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Experimental hindlimb ischemia increases neutrophil-mediated matrix metalloproteinase activity: a potential mechanism for lung injury after limb ischemia
Plitas, George; Gagne, Paul J; Muhs, Bart E; Ianus, Ioana A; Shaw, Jason P; Beudjekian, Mira; Delgado, Yara; Jacobowitz, Glenn; Rockman, Caron; Shamamian, Peter
Acute limb ischemia initiates a systemic inflammatory response, including pulmonary polymorphonuclear leukocyte (PMN) sequestration and acute lung injury. Lung injury is partly attributed to release by PMN's of extracellular matrix (ECM) modifying metalloproteinases (MMPs). We hypothesized that acute hindlimb ischemia (HI) would increase MMP activity in the lung and other organs and that systemic neutrophil depletion before HI would block this effect.Seventeen FVB/N Tie2/LacZ-182 SATO female mice were randomly divided into four groups: HI + PBS (Group 1), HI + antineutrophil antibody (Group 2), HI + isotype matched control antibody (Group 3), and no HI + PBS (Group 4). HI was achieved by unilateral femoral artery ligation. Neutrophil depletion was confirmed. Three days postligation, lung, liver, and kidney were harvested. MMP-2 and -9 expression and activation (gelatin zymography) and membrane type-1 MMP (MT1-MMP, western blotting) were quantified by densitometry and NIH Image Analysis software. Statistical significance was determined with an analysis of variance.Zymograms revealed a 46% increase in pulmonary proMMP-9 in Group 1 versus Group 4 (6,107 +/- 472 [mean +/- SEM] densitometry units [DU] versus 3,287 +/- 675 DU, p < 0.05). A similar trend was observed for active MMP-9 (3,189 +/- 541 DU versus 1,417 +/- 927 DU, p = 0.16). Neutrophil depletion (Group 2) decreased proMMP-9 levels by 51% (2,996 +/- 314 DU versus 6,107 +/- 472 DU, p < 0.05) and active MMP-9 by 75% (810 +/- 444 DU versus 3,189 +/- 541 DU, p < 0.05) compared with Group 1. Active MMP-2 increased 51% after HI (Group 1, 3,230 +/- 86 DU versus Group 4, 1,599 +/- 327 DU, p < 0.05). Neutrophil depletion decreased the HI-induced activation of MMP-2 by 43% (Group 2, 1,829 +/- 471 DU versus Group 1, 3,230 +/- 86 DU, p < 0.05).HI increases pulmonary proMMP-9, active MMP-9, and active MMP-2 levels. Neutrophil depletion blocks this effect. These data suggest that acute limb ischemia leads to PMN-mediated changes in MMP activity
PMID: 12742210
ISSN: 1072-7515
CID: 34656
Initial successful management of type I endoleak after endovascular aortic aneurysm repair with n-butyl cyanoacrylate adhesive
Maldonado, T S; Rosen, R J; Rockman, C B; Adelman, M A; Bajakian, D; Jacobowitz, G R; Riles, T S; Lamparello, P J
OBJECTIVE: Transcatheter embolization with coils and other agents has been described as a treatment method for type II endoleak after endovascular aortic aneurysm repair (EVAR). Type I endoleak has not been treated commonly with such therapies, although most investigators believe they warrant definitive intervention. The liquid adhesive n-butyl 2-cyanoacrylate (n-BCA) is often used to treat congenital arteriovenous malformations. The objective of this study is to report our initial experience in treating type I endoleak with n-BCA and with a variety of other interventions. METHODS: A retrospective review was performed of 270 patients who underwent EVAR at our institution between January 1994 and December 2002. Of these, 24 patients had type I endoleak (8.9%), diagnosed either intraoperatively (n = 13, 52%) or during follow-up (n = 12, 48%). Among these 24 patients, 17 had proximal leaks and the remaining 8 patients had distal leaks. These cases form the focus of this study. RESULTS: Twenty-two leaks required endovascular intervention, with the following success rate: n-BCA, 12 of 13 cases (92.3%); extender cuffs, 4 of 5 cases (80%); coils with or without thrombin, 3 of 4 cases (75%). In one patient with persistent endoleak despite attempted endovascular intervention the device ultimately was surgically explanted, and the patient did well. Of six patients with endoleak initially managed expectantly, two eventually underwent attempts at definitive intervention, both with n-BCA. Three sealed spontaneously before definitive intervention could be performed; and in one 97-year-old patient who refused intervention, the aneurysm subsequently ruptured and the patient died. In total, 13 patients with type I endoleak underwent n-BCA transcatheter embolotherapy. No serious complications were directly related to this therapy. Colon ischemia developed in one patient, and was believed to be a result of thromboembolism during wire and catheter manipulation rather than n-BCA treatment. Twelve of these 13 leaks remain sealed at mean follow-up of 5.9 months (range, 0-19 months). CONCLUSION: Our initial use of n-BCA occlusion suggests that it may be an effective and safe method of treatment of type I endoleak after EVAR. In particular, n-BCA embolotherapy may be especially useful in treating type I endoleak not amenable to placement of extender cuffs. Larger case series and longer follow-up are needed before this treatment is more broadly recommended. Type I endoleak after EVAR can be treated successfully with a variety of endovascular methods, and surgical explantation is rarely required
