When is embolic protection needed in lower extremity interventions and how should it be done.

Distal embolization (DE) during lower extremity arterial intervention is a potentially devastating complication which could lead to limb loss. The use of a distal embolic protection device (EP) may prevent significant DE during intervention. Studies investigating the incidence and impact of DE suggest that it is a rare event with low impact on clinical outcomes. The use of EP during peripheral interventions has only been studied in uncontrolled small series with no comparison to unprotected interventions. In spite of the absence of good quality studies, there may be situations where EP is helpful. These situations may be when lesions or devices are particularly prone to produce emboli. The EP device may produce its own serious complications which must be considered prior to their use. In addition these devices are fairly expensive, a factor that needs to be considered when deciding to employ EP. A simple direct comparison of EP vs. no EP during lower extremity intervention could answer many clinical questions surrounding this controversy.

Bradykinin stimulates prostaglandin E2 production and cyclooxygenase activity in equine nonglandular and glandular gastric mucosa in vitro.

REASONS FOR PERFORMING STUDY: There are few data available regarding regulation of prostaglandin (PG) generation by equine gastric mucosae and the role of the cyclooxygenase (COX) isoforms in their production. OBJECTIVES: To: 1) characterise and quantify PGE2 output in vitro; 2) examine the sensitivity of PGE2 production to exogenous bradykinin (BK) exposure; 3) determine the contribution of the COX-1 and COX-2 pathways to basal and BK-stimulated PGE2 production; and 4) measure if BK influences electrogenic ion transport in equine gastric mucosae in vitro. METHODS: Full thickness gastric sheets were obtained from horses at post mortem, stripped of muscle layers and mounted in Ussing chambers. Tissues were exposed to bradykinin (BK, 0.1 micromol/l) either alone, or following pretreatment with a selective COX-2 inhibitor (NS-398, 1 micromol/l) or a nonselective COX inhibitor (piroxicam, 1 micromol/l), or were untreated. RESULTS: BK administration increased PGE2 output from the basolateral but not the apical faces of both tissue types. Piroxicam, but not NS-398, reduced basolateral PGE2 release below control levels in both tissue types. Both piroxicam and NS-398 pretreatment inhibited BK-stimulated PGE2 release. In separate experiments, BK was without effect upon electrophysiological parameters of tissues mounted in Ussing chambers. CONCLUSIONS: PGE2 is produced by the nonglandular and glandular equine gastric mucosae in vitro. Significantly more PGE2 is released basolaterally than apically. BK stimulated the production of PGE2 from the basolateral side of both tissue types. These findings suggest that COX-1 is a significant pathway for basal PGE2 production from the basolateral faces of both nonglandular and glandular equine gastric mucosae in vitro.

Internal iliac artery revascularization as an adjunct to endovascular repair of aortoiliac aneurysms.

