Search

Objective: this study was undertaken to examine and compare the effects of thrombus, thrombectomy, and thrombolysis on endothelial function as measured by endothelium-dependent vasorelaxation (EDR). Methods: adult, male New Zealand white rabbits underwent ligation of the left common iliac to femoral artery to induce thrombosis and were then randomly assigned to one of five groups, n=6 in each. Group A consisted of ligation and thrombosis for 4 h. Group B underwent similar ligation for 4 h, but without intraluminal thrombus present. Following 4 h of ligation and thrombosis, Group C underwent thrombectomy while group D was treated with urokinase (UK), 4000 U/min for 30 min. Group E underwent UK infusion alone. The right external iliac artery served as control vessel in each group. All arteries were removed and endothelial function was determined by measuring EDR. Results: the presence of thrombus reduced EDR by 50% (group A) compared to control. Vessels with interrupted flow, but not exposed to thrombus, retained normal EDR (group B). Thrombectomy decreased EDR significantly (group C) compared to thrombolysis (group D) and control. UK did not significantly alter EDR (groups D, E).Conclusions: exposure of endothelium to thrombus significantly decreases EDR. EDR was not affected by interruption of blood flow in the absence of thrombus. Thrombectomy appeared to cause a further additive insult to the endothelium. In contrast, thrombolysis with UK preserved residual endothelial function. These data suggest that it is important to differentiate the effects of thrombus on endothelium from effects due to thrombectomy or thrombolysis when evaluating treatment modalities for arterial thrombosis.

We report an unusual case of type IV Thoracoabdominal Aneurysm (TAA) with Superior Mesenteric Artery (SMA), celiac artery, and bilateral renal artery aneurysms in a patient who underwent an earlier repair of two infrarenal Abdominal Aortic Aneurysm (AAA) ruptures. Because of the presence of the visceral artery aneurysms and the earlier operation through the retroperitoneum, standard surgical treatment via a retroperitoneal approach with an inclusion grafting technique was considered difficult. A combined surgical approach achieving retrograde perfusion of all four visceral vessels and endovascular grafting allowing exclusion of the TAA was accomplished. Complete exclusion of the aneurysm and normal perfusion of the patient’s viscera was documented by means of follow-up examinations at 3 and 6 months. The repair of a type IV TAA with a Combined Endovascular and Surgical Approach (CESA) allowed us to manage both the aortic and visceral aneurysms without thoracotomy or re-do retroperitoneal exposure and minimized visceral ischemia time. If the durability of this approach is confirmed, it may represent an attractive alternative in patients with aneurysmal involvement of the visceral segment of the aorta. (J Vasc Surg 1999;30:555-60.)

Purpose. Hypertension (HTN), hyperlipidemia (HLP), and hyperinsulinemia are known risk factors for the development of cardiovascular disease. Each has independently been shown to be associated with impaired endothelial function, as demonstrated by decreased endothelial derived relaxation (EDR). Previous work in our laboratory has shown that rats fed a high-fat sucrose (HFS) diet will become insulin resistant, hypertriglyceridemic, and hypertensive. We hypothesize that the development of these diet-induced risk factors is associated with endothelial dysfunction and a significant decrease in EDR. Furthermore, the endothelial dysfunction will be improved by returning to a normal (low-fat complex carbohydrate (LFCC)) diet. Methods. Adult, male Fischer rats were fed either a LFCC or a HFS diet for 6 months (n = 8 in each group). A third group of rats (SWITCH) was fed a HFS diet for 6 months and then changed to a LFCC diet for 4 weeks. Blood pressure was measured via the tail-cuff method weekly. The rats were sacrificed and aortic ring segments were placed in physiologic tissue baths for measurement of vascular reactivity to various agents. Arterial ring segments were constricted with potassium chloride (K) and phenylephrine (PE). Endothelial-dependent vasorelaxation was measured with acetylcholine (Ach), bradykinin (BK), and calcium ionophore (CA). Endothelial-independent relaxation was measured using sodium nitroprusside (NTP). Results. The HFS diet group developed HTN compared to LFCC group. Vasoconstriction to K and PE were similar in all groups. Vasorelaxation to Ach, BK, and CA was significantly decreased in the HFS group, but returned to baseline in the diet-switched group, as did the systolic blood pressure. There were no differences in relaxation to NTP. Conclusions. HFS diet-induced HTN is associated with significantly decreased EDR. Switching to a low-fat diet reverses this effect. The vascular smooth muscle contraction and endothelial-independent relaxation are not affected by the diet-induced risk factors. There is a direct and reversible effect of an HFS diet on endothelial function and blood pressure.

