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Role of apoptosis and proteolysis in the pathogenesis of iliac artery aneurysms
Jacob, Theresa; Hingorani, Anil; Ascher, Enrico
The objective of this study was to investigate the role of inflammation, programmed cell death, its molecular modulators, and proteolysis in the pathogenesis of iliac artery aneurysms (IAAs). Nineteen IAA specimens were obtained from patients undergoing elective surgical repair. All were males with ages ranging from 55 to 85 years (mean 73 years). Controls were iliac arteries (n=6) retrieved from surgical patients without aneurysmal disease. Standard histochemical techniques were used to assess elastic lamellae fragmentation and inflammatory infiltrate in aneurysmal and normal tissues Identification of different types of cells in the aneurysm wall and detection of death-pro molecules, Fas, p53, perforin, apoptosis-mediating bcl-2 family proteins, apoptotic death substrate, and poly(adenosine diphosphate-ribose) polymerase were performed immunohistochemically. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end-labeling (TUNEL) assay and caspase activity. Proteolytic activity was determined by 10% gelatin gel zymography. There is a conspicuous disruption and fragmentation of elastic lamellae in IAAs compared with normal arteries. Increased gelatinolytic activity was observed at 92, 72, and 67 kDa in the aneurysmal tissues. There was a significant loss of vascular smooth muscle cells (VSMCs) in the IAA walls compared with normal arteries (p < .02). Large numbers of inflammatory cells were observed in the IAA specimens (p = .01). Only aneurysmal arteries showed CD8+ T cells expressing death-promoting molecules. CD3+, CD8+, CD20+, CD30+, and CD68+ immunoreactive cells were significantly more prominent in the aneurysmal tissues than in the control arteries. There was a significant increase in the number of cells undergoing apoptosis in aneurysmal tissue than in the normal vessels (p < .02), as well as in the expression of bax, p53, CPP-32, and Fas. Apoptotic cells and proapoptotic molecules predominantly localized to the inflammatory infiltrate. VSMC apoptosis was significant in IAAs. The data confirm the architectural disruption of the IAA wall and illustrate an apparent biologic response involving inflammatory infiltrate, apoptosis, and signaling molecules capable of initiating cell death. In addition to compromising the mechanical integrity of the vessel wall, VSMC loss may contribute to imbalance in the protein profile, accelerating extracellular matrix degradation that could favor IAA development.
PMID: 15895673
ISSN: 1708-5381
CID: 2520562
Deep venous thrombosis after radiofrequency ablation of greater saphenous vein: a word of caution
Hingorani, Anil P; Ascher, Enrico; Markevich, Natalia; Schutzer, Richard W; Kallakuri, Sreedhar; Hou, Alexander; Nahata, Suresh; Yorkovich, William; Jacob, Theresa
PURPOSE: Radiofrequency ablation (RFA) of the greater saphenous vein (GSV; "closure") is a relatively new option for treatment of venous reflux. However, our initial enthusiasm for this minimally invasive technique has been tempered by our preliminary experience with its potentially lethal complication, deep venous thrombosis (DVT). METHODS: Seventy-three lower extremities were treated in 66 patients with GSV reflux, between April 2003 and February 2004. There were 48 (73%) female patients and 18 (27%) male patients, with ages ranging from 26 to 88 years (mean, 62 +/- 14 years). RFA was combined with stab avulsion of varicosities in 55 (75%) patients and subfascial ligation of perforator veins in 6 (8%) patients. An ATL HDI 5000 scanner with linear 7-4 MHz probe and the SonoCT feature was used for GSV mapping and procedure guidance in all procedures. GSV diameter determined the size of the RFA catheter used. Veins less than 8 mm in diameter were treated with a 6F catheter (n = 54); an 8F catheter was used for veins greater than 8 mm in diameter (n = 19). The GSV was cannulated at the knee level. The tip of the catheter was positioned within 1 cm of the origin of the inferior epigastric vein (first GSV tributary). All procedures were carried out according to manufacturer guidelines. RESULTS: All patients underwent venous duplex ultrasound scanning 2 to 30 days (mean, 10 +/- 6 days) after the procedure. The duplex scans documented occlusion of the GSV in 70 limbs (96%). In addition, DVT was found in 12 limbs (16%). Eleven patients (92%) had an extension of the occlusive clot filling the treated proximal GSV segment, with a floating tail beyond the patent inferior epigastric vein into the common femoral vein. Another patient developed acute occlusive clots in the calf muscle (gastrocnemius) veins. Eight patients were readmitted and received anticoagulation therapy. Four patients were treated with enoxaparin on an ambulatory basis. None of these patients had pulmonary embolism. Initially 3 patients with floating common femoral vein clots underwent inferior vena cava filter placement. Of the 19 limbs treated with the 8F RFA catheter, GSV clot extension developed in 5 (26%), compared with 7 of 54 (13%) limbs treated with the 6F RFA catheter (P =.3). No difference was found between the occurrence of DVT in patients who underwent the combined procedure (RFA and varicose vein excision) compared with patients who underwent GSV RFA alone (P =.7). No statistically significant differences were found in age or gender of patients with or without postoperative DVT (P = NS). CONCLUSION: Patients who underwent combined GSV RFA and varicose vein excision did not demonstrate a higher occurrence of postoperative DVT compared with patients who underwent RFA alone. Early postoperative duplex scans are essential, and should be mandatory in all patients undergoing RFA of the GSV.