PURPOSE: Endovascular repair of aortoiliac aneurysms may be limited by extension of the aneurysm to the iliac bifurcation, necessitating endpoint implantation in the external iliac artery. In such cases the circulation to the internal iliac artery is interrupted. Bilateral internal iliac artery occlusion during endovascular repair may be associated with significant morbidity, including gluteal claudication, erectile dysfunction, and ischemia of the sigmoid colon and perineum. We have employed internal iliac artery revascularization (IIR) to allow endograft implantation in the external iliac artery while preserving flow to the internal iliac artery in patients with aneurysms involving the iliac bifurcation bilaterally. METHODS: A total of 11 IIR procedures were performed in 10 patients undergoing endovascular abdominal aortic aneurysm (AAA) repair (9 men, 1 woman; mean age, 74 years). IIR was accomplished via a retroinguinal incision in 9 cases and a retroperitoneal incision in 2 cases. Six-mm polyester grafts were used for external-to-internal iliac artery bypass in 10 cases and internal iliac artery transposition onto the external iliac artery was used in one case. Endovascular AAA repair was performed using a modular bifurcated device (Talent-LPS, Medtronics, Minneapolis, Minn) after IIR. Bypass graft patency was determined immediately after the surgery, at 1 month, and every 3 months thereafter, using duplex ultrasound scanning and computed-tomography angiography. Mean aneurysm diameters were as follows: AAA, 6.4 +/- 0.7 cm; ipsilateral common iliac, 3.7 +/- 1.0 cm; contralateral common iliac, 3.9 +/- 0.8 cm. RESULTS: Successful IIR and endovascular AAA repair were accomplished in all cases. No proximal, distal, or graft junction endoleaks occurred. Two patients demonstrated retrograde aneurysm side-branch endoleaks originating from the lumbar arteries. One thrombosed spontaneously within 3 months. One perioperative myocardial infarction occurred. Reduction in aneurysm size was documented in 5 aortic, 5 ipsilateral iliac, and 3 contralateral iliac aneurysms. Gluteal claudication, erectile dysfunction, colon and perineal ischemia, and mortality did not occur. All IIRs have remained patent during a follow-up period of 4 to 15 months (mean, 10.1 months). CONCLUSIONS: IIR may be used with good short-term to intermediate-term patency to prevent pelvic ischemia in patients whose aneurysm anatomy requires extension of the endograft into the external iliac artery. This may allow endovascular AAA repair to be performed in patients who might otherwise be at risk for developing complications associated with bilateral internal iliac artery occlusion.

Endovascular repair of para-anastomotic aneurysms of the aorta and iliac arteries: preferred treatment for a complex problem.

PURPOSE: Standard surgical repair of para-anastamotic aneurysms (PAAs) of the abdominal and thoracic aorta and the iliac arteries has been associated with high morbidity and mortality rates. We reviewed our continuing experience with endovascular repair of these lesions to determine whether this approach is favorable and durable. METHODS: All patients with PAAs of the aorta or iliac arteries who underwent endovascular treatment of their lesions between August 1993 and July 1999 were prospectively followed up, and data on age, previous aortic pathology and surgery, size of PAA, time to diagnosis, and symptoms at presentation were recorded. Preoperative, intraoperative, and postoperative imaging studies were analyzed. All patients had endovascular stent-grafts placed under digital fluoroscopic guidance in the operating room. Data on intraoperative and postoperative complications, mortality, and endoleaks were reviewed. RESULTS: From August 1993 to July 1999, 28 patients (20 men, 8 women) had 35 PAAs of the aorta or iliac arteries. There were 5 thoracic aortic, 12 abdominal aortic, and 18 iliac artery PAAs. Three patients had a contained rupture of their PAA. All patients who had originally undergone reconstruction for occlusive disease had lesions consistent with false aneurysms, whereas 73% of the aortic or iliac PAAs in patients originally treated for aneurysm disease appeared to be true aneurysms. Thirty-four of 35 PAAs were successfully excluded with stent-grafts (97%). There was one death at 30 days (3.6%) in a patient who was successfully treated endovascularly for a contained rupture of a thoracic PAA. There were four major postoperative complications (14.2%) in the 28 patients who were treated. One patient had continued perfusion of a thoracic aortic PAA (type I endoleak). The in-hospital length of stay after endovascular repair of PAA was 4 days (range, 1-18 days). The mean follow-up period was 21 months (range, 1-68 months). CONCLUSION: Endovascular repair of aortic and iliac artery PAAs is technically feasible and provides a high rate of lesion exclusion. Morbidity and mortality rates appear lower than those reported for open surgical repair. These patients can typically be discharged by the second postoperative day. Endovascular therapy for stable ruptured PAAs can be successfully performed and should be considered as an option only when appropriate devices and expertise are available. For uncomplicated PAAs of the aorta and iliac arteries, endovascular therapy may be more favorable than surgical repair.

Intentional internal iliac artery occlusion to facilitate endovascular repair of aortoiliac aneurysms.