Background The simulation and rehearsal of virtual endovascular procedures are anticipated to improve the outcomes of actual procedures. Contemporary, high-fidelity simulation is based on feedback systems that combine concepts of mechanical, electrical, computer, and control systems engineering to reproduce an interactive endovascular case. These sophisticated devices also include psychometric instruments for objective surgical skill assessment. The goal of this report is to identify the design characteristics of commercially available simulators for endovascular procedures and to provide a cross-section comparison across all devices to aid in the simulator selection process. Methods Data were obtained (1) by a standard questionnaire issued to four simulator companies prompting for relevant design details of each model for the expressed purpose of publication, (2) from each manufacturer's respective website including appended sales brochures and specification sheets, and (3) by an evaluation of peer-reviewed literature. Focus topics include haptic technology, vessel segmentation, physiologic feedback, performance feedback, and physical logistics (ie, weight, dimensions, and portability). All data sources were surveyed between January 1, 2012, and June 30, 2013. Results All of the commercially available, high-fidelity endovascular simulators use interactive virtual environments with preprogrammed physics and physiology models for accurate reproduction of surgical reality. The principal differences between devices are the number of access sites and haptic devices, the ability to reconstruct patient-specific anatomy for preprocedural rehearsal, and the available peripheral training modalities. Hardware and software options can also vary within the same device in comparing patient-specific with generic cases. Conclusions Despite our limited knowledge about the potential of high-fidelity simulation within the endovascular world, today's currently available simulators successfully provide high-fidelity reproductions of the endovascular environment. We have found that all of the commercially available devices incorporate the necessary features for a high-fidelity experience: (1) haptic technology, (2) vessel reconstruction, (3) physiology feedback, and (4) performance feedback. Significant variations in design do exist and may influence differences in skill development, evaluation, or cost. However, further validation of these differences is still needed and would benefit program directors interested in expanding these platforms for vascular training and certification as this technology matures.

Objectives Vascular grafts currently see limited use in small diameter applications due to the prevalence of thrombosis. Patency of ePTFE grafts could be improved by reducing thrombosis via an endothelial cell specific peptide fluorosurfactant polymer (FSP) coating. Methods In this study, ePTFE grafts were coated with cRRE-FSP, RGD-FSP, or Maltose-7 (M7)-FSP, sodded with porcine pulmonary artery endothelial cells (PPAECs), and evaluated in vivo in a porcine carotid artery interposition model. Grafts were excised after one month and evaluated by quantifying thrombosis and intimal hyperplasia and by qualitatively examining inflammation, smooth muscle cell infiltration, and endothelialization. Results Angiography of the grafts after one month showed at least partial patency in all grafts with the exception of one RGD-coated and one uncoated graft. Immunofluorescent staining of cell-sodded grafts showed a complete endothelial layer of adherent and spread PPAECs. Thrombus formation was present in two uncoated grafts and one RGD-coated graft. Intimal hyperplasia comprised mostly of smooth muscle cells was present in all grafts, but developed to the highest extent in RGD-coated grafts. Mean graft occlusion in M7 (24.7%) and cRRE-coated grafts (25.1%) was reduced by half compared to uncoated (58.5%) and RGD-coated grafts (53.9%). Conclusions Increased intimal hyperplasia in RGD grafts suggests that RGD, a prominent cell adhesion peptide, may facilitate ingrowth of more smooth muscle cells compared to the other grafts. These results show that cRRE-FSP coating of ePTFE grafts may reduce thrombosis, making it a promising candidate for improving graft patency.