PMID: 14560210
ISSN: 0741-5214
CID: 39031
The benefits of carotid endarterectomy in the octogenarian: a challenge to the results of carotid angioplasty and stenting
Rockman, Caron B; Jacobowitz, Glenn R; Adelman, Mark A; Lamparello, Patrick J; Gagne, Paul J; Landis, Ronnie; Riles, Thomas S
Proponents of carotid angioplasty and stenting (CAS) believe that this technique would be preferred over carotid endarterectomy (CEA) for the high-risk patient. Presumably this would include patients over 80 years of age. However, a recent large series of patients undergoing CAS revealed a 16% incidence of nonfatal strokes and deaths for patients over the age of 80; these results were significantly worse than those for younger patients undergoing CAS. The objective of this study was to reassess results of CEA in patients over 80, and to compare surgical results with the published results of CAS in this patient group. A review was conducted of a prospectively maintained database of all carotid surgery performed at our institution. Primary CEA that took place from 1997 through 1999 were included for analysis (n = 698). Our institutional results were compared with representative results from a recently published large series of CAS. Our analysis showed that CEA can be performed safely in the octogenarian, and results are equivalent to those of younger patients. CEA appears to have significantly better results in the octogenarian than CAS. The reasons for the poor outcomes of CAS in the octogenarian are unclear. The results of CAS in the older patient population are worrisome, and this 'less invasive' technique may prove to be an inferior alternative in this patient group
PMID: 12522696
ISSN: 0890-5096
CID: 48172
Transcatheter embolization of extremity vascular malformations: the long-term success of multiple interventions
Rockman, Caron B; Rosen, Robert J; Jacobowitz, Glenn R; Weiswasser, Jonathan; Hofstee, Dirk J; Fioole, B; Lamparello, Patrick J; Adelman, Mark A; Gagne, Paul J; Riles, Thomas S
Vascular malformations of the extremities present a difficult therapeutic challenge. Ligation of feeding vessels may lead to tissue necrosis and limb loss and can make subsequent attempts at transcatheter therapy impossible. The purpose of this study was to review our results with transcatheter embolization therapy in symptomatic vascular malformations in the upper and lower extremities in 50 patients. A retrospective review was conducted of a computerized database of all patients undergoing transcatheter therapy of peripheral vascular malformations at our institution. The mean age of the patients was 22 years (range 1-51 years), and 34% were male. The most common presenting symptoms included pain (80%), swelling (68%), ulceration or distal ischemia (18%), and hemorrhage (6%). Previous unsuccessful surgical treatment or embolization had been performed in 24% and 18% of patients, respectively. Predominantly venous lesions were treated by sclerotherapy with injection of ethanol. Arteriovenous and arterial lesions were treated by embolization via the arterial branch feeding vessels with cyanoacrylate. The most common vessels involved and treated were branches of the profunda femoris and tibial arteries (83% of lower extremity lesions), and branches of the brachial and radial arteries (82% of upper extremity lesions). Patients required a mean of 1.6 embolization procedures (range 1-5) over a mean period of 57 months. Sixteen patients (32%) underwent more than one embolization procedure. Of these, one was a planned staged procedure and 15 were performed secondary to residual or recurrent symptoms. Adjunctive surgical procedures were performed subsequent to embolization in three cases (6%). Ninety-two percent of patients remained asymptomatic or improved at a mean follow-up of 56 months. There was one case of limb loss (2%). Diffuse extremity vascular malformations are difficult to eradicate completely and recurrences are common. Although patients may require multiple embolization procedures and occasional adjunctive surgical resection, directed transcatheter embolization should be the treatment of choice for symptomatic extremity vascular malformations