PURPOSE: The safety of intentional occlusion of patent internal iliac arteries (IIAs) to facilitate the endovascular repair of aortoiliac artery aneurysms (abdominal aortic aneurysms [AAAs] and iliac aneurysms [IAs]) was evaluated. METHODS: We analyzed the techniques and clinical sequelae of selective occlusion of one or both IIAs in 103 patients and correlated these findings with the results of preoperative angiograms to identify vascular anatomy that may predict postoperative pelvic ischemia. To quantify the clinical presentation of pelvic ischemia, we developed these criteria: class 0, no symptoms; class I, nonlimiting claudication with exercise; class II, new onset impotence, with or without moderate to severe buttock pain, leading to physical limitation with exercise; class III, buttock rest pain, colonic ischemia, or both. IIA occlusion was achieved in 100% of the patients by means of either catheter-directed embolization or orificial coverage with a stent-graft. No patient in this study had angiographic evidence of significant visceral occlusive disease before the procedure. Sixty-four patients had isolated AAAs, 23 patients had AAAs and IAs, and 16 patients had isolated IAs. Ninety-two patients had one IIA selectively occluded, and 11 patients had both IIAs selectively occluded. RESULTS: After IIA occlusion, 12 patients were categorized in class I, 9 patients were categorized in class II, and 1 patient was categorized in class III, for a total of 22 patients (21%) with pelvic ischemia. Sixteen (17%) of 92 patients had unilateral IIA occlusions, and six (17%) of 11 patients had bilateral IIA occlusions. Five patients in class I improved and had no symptoms within 1 year, and one patient in class II was downgraded to class I because of improved symptoms. Two unique preoperative angiographic findings were identified in the remaining 16 patients (16%) with chronic pelvic claudication: (1) stenosis of the remaining IIA origin (> 70%) with nonopacification of more than three of the six IIA branches (63%); and (2) small caliber, diseased or absent medial and lateral femoral circumflex arteries ipsilateral to the side of the IIA occlusion (25%). One patient with class III ischemia died of cardiovascular collapse associated with colon infarction caused by either acute ischemia or particulate embolization. CONCLUSION: The incidence of pelvic ischemia after IIA occlusion is 20% immediately after endovascular aortoiliac aneurysm repair. A total of 25% of patients had no symptoms within 1 year. Two preoperative radiologic findings may help identify patients who are at risk for pelvic ischemia: stenosis of the patent IIA and disease deep femoral ascending branches ipsilateral to the occluded IIA. The risk of colon ischemia appears to be small after selective IIA occlusion to facilitate endovascular AAA repair.

Ancillary techniques to facilitate endovascular repair of aortic aneurysms.

PURPOSE: The ability to treat abdominal aortoiliac aneurysms and thoracic aortic aneurysms may be limited by coexisting arterial disease. Device deployment may be impaired by occlusive disease and tortuosity of the arteries used to access the aneurysm or by suitability of the implantation sites. In this study we describe the auxiliary procedures performed to circumvent these obstacles and thereby enable endovascular aneurysm repair. PATIENTS AND METHODS: Between January 1, 1993, and December 31, 1999, 390 patients treated for aneurysm of the aorta with endovascular devices were entered prospectively in a vascular registry. Fifty (12%) of the 390 patients required adjunctive surgical techniques to (1) create or extend the length of the proximal or distal device implantation site or (2) permit device navigation through diseased iliac arteries. Auxiliary techniques used to extend or enhance implantation sites were elephant trunk graft (n = 2), the construction of renovisceral bypass grafts (n = 1), and subclavian artery transposition (n = 2). Plication of the common iliac artery at its bifurcation was performed in conjunction with femorofemoral bypass graft in nine patients to allow preservation of pelvic circulation by avoiding internal iliac artery sacrifice. Construction of a bypass graft to transpose the internal iliac artery orifice was performed in one patient. The auxiliary techniques used to facilitate device navigation were iliac artery angioplasty or stenting (n = 8), external iliac artery endovascular endarterectomy or straightening (n = 14), endoluminal iliofemoral bypass conduit (n = 5), and the construction of an open iliofemoral bypass conduit (n = 8). RESULTS: Successful deployment of the endovascular devices was achieved in 49 (98%) of 50 patients. Auxiliary techniques were successful in providing access for endovascular device deployment in all 35 patients (100%). Mean follow-up for techniques to facilitate device navigation is 26 months for endovascular procedures and 42 months for the open bypass graft construction patients; no occlusions were observed at this moment. There were five patients with incisional hematomas that did not necessitate intervention. Fourteen (94%) of 15 patients underwent successful device implantation after the auxiliary maneuvers to enhance implantation site. Mean follow-up for implantation site manipulation is 28 months. One of the subclavian transpositions had a new onset of Horner's syndrome, two of nine patients who had common iliac artery ligated had retroperitoneal hematomas that did not necessitate interventions, and no colon ischemia was seen. The patient who underwent nonanatomic bypass grafting of viscero-renal arteries had a retroperitoneal hematoma that necessitated reexploration. CONCLUSIONS: Significant coexisting arterial disease may be encountered in patients with aortic or iliac aneurysms. Identification of coexisting arterial diseases is essential to help tailor the appropriate supplemental surgical procedure to allow the performance of endovascular aneurysm repair in patients who would otherwise require open surgical repair.