The following case report describes using carbon dioxide (CO 2 ) as contrast media for intravascular optical coherence tomography (OCT) imaging in the superficial femoral artery. For initial OCT imaging, 20 mL of iodinated contrast was used during automated pullback. This was followed by 20 mL of hand-injected dextran 40 in normal saline, and finally hand-injected 50 mL of CO 2 . CO 2 gave comparable erythrocyte clearance and imaging quality compared with dextran and iodinated contrast. To our knowledge, this is the first reported case using both dextran and CO 2 with OCT imaging of the superficial femoral artery. Using CO 2 is a viable option in patients with contraindications to contrast or dextran use.

Hepatic lipase (HL) and lipoprotein lipase (LPL) are key enzymes involved in the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins. Despite their similarities, the role that each of these two lipases play in the metabolism of triglyceride-rich lipoproteins and high density lipoproteins is distinct. In order to identify structural domains that may confer the different substrate specificities between HL and LPL, we have utilized a novel approach for performing structure-function analysis of a protein, in vivo, by using recombinant adenovirus vectors to express native and mutant enzymes in an animal model for a human genetic deficiency. HL-deficient mice (n = 19) characterized by increased plasma cholesterol and phospholipid concentrations were injected with adenovirus expressing luciferase (rLucif-AdV), native hepatic (rHL-AdV), and lipoprotein lipase (rLPL-AdV) or lipase mutants in which the lid covering the catalytic site of either enzyme was exchanged (rHL+LPL lid-AdV and rLPL+HL lid-AdV). Mice injected with rLucif-AdV had no changes in post-heparin HL and LPL activities (217 +/- 29 and 7 +/- 2 nmol/min/ml, respectively) as well as plasma lipids. Despite expression of similar levels of post-heparin plasma lipase activity on day 5 post-adenovirus infusion (9806 +/- 915 and 9677 +/- 2033 nmol/min/ml, respectively) mice injected with rHL-AdV or rHL+LPL lid-AdV demonstrated marked differences in the reduction of plasma phospholipids (70% and 32%, respectively, p < 0.005). Similarly, despite post-heparin plasma lipolytic activities of 4495 +/- 534 and 4844 +/- 1336 nmol/min/ml, injection of rLPL-AdV or rLPL+HL lid-AdV resulted in phospholipid reductions of 31% and 81% (p < 0.005). Exchange of the lipase lid did not significantly alter plasma triglyceride concentrations. Thus, preferential in vivo hydrolysis of phospholipids was demonstrated in animals expressing lipases containing the HL lid but not the LPL lid. These studies identify the lipase lid as a major structural motif responsible for conferring the different in vivo phospholipase activities between HL and LPL, a function which may modulate the distinct physiological roles of these two similar lipolytic enzymes in lipoprotein metabolism. The use of recombinant adenovirus to express mutant proteins in animal models for human genetic deficiencies represents a powerful, new approach for performing structure-function analysis of proteins in vivo.

