8+/-15; IL-1, 94.11 +/- 9. 34). Expression returned to baseline levels by 24 h. Soluble E-selectin (ng/ml) assays demonstrated later increases beginning at 12 h (TNF-alpha, 0.313 +/- 0.077; IL-1, 0.159 +/- 0.075) and continuing through 24 h (TNF-alpha, 0.340 +/- 0.062; IL-1, 0.157 +/- 0.030). Transfection of endothelial cells with Raf kinase 301 dominant negative gene resulted in proportionate decreases in the peak expression in both surface (bound) E-selectin (TNF-alpha, 51. 7%; IL-1, 29.6%) and sE-selectin (TNF-alpha, 49.2%; IL-1, 34.5%). CONCLUSION: The temporal sequence of late decreases in cell surface E-selectin accompanied by increases in soluble E-selectin indicates that the source of E-selectin in the microcirculation is shed receptors rather than synthesis of a different type of receptor. Enhancement of such "shedding" may decrease PMN adhesion to injured tissue and have therapeutic potential.

Cytokine-induced increases in endothelial permeability occur after adhesion molecule expression.

BACKGROUND: Transmigration of neutrophils (PMNs) through endothelial cell tight junctions is a critical stage in the tissue injury of ischemia-reperfusion (I/R). Although cytokines are released in I/R, it is unclear whether cytokines directly increase permeability or this phenomenon requires both expression of cell adhesion molecules and PMN adhesion-activation. METHODS: We exposed confluent monolayers of human umbilical vein endothelial cells to physiologic concentrations of interleukin-1 (10 pg/ml) and tumor necrosis factor-alpha (10 pg/ml) in the absence of PMNs. Tight junction permeability was quantified with both transendothelial electrical resistance and albumin flux, whereas expression of endothelial-leukocyte adhesion molecule-1 was measured by flow cytometry (t test p < 0.05). RESULTS: Stimulation with tumor necrosis factor-alpha or interleukin-1 produced maximal transendothelial electrical resistance decreases at 12 hours with return to baseline at 24 hours. Increases in albumin flux began at 6 hours, with maximum effects at 24 hours. These changes occurred soon after maximal expression of endothelial-leukocyte adhesion molecule-1 at 4 hours. CONCLUSIONS: Cytokines induced increases in both cell adhesion molecule expression and endothelial permeability. This sequence of events is consistent with direct cytokine effects on cytoarchitecture, because it occurred without the adhesion-activation of PMNs.

Physiologic concentrations of TNFalpha and IL-1beta released from reperfused human intestine upregulate E-selectin and ICAM-1.

Intestinal ischemia-reperfusion (I/R) causes local and distant tissue injury via neutrophil (PMN) activation and adhesion. Endothelial cell adhesion molecules (E-selectin, ICAM-1) mediate the adhesion and transmigration of PMN in the microcirculation. Expression of these receptors is influenced by cytokines. To determine the physiologic concentrations of two specific cytokines involved in I/R, tumor necrosis factor (TNF) and interleukin-1 (IL-1), human intestinal segments were exposed to 30 min of ischemia followed by reperfusion. Venous effluent samples were obtained; enzyme immunoassays measured maximum concentrations of TNF (30.5 +/ 1.0 pg/ml) and IL-1 (59.0 +/- 6.0 pg/ml). Cultured human endothelial cells were then exposed to physiologic concentrations of human recombinant TNF (10 pg/ml) and IL-1 (10 pg/ml), individually and in combination. Flow cytometric analysis of receptor expression demonstrated upregulation of E-selectin as early as 2 hr (P < 0.05) with maximum effects at 4 hr. At 4 hr, E-selectin expression (% shift from baseline) was greater with TNF and IL-1 combined (50.9 +/- 2.9, P < 0.01) than with either cytokine alone (TNF 34.6 +/- 4.0; IL-1 23.5 +/- 4.0, P < 0.01). ICAM-1 receptor expression began at 4 hr with maximum effects at 24 hr. ICAM-1 expression after TNF and IL-1 exposure (15.4 +/- 1.3, P < 0.001) was also greater than TNF (10.9 +/- 0.3, P < 0.01) or IL-1 (3.1 +/- 1.5) alone. TNF and IL-1 are present in venous effluent in concentrations capable of increasing PMN adhesion in the microcirculation. These findings support a role for these cytokines in local and distant organ injury from I/R. Since combined effects are greater than either cytokine alone, antagonism of both TNF and IL-1 may be required for a therapeutic benefit in clinical applications.

Patency and blood flow in gas denucleated arterial prostheses.

Biomaterials exposed to blood often fail due to thrombosis. Gas nuclei (air) in the material are thrombogenic and a potential cause of failure. The effects of gas nuclei on patency and blood flow were studied in 4 mm diameter arterial grafts (Gore ePTFE; Johnson and Johnson Vitagraft ePTFE; Bard ACG EXS) in the femoropopliteal position of dogs. Control and denucleated (air-free) grafts were implanted bilaterally. Grafts were denucleated by immersion in degassed saline and exposure to 4 torr vacuum and 3,000-20,000 psig pressure. Graft patency was determined at harvest in 46 dogs. Blood flow was measured with acoustic flow probes in eight dogs. Denucleated graft patency was 60% after 2 days of implant while control patency was 22% (P < .05). Measured blood flow was higher in denucleated grafts than in control grafts (P < .02) in 4 of 5 dogs which had significantly different flows. Patency and flow decreased to zero for both control and denucleated grafts over periods of up to 80 days. Air in the control grafts may have been absorbed within several days, leading to late similarity with the denucleated grafts. Thus, removing the air from 4 mm ePTFE grafts decreased acute thrombosis and increased the patency.

Evaluation of solutions for small intestinal preservation. Biochemical changes as a function of storage time.

A number of organ preservation solutions have been formulated to slow the inevitable progression of ischemic injury, thus prolonging the storage time between removal and implantation. As adenine nucleotide content has been shown to correlate with the functional recovery of transplanted livers and hearts, this study investigated the effects of 24 hr of storage in three preservation solutions, saline (SA), Euro-Collins (CO), and University of Wisconsin (UW) on adenine and nicotinamide adenine nucleotides and inosine content of the rat small intestine. Significant biochemical differences were found between segments as early as after the initial perfusion when the inosine content was higher in UW-perfused than CO- or SA-perfused segments. After 2 hr of storage in CO solution and after 6 and 24 hr in both CO and UW solutions, the ATP content was higher than in SA-stored segments. In addition to inosine, which was significantly higher at all time points for UW-stored segments, the AMP and total adenine nucleotide content of UW-stored segments at 24 hr was significantly higher than SA- or CO-stored segments. After 24 hr of storage, those segments stored in UW were able to utilize significantly more oxygen than SA-stored. These data provide biochemical evidence supporting the advantages of CO and UW storage solutions over SA for preservation of small intestine segments.