Histopathologic analysis of endovascular stent grafts from patients with aortic aneurysms: Does healing occur?

BACKGROUND: Research with animal models has demonstrated tissue healing of endovascular grafts in both native arterial segments and in experimentally created arterial aneurysms. Fundamental to the successful clinical use of endovascular grafts for the treatment of aneurysmal disease is the creation of a permanent hemostatic seal between the graft ends and the arterial wall. Characteristics of this healing process in patients with aneurysmal disease have not been fully studied. In this study, we analyzed the macroscopic and histopathologic changes of the arterial wall after endovascular repair of aortic aneurysms. METHODS: Over a 7-year period, 313 patients were treated with endovascular grafts to exclude arterial aneurysms of the thoracic and abdominal aorta. Of these patients, 11 had their endovascular grafts recovered for analysis. Five graft specimens were recovered during subsequent open aortic surgery. Six grafts were recovered at autopsy after the death of the patient of causes unrelated to the patient's endovascular graft. All specimens were fixed in formalin. Histologic analysis included light microscopy with hematoxylin and eosin and trichrome stains. Well-preserved specimens were selected after light microscopic examination and postfixed in 3% buffered glutaraldehyde for electron microscopy. The aortas from autopsy specimens were removed en bloc and fixed in formalin; representative regions of each graft were sectioned for analysis. Adherence of the graft to the vessel wall was categorized as densely adherent or easily separated after graft explantation. Traction applied to the graft-aortic anastomosis was equal to traction generated by suspending a standardized 2-kg weight. Infrarenal graft specimens were obtained with supraceliac aortic clamping, longitudinal aortotomy, and graft sampling before endograft revision. RESULTS: In eight patients, endograft fixation was found to be firmly adherent to the arterial wall. A translucent film of fibrinous material was consistently seen across the entire luminal surface of the endograft. Light and electron microscopy failed to demonstrate an endothelial layer or organized pseudointima at the graft-artery interface. CONCLUSION: Despite suggestive experimental data regarding endograft healing in animals, minimal graft incorporation was apparent in the stent grafts recovered in this study. A greater emphasis on the construction and mechanism of fixation of endograft attachment systems will be important for long-term device function.

Current use of endovascular grafts for the treatment of abdominal aortic aneurysms.

The development of endovascular techniques for the treatment of abdominal aortic aneurysms has significantly reduced the major morbidity associated with standard surgical repair. The indications for use of endovascular grafts and the limitations of their use have not been fully defined. The effectiveness of the numerous commercially fabricated devices is currently being evaluated. This article describes the general principles of use for endovascular devices and details the features and results for the devices in current use.

Anatomic exposures in thoracoabdominal aortic surgery.