The objective of this study was to evaluate the potential for biomimetic self-assembling fluorosurfactant polymer (FSP) coatings incorporating heptamaltose (M7-FSP) to block nonspecific protein adsorption, the cell adhesive RGD peptide (RGD-FSP), or the endothelial cell-selective CRRETAWAC peptide (cRRE-FSP) to improve patency and endothelialization in small-diameter expanded polytetrafluoroethylene (ePTFE) vascular graft implants.ePTFE vascular grafts (4 mm in diameter, 5 cm in length) were coated with M7-FSP, RGD-FSP, or cRRE-FSP by dissolving FSPs in distilled water and flowing solution through the graft lumen for 24 hours. Coatings were confirmed by receding water contact angle measurements on the lumen surface. RGD-FSP and cRRE-FSP grafts were presodded in vitro with porcine pulmonary artery endothelial cells (PPAECs) using a custom-designed flow system. PPAEC coverage on the lumen surface was visualized with epifluorescent microscopy and quantified. Grafts were implanted as carotid artery interposition bypass grafts in seven pigs for 33 ± 2 days (ePTFE, n = 3; M7-FSP, n = 4; RGD-FSP, n = 3; cRRE-FSP, n = 4). Patency was confirmed immediately after implantation with duplex color flow ultrasound and at explantation with contrast-enhanced angiography. Grafts were sectioned for histology and stained: Movat pentachrome stain to outline vascular layers, immunofluorescent staining to identify endothelial cells (anti-von Willebrand factor antibody), and immunohistochemical staining to identify smooth muscle cells (anti-smooth muscle α-actin antibody). Neointima to lumen area ratio was determined to evaluate neointimal hyperplasia.Receding water contact angle measurements on graft luminal surfaces were significantly lower (P .05) on FSP-coated ePTFE surfaces (M7-FSP, 40 ± 16 degrees; RGD-FSP, 25 ± 10 degrees; cRRE-FSP, 33 ± 16 degrees) compared with uncoated ePTFE (126 ± 2 degrees), confirming presence of the FSP layer. In vitro sodding of PPAECs on RGD-FSP and cRRE-FSP grafts resulted in a confluent monolayer of PPAECs on the luminal surface, with a similar cell population on RGD-FSP (1200 ± 187 cells/mm(2)) and cRRE-FSP (1134 ± 153 cells/mm(2)) grafts. All grafts were patent immediately after implantation, and one of three uncoated, two of three RGD-FSP, two of four M7-FSP, and two of four cRRE-FSP grafts remained patent after 1 month. PPAEC coverage of the lumen surface was seen in all patent grafts. RGD-FSP grafts had a slightly higher neointima to lumen area ratio (0.53 ± 0.06) compared with uncoated (0.29 ± 0.15), M7-FSP (0.20 ± 0.15), or cRRE-FSP (0.17 ± 0.09) grafts.Biomimetic FSP-coated ePTFE grafts can be used successfully in vivo and have potential to support endothelialization. Grafts modified with the M7-FSP and cRRE-FSP showed lower intimal hyperplasia compared with RGD-FSP grafts.

In 2002, an estimated six million interventional cardiology and endovascular procedures were performed in the USA, and that number exceeded 10.5 million in 2009. In most of these procedures, the common femoral artery is used as the cardiac access site. For each of these cases, vascular access management is a critical aspect to determining a successful outcome without complications. For many decades, manual compression has been the “gold standard” for postprocedure vascular access management. With the development of endovascular procedures, larger sheaths and more intense anticoagulation measures are now routinely employed. These factors place greater demands on the safe performance of vascular access. In addition, many patients are likely to undergo repeated angiographic procedures over time, most frequently using the femoral artery as the vascular entry point. Site selection, puncture and closure must be optimized to avoid access site complications, primarily related to bleeding. Vascular Closure Devices (VCDs) were designed to decrease time to achieve hemostasis, as well as access site bleeding, thus permitting shorter time to patient ambulation, and increased patient comfort compared with manual compression.