PMID: 15337880
ISSN: 0741-5214
CID: 2520662
Duplex arteriography prior to femoral-popliteal reconstruction in claudicants: a proposal for a new shortened protocol
Ascher, Enrico; Markevich, Natalia; Schutzer, Richard W; Kallakuri, Sreedhar; Hou, Alexander; Nahata, Suresh; Yorkovich, William; Jacob, Theresa; Hingorani, Anil P
The standard preoperative duplex arteriography (DA) from the aorta to the pedal vessels is time consuming and may be unnecessary in patients presenting with calf claudication alone. The feasibility of a shortened protocol was evaluated. Of 286 femoral-popliteal reconstruction based on DA during the last 4A years, 79 (28%) were primary operations for calf claudication. Eliminating the aortoiliac portion of the test except for the distal external iliac artery and limiting the scanning of the infrapopliteal vessels to one or two arteries in the leg would significantly shorten the exam. To confirm the adequacy of the inflow tract, we relied on the common femoral artery Doppler waveform analysis and the intraoperative graft pressure upon completion of the bypass. Of the 79 primary femoral-popliteal bypasses, 53 (67%) had triphasic common femoral artery waveform and the remaining 26 had monophasic or biphasic waveforms. Three (6%) of the 53 femoral-popliteal bypasses in the former group had significant pressure gradients measured intraoperatively and were treated with iliac angioplasties and stents for unsuspected stenoses in 2 cases and a covered stent for a common iliac aneurysm in 1 case. Three, two, and one infrapopliteal vessel runoff was observed in 24 (45%), 16 (30%), and 9 (17%) extremities, respectively. Four patients (8%) had significant stenoses (>50%) or occlusion of all three infrapopliteal arteries. Eighty-one percent of the patients would have completed the short protocol had we scanned the peroneal artery initially. An additional 8% would have required scanning of a second vessel (anterior tibial) and only 11%, scanning of all three infrapopliteal vessels. The time interval for completion of short-protocol DA was significantly less than the time for the standard DA (16.2 A+/- 5.2A min vs. 35.1 A+/- 10.6 min) ( p < 0.01). We believe that the proposed short DA protocol combined with intraoperative graft pressure measurements can be used in 94% of the patients who have a patent popliteal artery (>/= 7 cm). It is a totally noninvasive approach that is particularly suitable for vascular technologists and surgeons who wish to start utilizing DA instead of contrast arteriography prior to infrainguinal reconstructions. However, the short protocol does not avert the need for completion arteriography of the inflow arteries and readiness to perform endovascular procedures to correct lesions not suspected by common femoral artery waveform analysis.