Thoracoabdominal aortic aneurysm repair requires exposure of long segments of the aorta. This often results in large, debilitating incisions that can compromise pulmonary physiology significantly and result in severe pain. Preoperative preparation and positioning of the patient as well as careful planning of the incision based on the individual's anatomy are required for successful aortic exposure. Alternative approaches such as varying the skin incision location and performing submuscular dissection can reduce postoperative discomfort. Rib resection and double thoracotomy may be needed to expose enough aorta to allow safe proximal and distal control. Improved understanding of the pathophysiology of postoperative complications may alter the approach to aortic and visceral vessel exposure and reattachment. In addition, endovascular technology continues to advance, allowing for more applications in thoracic aortic disease. A combined open and endovascular approach to thoracic aortic aneurysms may minimize the morbidity and mortality by decreasing the physiologic insult normally incurred by long thoracoabdominal incisions.

Tolerance induction permits the development of graft-versus-host disease: donor-mediated attack following small bowel transplantation in mixed chimeras.

The induction of tolerance to organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. We have shown that tolerance induced through the creation of mixed allogeneic bone marrow chimeras allows for the long-term engraftment of cardiac and small bowel allografts across strong multiple major histocompatibility barriers. The possibility that tolerance might render the host susceptible to graft-versus-host disease (GVHD) has not been investigated in this or other models of tolerance. To test this possibility chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post bone marrow transplant (BMTx) by flow cytometry of lymphocytes from reconstituted animals. ACI/Lew chimeras (ALC), Lewis/ACI F1 (LACF1), and Lewis (LEW) rats all received heterotopic ACI vascularized small bowel grafts. A second group of chimeras received small bowel grafts from ACI rats pretreated with low dose irradiation to eliminate T-cells from the graft. LEW-->LEW small bowel isografts were also performed. Animals were examined for evidence of GVHD by clinical signs and histologic examination of biopsied tissues. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 rats developed severe lethal GVHD following ACI small bowel transplant. Bone marrow chimeras, ALC (n = 6), developed fatal GVHD in a similar fashion after receiving a small bowel transplant. LEW-->LEW isografts and chimeras receiving bowel from irradiated ACI rats survived long term without GVHD while ACI-->LEW allogeneic transplants all underwent acute rejection. GVHD or its absence was confirmed histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras (1.87) and LACF1 (5.4) receiving allografts, but not in isografts or chimeras receiving irradiated allogeneic transplants. Analysis of cytokines in the tongues of rats undergoing GVHD showed elaboration of Th1 type proinflammatory cytokines which was not seen in isografted rats or rats receiving preirradiated small bowel. These results demonstrate that tolerance induction through mixed chimerism results in susceptibility to small bowel induced GVHD. Preirradiating the donor bowel prior to SBTx can prevent GVHD.

Tolerance induction by intrathymic inoculation prevents chronic renal allograft rejection.

BACKGROUND: These experiments investigated the ability of the donor-specific unresponsiveness created by the intrathymic inoculation of donor alloantigen to effectively prevent chronic rejection in an established rat model of chronic renal allograft rejection. METHODS: Three study groups were examined: (1) Allograft controls--F-344 rats received a Lewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls--F-344 rats received an F-344 renal isograft and low-dose CsA; (3) experimental group--F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis bone marrow. Twenty-one days after bone marrow transplant, these animals received a Lewis renal allograft. RESULTS: Allograft controls demonstrated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analysis revealed increased CD4+ T cells infiltrating the cortex of the allograft controls. Cytokine interferon-gamma and interleukin-2 transcripts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcriptase-polymerase chain reaction. Analysis of tolerant grafts by flow microfluorimetry and genomic DNA amplification could not detect chimerism to a level of < 0.1%. CONCLUSION: IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.

Graft versus host disease in rats made tolerant for organ allografts.