PMID: 14670021
ISSN: 0890-5096
CID: 46294
A model for predicting occult carotid artery stenosis: screening is justified in a selected population
Jacobowitz, Glenn R; Rockman, Caron B; Gagne, Paul J; Adelman, Mark A; Lamparello, Patrick J; Landis, Ronnie; Riles, Thomas S
OBJECTIVES: The diagnosis and treatment of carotid artery disease is an integral part of stroke prevention. However, a population of patients who would benefit from screening for carotid artery stenosis has not been well defined. As part of an institutional stroke-screening program, a modified, rapid duplex scan was developed to evaluate patients for occult carotid stenosis. The goal of this study was to evaluate risk factors predictive of carotid stenosis in a selected population, and to identify patients who would benefit from carotid screening. METHODS: Patients were eligible for the study if they were >60 years of age and had a history of hypertension, heart disease, current smoking, or family history of stroke. A modified carotid duplex scan that had been previously validated against formal duplex scanning was utilized; this involved visualization of the carotid bulb and proximal internal carotid artery where Doppler flow velocities were obtained and recorded. RESULTS: Screening was performed on 394 patients. Thirty-eight patients (9.6%) had either unilateral or bilateral carotid stenosis of > or =50%. Risk factors evaluated included smoking, hypertension, cardiac disease, or hypercholesterolemia. If none of these risk factors was present, the incidence of carotid stenosis was 1.8%. This increased to 5.8% with one risk factor, 13.5% with two risk factors, and 16.7% with three risk factors. Two of three patients with all four risk factors had carotid stenosis (66.7%). Logistic regression and prespecified contrast statements for multiple comparisons were used to assess the relationship between the presence of risk factors and occult carotid artery stenosis. The presence of any one of these risk factors was associated with a statistically significant increase in the presence of occult carotid stenosis (P <.01). This was also statistically significant for the presence of any two risk factors (P <.01) or three risk factors (P <.05). CONCLUSION: The prevalence of carotid stenosis significantly increases with the presence of one or more identifiable demographic risk factors in a selected population. Assuming the diagnosis and treatment of carotid stenosis are fundamental to stroke prevention, screening for carotid artery disease is justified in this group of patients
PMID: 14560217
ISSN: 0741-5214
CID: 71130
Postoperative infection associated with polyester patch angioplasty after carotid endarterectomy
Rockman, Caron B; Su, William T; Domenig, Christopher; Lamparello, Patrick J; Adelman, Mark A; Jacobowitz, Glenn R; Pomposelli, Frank B; Riles, Thomas S
OBJECTIVES: Postoperative infection is one of the most dreaded complications associated with use of synthetic patches for carotid endarterectomy. Although polyester patches were used extensively for carotid patch angioplasty throughout the last decade, few reports detail cases of deep patch infection. We describe our experience with polyester patch infections after carotid endarterectomy.Patients and methods From January 1996 through December 2001 we treated polyester patch infections after carotid endarterectomy in 10 patients. RESULTS: The interval from primary carotid endarterectomy to presentation with infection ranged from 11 days to 30 months. All patients underwent repeat operation that involved tissue debridement, excision of the polyester patch, and either interposition grafting or patch angioplasty with autologous vein. No perioperative stroke or death occurred; however, 1 patient had transient hoarseness, and in 1 patient a pseudoaneurysm developed that required additional surgical repair with a saphenous vein interposition graft. All patients remain well and free of infection with follow-up as long as 56 months. CONCLUSIONS: Infection is a serious and rare complication of carotid patch angioplasty with polyester material. Nonetheless, it can be treated successfully with good results and acceptable morbidity with soft tissue debridement, prosthetic patch excision, and either patch angioplasty or interposition grafting with autologous vein
PMID: 12891105
ISSN: 0741-5214
CID: 71131
Endovascular abdominal aortic aneurysm (AAA) repair since the FDA approval. Are we going too far?