PMID: 15534733
ISSN: 0890-5096
CID: 2520632
Lower extremity deep venous thrombosis: vascular laboratory quality assurance without correlation between ultrasound and venography
Salles-Cunha, Sergio X; Ascher, Enrico; Hingorani, Anil; Markevich, Natalia; Yorkovich, William
Venography is rarely available for comparison with ultrasonography (US) as a means for quality assurance (QA) in the detection of lower extremity venous thrombosis. New QA methods must be implemented. We compared results of multiple serial studies performed in the same extremity as a QA indicator. From a 3-year sample of close to 9,000 venous tests, we obtained a subset of 44 patients who had 331 tests in 71 lower extremities throughout the years. A positive or negative study preceded or followed by another positive or negative study was considered as a confirmed study. A negative or positive study not preceded or followed by a negative or positive study was considered as unconfirmed. Explanations were then sought to explain unconfirmed results. There were 169 (51%) and 124 (37%) confirmed positive and negative studies, respectively, and 13 (4%) and 25 (8%) unconfirmed positive and negative studies, respectively. Of the 13 unconfirmed positive tests, 2 were preceded by negative tests, 3 were preceded and followed by negative tests, and 8 were followed by negative tests. Of these 13 tests, 4 documented extensive venous thrombosis. Of the 25 unconfirmed negative tests, 11 followed treatment for venous thrombosis, 6 had recurrent thrombosis with intermittent lysis, and 8 were followed by positive tests. Considering the low probability of extensive thrombosis being a false-positive test, positive predictive value was 95% (173/182). Excluding 11 negative tests following treatment for venous thrombosis, negative predictive value was 90% (124/138) and accuracy was 93% (297/320). US versus US and literature US versus venography comparisons of these statistics were similar.
PMID: 15490042
ISSN: 1538-5744
CID: 2520642
Role of duplex arteriography as the sole preoperative imaging modality prior to lower extremity revascularization surgery in diabetic and renal patients
Ascher, Enrico; Hingorani, Anil; Markevich, Natalia; Yorkovich, William; Schutzer, Richard; Hou, Alexander; Jacob, Theresa; Nahata, Suresh; Kallakuri, Sreedhar
The limitations and complications associated with contrast angiography (CA) prior to lower extremity revascularization have led to an increased interest in duplex arteriography (DA) as a potential replacement. We report our experience with DA in patients with diabetes and/or chronic renal insufficiency (CRI) that would particularly benefit from a noninvasive approach to preoperative evaluation of the arterial tree. From January 1998 to November 2000, DA was performed in 145 patients with diabetes mellitus and/or CRI prior to 180 arterial reconstructions. One hundred twenty-one procedures were performed on 91 patients with diabetes alone, 41 on 33 patients with diabetes and CRI, and 18 on 15 patients with CRI alone. Patient ages ranged from 36 to 98 years (mean 72 +/- 12 years). Indications for surgery were severe claudication in 33 (18%), rest pain in 37 (21%), nonhealing ischemic ulcers in 52 (29%), and limb gangrene in 58 (32%). Optimal inflow and outflow anastomotic sites were selected according to a diagram based on DA that included arterial tree imaging from mid-aorta to the pedal vessels. Preoperative contrast arteriography was performed in 16 cases (9%) because of extremely poor runoff based on DA and limited visualization of outflow vessels. The distal anastomosis was to the popliteal artery in 89 cases (49%) and to the tibial and pedal arteries in 91 (51%). Intraoperative findings confirmed the preoperative DA results with the exception of one (0.6%) where the distal anastomosis was placed proximal to a significant stenosis requiring an extension graft. The use of DA presents a safe and reliable option to prebypass CA for many patients with diabetes or CRI. The ease of use and favorable patient outcomes achieved by this imaging modality may rival the use of CA for these patients.
PMID: 15164264
ISSN: 0890-5096
CID: 2520682
A comparison of magnetic resonance angiography, contrast arteriography, and duplex arteriography for patients undergoing lower extremity revascularization
Hingorani, Anil; Ascher, Enrico; Markevich, Natalia; Kallakuri, Sreedhar; Schutzer, Richard; Yorkovich, William; Jacob, Theresa
The objective of this study was to compare magnetic resonance angiography (MRA), contrast arteriography (CA), and duplex arteriography (DA) for defining anatomic features relevant to performing lower extremity revascularizations. From March 1, 2001 to August 1, 2001, 33 consecutive inpatients with chronic lower extremity ischemia underwent CA, MRA, and DA before undergoing lower extremity revascularization procedures. The reports of these tests were compared prospectively and the differences in the aortoiliac segment, femoral-popliteal, and infrapopliteal segments were noted. The vessels were classified as mild disease (<50%), moderate disease (50-70%), severe disease (71-99%), and occluded. These studies and treatment plans based on these data were compared. During this time period, 11 patients were not able to undergo MRA and therefore were excluded from the study. Thirty-three patients were included in this study. These patients underwent 35 procedures, as 2 patients underwent bilateral procedures. The mean age of the 33 patients was 76+/-10 years (SD). Indications for the procedures included gangrene (20), ischemic ulcer (8), rest pain (4), and severe claudication (1). Patients' medical history included diabetes mellitus (25), hypertension (20), and end-stage renal disease (5). No differences were noted between intraoperative findings and CA in this series. Two of the three differences between DA and CA were felt to be clinically significant whereas 9 of the 12 differences between MRA and CA were felt to be clinically significant. On the basis of these data in this series, MRA does not yet seem to be able to obtain adequate data on infrapopliteal segments, at least not for this highly selected population. When severe tibial calcification or very low flow states are identified, CA may be necessary for patients undergoing DA.