Background The use of antiplatelet and antithrombotic agents after peripheral vascular interventions is a common clinical practice despite a lack of clear convincing evidence or accepted practice guidelines. The goal of this study was to assess surgeons’ prescribing practices after endovascular procedures for lower extremity arterial occlusive disease. Methods Attendees at a national vascular meeting were asked to complete a voluntary survey indicating their prescribing practices of antiplatelet/antithrombotic agents for the following procedures: iliac bare-metal stent, iliac covered stent, infrainguinal balloon angioplasty, infrainguinal bare-metal stent, infrainguinal covered stent, infrainguinal atherectomy, and lower extremity cryoplasty. The respondents were given choices of aspirin (ASA) alone, clopidogrel alone, ASA/clopidogrel combined, warfarin alone, or ASA/clopidogrel/warfarin combined. They were also asked to indicate their preferred length of treatment for each medication or combination of medications for each procedure: 1, 3, 6, or 12 months. Results There were 51 respondents (48 vascular surgeons and 3 vascular fellows) with an average of 11 ± 6.4 years of experience and practicing in a university hospital (48%), community hospital (44%), or combined university/Veterans A hospital (6%) setting. The majority of respondents (98%) prescribe an antiplatelet agent for patients with peripheral arterial disease using 81 mg of ASA preferentially. Most surgeons do not obtain genetic testing (i.e., cytochrome P450, polypeptide 19 [CYP2C19] polymorphism) for antiplatelet effectiveness. The most common antiplatelet/antithrombotic medication of choice after lower extremity endoluminal therapy was a combination of ASA/clopidogrel. However, the duration of medical treatment was variable, with a 1- to 3-month course being the most common. The use of the ASA/clopidogrel combination increased with further distal endovascular treatment and the placement of stents versus angioplasty. In the vast majority of ASA-only responses, ASA was administered for at least 12 months if not recommended for life. Although the majority of surgeons would recommend dual antiplatelet therapy (52–77%), there was no consensus regarding the duration of treatment. Conclusions The antiplatelet/antithrombotic prescribing practices of vascular surgeons after lower extremity endovascular procedures are highly variable. Multicenter randomized controlled trials are needed to define optimal treatment efficacy and define the much-needed practice guidelines.

A safe and effective insulin infusion algorithm that achieves rigorous intraoperative glycemic control in noncardiac surgery has yet to be formally characterized and evaluated. We therefore report the validation of the DeLit Trial insulin infusion algorithm.Patients scheduled for major noncardiac surgery were randomized to a target intraoperative blood glucose concentration of 4.4-6.1 mmoL·L(-1) (80-110 mg·dL(-1)) intensive group or 10-11.1 mmoL·L(-1) (180-200 mg·dL(-1)) conventional group. Glucose was managed with a dynamic intravenous insulin infusion algorithm. We compared the randomized groups on glucose time-weighted average (TWA), proportion of time spent within target, number of severe (2.2 mmoL·L(-1) or40 mg·dL(-1)) or moderate (2.8 mmoL·L(-1) or50 mg·dL(-1)) hypoglycemic episodes, and within-patient variability in glucose concentrations expressed as standard deviation from the patient mean.One hundred eighty-seven patients were assigned to intensive glucose control, and 177 patients were assigned to conventional glucose control. Median (lower quartile value [Q1], upper quartile value [Q3]) of intraoperative TWA for the intensive vs conventional groups was 6 [5.6, 6.7] mmoL·L(-1) vs 7.7 [6.9, 9.2] mmoL·L(-1), respectively; P0.001. The intensive group spent 49% (29, 71) of the time within target, substantially more time than the conventional group spent either within the intensive target or within its own target (both P0.001). The intensive group had slightly lower within-patient glucose variability than the conventional group (0.9 [0.7, 1.3] mmoL·L(-1) vs 1.3 [0.8, 1.8] mmoL·L(-1), respectively; P0.001). Three patients had moderate hypoglycemia (intensive group), but none experienced severe episodes.Tight intraoperative glucose control in noncardiac surgery can be maintained successfully without serious hypoglycemic episodes. (ClinicalTrials.gov number, NCT00433251).