Adelman, M A; Rockman, C B; Lamparello, P J; Jacobowitz, G R; Tuerff, S; Gagne, P J; Nalbandian, M; Weisswasser, J; Landis, R; Rosen, R J; Riles, T S
BACKGROUND: Since the FDA approval of endovascular devices for abdominal aortic aneurysm (AAA) repair, clinicians have been relaxing the strict inclusion criteria of the clinical trials. We have reviewed our experience during and after the clinical trials to examine changes in patient selection, technical aspects of the procedure, and outcome. METHODS: A review of a prospectively compiled database of all endovascular AAA repairs performed at our institution was performed. RESULTS: Endovascular AAA repair was attempted in 130 patients: 46 (35.4%) as a part of clinical trials (Group I), and 84 (64.6%) since the FDA approval of the devices (Group II). Significant differences in patient selection included: a higher proportion of short (<15 mm) proximal necks in Group II (28.6 vs 0.0%, p<0.001), and a higher proportion of iliac occlusive disease in Group II (48.8 vs 15.4%, p=0.001). Additional trends suggested that Group II AAA's were more complex, including increased proximal neck angulation, increased proximal calcification, increased presence of proximal thrombus, and increased iliac tortuosity. Significant differences in technical aspects of the procedure included increased usage of iliac angioplasty (46.4 vs 13.3%, p<0.001), iliac stenting (31 vs 8.9%, p<0.01), and conduit access to the external iliac artery (10.7 vs 0%, p=0.03) in Group II. Analysis of outcome revealed a decreased incidence of the following in Group II cases: conversions to open repair (2.4 vs 10.9%), lower extremity ischemia (3.6 vs 13.0%), and graft limb occlusion (2.4 vs 8.7%). Other major perioperative complications did not differ significantly between the 2 groups. However, although the overall rate of any endoleak noted in the postoperative course was decreased in Group II cases (26.2 vs 32.6%), the incidence of proximal or distal attachment site leaks has increased (11.9 vs 4.3%, p=0.14). Although this comparison did not reach statistical significance, the magnitude of the increase is concerning. CONCLUSIONS: Although we have been able to offer endovascular AAA repair to a larger number of patients since FDA approval, endovascular management of increasingly complex proximal necks and increased iliac artery disease appears to have increased the incidence of attachment site endoleaks. Although many of these leaks have been successfully managed with adjunctive endovascular procedures, their increasing incidence is worrisome and suggests that we may need to re-evaluate current inclusion criteria for using this technology. Although difficult access issues have been handled with adjunctive procedures, the presence of a short, angulated proximal neck may be difficult to overcome, and may not be well suited for endovascular repair with the currently available devices
PMID: 12055568
ISSN: 0021-9509
CID: 32473
A reassessment of carotid endarterectomy in the face of contralateral carotid occlusion: surgical results in symptomatic and asymptomatic patients
Rockman, Caron B; Su, William; Lamparello, Patrick J; Adelman, Mark A; Jacobowitz, Glenn R; Gagne, Paul J; Landis, Ronnie; Riles, Thomas S
OBJECTIVE: Total occlusion of the contralateral internal carotid artery has often been considered to be a predictor of poor outcome after carotid endarterectomy (CEA) of ipsilateral carotid stenosis. Data from both the North American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid Atherosclerosis Study have suggested this to be true. However, each of these trials had relatively few patients with contralateral occlusion in the surgical arms of the studies. Recently, advocates of carotid angioplasty and stenting have suggested that this technique may be preferable in patients with a contralateral occlusion because of the perceived poor outcome with surgery. The purpose of this study was to review a large series of CEAs performed in patients with contralateral occlusion to see whether results differed from patients with patent contralateral arteries and to determine whether the presence of preoperative symptoms was an important factor in outcome in these cases. PATIENTS AND METHODS: A review was conducted of a prospectively compiled database of all primary CEAs performed at our institution from 1985 to 1999. Surgery was performed on 2420 patients, of whom 338 (14.0%) had contralateral total occlusion. RESULTS: Patients with contralateral total occlusion were more likely to be symptomatic (65.7% versus 60.1%; P =.1), male (70.9% versus 58%; P <.001), and hypertensive (63.9% versus 58.4%; P =.07) with a positive smoking history (42.6% versus 31.4%; P <.001) than patients with patent contralateral carotid artery. No significant difference was seen in the rates of perioperative neurologic events between patients with contralateral occlusion (3.0%) and those without (2.1%; P =.34). Among the total of 913 asymptomatic patients, of whom 115 had contralateral occlusion, no difference was seen in the rate of perioperative neurologic events (1.8% for contralateral occlusion cases; 1.9% for cases without contralateral occlusion). Among the total of 1507 symptomatic patients, of whom 223 had contralateral occlusion, no significant difference was seen in the rate of perioperative neurologic events (3.7% for contralateral occlusion cases; 2.2% for cases without contralateral occlusion; P =.2). CONCLUSION: The presence of contralateral occlusion does not appear to increase the perioperative risk of CEA. Although the risk of CEA in symptomatic patients with contralateral occlusion may be slightly increased, this must be weighed against the risk with medical treatment alone. CEA can be performed safely in patients with contralateral occlusion, which should not necessarily be considered a high-risk condition for surgery in favor of angioplasty and stenting
PMID: 12368723
ISSN: 0741-5214
CID: 71132
Aneurysm morphology as a predictor of endoleak following endovascular aortic aneurysm repair: do smaller aneurysm have better outcomes?
Rockman, Caron B; Lamparello, Patrick J; Adelman, Mark A; Jacobowitz, Glenn R; Therff, Sonya; Gagne, Paul J; Nalbandian, Matthew; Weiswasser, Jonathan; Landis, Ronnie; Rosen, Robert; Riles, Thomas S
Since the Food and Drug Administrations' approval of endovascular devices for abdominal aortic aneurysm (AAA) repair, clinicians have been relaxing the strict inclusion criteria present during the clinical trials. Although the long-term natural history of endoleaks remains unclear, attachment site leaks (type I) are believed to represent an ongoing risk for future rupture. We reviewed our experience with endovascular AAA repair to elucidate factors that predispose toward the development of endoleaks and found that larger AAAs are significantly more likely to have a short proximal neck and severe proximal angulation. These factors likely contribute to the significantly increased rate of type I endoleaks that occurred after endovascular repair of large AAAs. Small AAAs (<5) had the lowest rate of endoleaks overall (8.3%) and of type I endoleaks in particular (0%). We conclude that AAA size and morphology can be used to predict which aneurysms will experience attachment site endoleaks in their course; AAAs from 4.5 to 5 cm in diameter may be particularly well suited for endovascular repair in this regard
PMID: 12183772
ISSN: 0890-5096
CID: 71133
Are type II (branch vessel) endoleaks really benign?
Tuerff, Sonya N; Rockman, Caron B; Lamparello, Patrick J; Adelman, Mark A; Jacobowitz, Glenn R; Gagne, Paul J; Nalbandian, Matthew M; Weiswasser, Jonathan; Landis, Ronnie; Rosen, Robert J; Riles, Thomas S
The natural history and clinical significance of type II or branch vessel endoleaks following endovascular aortic aneurysm (AAA) repair remain unclear. Some investigators have suggested that these endoleaks have a benign course and outcome and that they can be safely observed. The purpose of this study was to document the natural history and outcome of all type II endoleaks that have occurred following endovascular AAA repair at our institution. A review of a prospectively compiled database of all endovascular AAA repairs performed at our institution was performed. From this review, we determined that type II endoleaks appear to have a relatively benign course, with a reasonable chance of spontaneously sealing within a 2-year period. No cases of rupture or aneurysm enlargement were documented in patients with open type II leaks. However, almost one-third of the patients did not manifest a type II leak until after their initial CT scan. The implications of such a 'delayed' leak are unclear. Careful follow-up remains mandatory in patients with type II endoleaks to better define outcome
PMID: 11904804
ISSN: 0890-5096
CID: 95785