PMID: 15354630
ISSN: 0890-5096
CID: 2520652
Magnetic resonance angiography versus duplex arteriography in patients undergoing lower extremity revascularization: which is the best replacement for contrast arteriography?
Hingorani, Anil; Ascher, Enrico; Markevich, Natalia; Kallakuri, Sreedhar; Hou, Alex; Schutzer, Richard; Yorkovich, William
OBJECTIVE: In an effort to explore alternatives to contrast material-enhanced arteriography, we compared magnetic resonance angiography (MRA) and duplex arteriography (DA) with contrast arteriography (CA) for defining anatomic features in patients undergoing lower extremity revascularization. METHODS: From August 1, 2001, to August 1, 2002, 61 consecutive inpatients (64 limbs) with chronic lower extremity ischemia underwent CA, MRA, and DA before undergoing lower extremity revascularization procedures. The reports of these tests and images were compared prospectively, and the differences in the iliac, femoropopliteal, and infrapopliteal segments were noted. The vessels were classified as mildly diseased (<50%), moderately diseased (50%-70%), severely diseased (71%-99%), or occluded. The studies and treatment plans based on these data were compared. RESULTS: Mean patient age was 76 +/- 10 years (SD). Indications for the procedures included gangrene (43%), ischemic ulcer (28%), rest pain (19%), severe claudication (9%), and failing bypass (1%). During this period 35 patients were ineligible for the protocol, because they could not undergo MRA (n=27) or angiography (n=8). Of the total 192 segments in the 64 patients (iliac, femoropopliteal, tibial), 17% were not able to be fully assessed with DA, and 7% with MRA. Disagreements with CA and DA were found in the iliac, femoropopliteal, and tibial segments in 0%, 7%, and 14% of cases, respectively, and between CA and MRA in 10%, 26%, and 42% of cases, respectively. Two of 9 differences (22%) between DA and CA were thought to be clinically significant, and 28 of 45 differences (62%) between MRA and CA were thought to be clinically significant. CONCLUSIONS: A review of the data obtained in this series indicates that MRA does not yet seem to yield adequate data, at least in this highly selected population at our institution. When severe calcification is identified, CA may be necessary in patients undergoing DA.
PMID: 15071431
ISSN: 0741-5214
CID: 2520692
The Dialysis Outcome and Quality Initiative (DOQI) recommendations
Ascher, Enrico; Hingorani, Anil
National surveys have demonstrated that the US End Stage Renal Disease (ESRD) program has witnessed an increasing number of patients each and every year with a corresponding increase in cost. However, when compared to the data from the ESRD program of other countries, we find that these US patients have a low rate of autogenous arteriovenous access (AVA) placement and increased use of nonautogenous (or prosthetic) AVA. Some of the impetus for this can be attributed to (1) the lack of adequate or easily identifiable superficial veins in patients starting on hemodialysis with a history of multiple venipuncture or obesity, (2) earlier access rates of nonautogenous AVA as compared to autogenous AVA, (3) the relative ease of placement of nonautogenous AVA, and (4) a prior payment differential in favor of nonautogenous AVA placement that has since been abolished. However, by virtue of the increased number of procedures required to maintain nonautogenous AVA patency when compared to that of autogenous AVA patency, hemodialysis access failure has become the most frequent cause of hospitalization among ESRD patients. To further investigate this issue, the National Kidney Foundation Dialysis Outcome and Quality Initiative (DOQI) organized multidisciplinary work groups who reviewed 3325 articles concerning various issues of ESRD over a 2-year period. They suggested that autogenous AVA have the best longer-term patency rates and require the fewest interventions as compared to other access types. In order to improve overall patency rates and help contain angioaccess costs, these DOQI recommendations were published in 1997 and updated in 2000. While there is evidence that the guidelines are slowly being adopted, there remains much room for improvement in their implementation.