Tolerance for organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. A potential hazard of tolerance is the susceptibility to graft vs host disease (GVHD) due to unresponsiveness to alloantigen. This study sought to determine if our model of tolerance induction results in susceptibility to GVHD. Chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post-BMTx by flow cytometric analysis of recipient spleens for the presence of ACI cells. ACI/Lew chimeras (ALC), animals that reconstituted only with syngeneic (Lewis) marrow (so-called failed chimeras), and ACI/Lew F1 (LACF1) hybrid rats were all given 200 x 10(6) ACI splenocytes i.v. Animals were examined for evidence of GVHD. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 (n = 6) rats developed severe lethal GVHD following ACI splenocyte injection. Similarly, ALC (n = 6) developed fatal GVHD. Animals that reconstituted only with syngeneic Lewis marrow (failed chimeras) showed no signs of illness. GVHD was confirmed histologically and immunohistochemically. Failed chimeras receiving ACI splenocyte challenge showed no evidence of GVHD histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras and hybrids but not in the failed chimeras. We conclude that tolerance induction by mixed chimerism results in susceptibility to GVHD if enough donor lymphoid tissue is given to the host at the time of organ transplant. Animals that are not mixed chimeras (failed bone marrow transplant) rejected the allogeneic splenocytes as evidenced by their lack of disease. Tolerance may therefore make the host defenseless against fatal GVHD.

Induction of specific tolerance through mixed hematopoietic chimerism prevents chronic renal allograft rejection in a rat model.

BACKGROUND: Chronic rejection is the leading cause of late graft loss in kidney transplantation. We tested the ability of mixed hematopoietic chimerism to prevent chronic renal allograft rejection in an established rat model and described possible mechanisms responsible for this tolerance. METHODS: Mixed hematopoietic chimerism was established in lethally irradiated F-344 rats by reconstitution with Lewis bone marrow. Four groups (n = 5 each) received orthotopic kidney transplants: (1) allograft controls, (2) isograft controls, (3) experimental chimeras, and (4) specificity control. After 120 days kidney grafts were examined histologically, immunohistochemically, and for cytokine interferon-gamma, interleukin-2 (IL-2), IL-4, and IL-10 gene transcripts by means of reverse transcriptase polymerase chain reaction techniques. RESULTS: Allograft control group exhibited severe parenchymal fibrosis; isograft control and chimera groups failed to develop this lesion. Immunohistochemical analysis revealed increased CD8+ lymphocytes and ED-1+ monocyte-macrophages infiltrating the tubulointerstitium of control allografts. Interferon-gamma and IL-2 were absent in isografts. IL-4 was absent and IL-10 was positive in all grafts. Chimeras promptly rejected third-party allografts. CONCLUSIONS: Induction of specific tolerance through mixed hematopoietic chimerism prevents chronic renal allograft rejection. These results support the hypothesis of an immunologic basis of chronic rejection and advance previous observations that the induction of specific tolerance enables long-term solid organ transplantation without the use of immunosuppression.

Power orientation: a study of female nurse and non-nurse managers.

Researchers studied the power orientations of female managers as related to career choice, education level, age, and years as a manager. The questionnaire includes six orientations to power: 1) power as good; 2) power as resource dependency; 3) power as instinctive drive; 4) power as political; 5) power as charisma; and 6) power as control and autonomy. Discerning power may explain how one perceives the managerial position.

Modified method for determining carcinoembryonic antigen in the presence of human anti-murine antibodies.

The increasing use of monoclonal antibodies (MAbs) for disease diagnosis and therapy has created a class of patients at risk for systematic error in clinical testing due to interference by human anti-murine antibodies (HAMA). HAMA interference is often difficult to detect and can cause either an increase or a decrease in apparent concentrations of antigen present. We undertook a clinical study to test a HAMA-resistant enzyme immunoassay (EIA) format for carcinoembryonic antigen (CEA) determination. Using the Food and Drug Administration-approved CEA-EIA Monoclonal One-Step Assay (Abbott) with the addition of an acid/heat extraction of patients' specimens, we found that the resulting CEA values accurately reflected the patients' status. We demonstrated that the acid/heat-extracted specimens yield linear dilution curves and show analytical recoveries of added CEA in the range of 76-123% in HAMA-positive specimens and 86-103% in HAMA-negative specimens. The correlation of CEA values in extracted vs unextracted specimens from 184 patients and control subjects was 0.9963. The CEA detection limit of the assay was 1.6 micrograms/L for the extracted samples.