PMID: 15011173
ISSN: 0895-7967
CID: 2520702
Intraoperative carotid artery duplex scanning in a modern series of 650 consecutive primary endarterectomy procedures
Ascher, Enrico; Markevich, Natalia; Kallakuri, Sreedhar; Schutzer, Richard W; Hingorani, Anil P
PURPOSE: Thromboembolic complications after carotid endarterectomy are frequently associated with technical defects. We analyzed the effect of intraoperative duplex scanning in detection of significant but clinically unsuspected technical defects and residual common carotid artery (CCA) disease as a potential source of postoperative transitory ischemic attack (TIA) and stroke. METHODS: From April 2000 to April 2003, 650 consecutive primary carotid endarterectomy procedures were performed in 590 patients at a single institution by two vascular surgeons. Patients included 335 men (57%) and 255 women (43%). Indications for surgery were asymptomatic internal carotid artery (ICA) stenosis (>or=70%) in 464 patients (71%). All procedures were performed with the patient under general anesthesia, with synthetic patch angioplasty in 644 (99.1%). Major technical defects at intraoperative duplex scanning (>30% luminal internal carotid artery stenosis, free-floating clot, dissection, arterial disruption with pseudoaneurysm) were repaired. CCA residual disease was reported as wall thickness (0.7-4.8 mm; mean, 1.7 +/- 0.7) and percent stenosis (16%-67%; mean, 32% +/- 8%) in all cases. Postoperative 30-day TIA, stroke, and death rates were analyzed. RESULTS: There were no clinically detectable postoperative thromboembolic events in this series. All 15 major defects (2.3%) identified with duplex scanning were successfully revised. These included 7 intimal flaps, 4 free-floating clots, 2 ICA stenoses, 1 ICA pseudoaneurysm, and 1 retrograde CCA dissection. Diameter reduction ranged from 40% to 90% (mean, 67 +/- 16%), and peak systolic velocity ranged from 69 to 497 cm/s (mean, 250 +/- 121 cm/s). Thirty-one patients (5%) with the highest residual wall thickness (>3mm) in the CCA and 19 (3%) with the highest CCA residual diameter reduction (>50%) did not have postoperative stroke or TIA. Overall postoperative stroke and mortality rates were 0.3% and 0.5%, respectively; combined stroke and mortality rate was 0.8%. One stroke was caused by hyperperfusion, and the other occurred as an extension of a previous cerebral infarct. No patients had TIAs. Two deaths were caused by myocardial infarction, and one death by respiratory insufficiency. CONCLUSION: We believe intraoperative duplex scanning had a major role in these improved results, because it enabled detection of clinically unsuspected significant lesions. Residual disease in the CCA does not seem to be a harbinger of stroke or TIA.
PMID: 14743146
ISSN: 0741-5214
CID: 2520712
Postoperative anticoagulation in vascular surgery--Part two: A summary of lessons learned in our successful discharge planning experience using enoxaparin after vascular surgery
Gramse, Carol Ann; Hingorani, Anil; Ascher, Enrico
Postoperative anticoagulation is not an uncommon scenario for patients undergoing vascular procedures. Additional postoperative length of stay (LOS) is necessary to achieve a therapeutic international normalized ratio with traditional protocols using unfractionated heparin. In part one of this 2-part article, low-molecular-weight heparin (LMWH), specifically enoxaparin, was shown to be a safe and effective alternative for anticoagulation after vascular surgical procedures. At the same time, its use can significantly reduce the average postoperative LOS after vascular procedures. This article describes a successful discharge planning experience using the LMWH enoxaparin after vascular procedures. We share our perspective on the role of the various members of the vascular surgical team as implemented in our acute care vascular surgical service clinical setting. Our discussion may offer ideas for consideration by vascular clinicians in their clinical settings.
PMID: 14652588
ISSN: 1062-0303
CID: 2520732