Background The continued success of elective endovascular aneurysm repair (EVAR) has led to an extension of this technology to ruptured aortas. The purpose of this study was to evaluate our results of ruptured infrarenal aortic aneurysm (rAAA). Methods The treatment results of all patients who underwent repair of rAAAs between January 1990 and May 2008 were reviewed retrospectively. Comorbidities, intraoperative details, and postoperative complications were tabulated. EVAR and open repair were compared. Results Between January 1990 and May 2008, 160 patients underwent repair of rAAA. Of these, 32 (20%) underwent EVAR for rAAA; of 160 patients, 112 were considered to have free rupture (70%) and 48 had contained rupture (30%). The average Acute Physiology and Chronic Health Evaluation II score was 13.3 ± 6.7. The Kaplan–Meier survival rates at 30 days, 6 months, 1 year, and 5 years were 69% (62,77), 57% (50,65), 50% (43,59), and 25% (19,34), respectively, with no difference seen in EVAR group as compared with open surgery (p = 0.24). Intraoperative mortality was 5.6%, with no patient undergoing EVAR suffering an intraoperative death (p = 0.03). However, 30-day mortality was 31.9% with no difference between EVAR and open surgery (31.2% vs. 32%; p = 0.93) results. Multivariate analysis for 30-day mortality found renal insufficiency (RI) odds ratio (OR): 2.4 (1.1, 5.3), p = 0.04; hypotension OR: 2.4 (1.1, 5.3), p = 0.02; and cardiac arrest OR: 3.8 (1.1, 11.6, p = 0.03), were all associated with the greatest mortality. Of all predictors analyzed, multivariate analysis found preoperative RI OR: 2.32 (1.55, 3.47), p < 0.001, was the only independent predictor of decreased long-term survival. Conclusions Mortality rates for rAAA remain high. The use of EVAR for these procedures equals that for open repair with regard to 30-day and long-term mortality. Preoperative cardiac arrest and RI were associated with inferior results for both EVAR and open repair. Clinical judgment on when to use EVAR as a primary repair modality must be exercised.

BackgroundAcute limb ischemia (ALI) of the lower extremities remains a challenging clinical dilemma. Treatment of ALI has shifted toward endovascular therapies. The purpose of this study was to assess outcomes in patients treated for ALI with intra-arterial thrombolysis and/or adjuvant endovascular techniques.MethodsConsecutive patients with ALI of the lower extremities treated via endovascular intra-arterial methods between January 1, 2005 and September 30, 2007 were identified and reviewed. Comparisons of success, thrombolysis days, and all 30-day outcomes except mortality were performed using generalized estimating equations with logistic and proportional odds regression. Thirty-day mortality was assessed using logistic regression. Long-term patency, limb salvage, and survival were assessed using time-to-event methods, including Kaplan-Meier estimation and Cox proportional hazards models.ResultsThe analyzed dataset included 129 limbs treated in 119 patients presenting with ALI (class I 68%, class IIa 23%, class IIb 9%). The mean follow-up was 16.8 months (range: 0-43 months). Technical success was achieved in 82% cases. The 30-day mortality rate was 6.0% with all 30-day deaths occurring in females (P = .002). One (0.76%) central nervous system hemorrhage (CNS) was noted in this cohort. Primary patency for the entire cohort at 12 and 24 months was 50.1% (95% confidence interval [CI], 39.5-60.7) and 37.7% (95% CI, 26.2-49.1), respectively, while secondary patency was 74.0% (95% CI, 64.9-83.1) and 65.3% (95% CI, 54.5-76.2). Multivariable analyses identified patients presenting with femoropopliteal (hazard ratio [HR] 2.63) or tibial thrombosis (HR 2.80); graft thrombosis (vs native artery thrombosis, HR 2.57) and long-term dialysis (HR 3.66, 95% CI, 2.35-5.71, P < .001) were associated with poorer primary patency rates. Cumulative limb salvage at 24 months was 68.8% (95% CI: 59.5-78.1) with female gender (HR 3.34, P = .002) and thrombolysis ≥3 days (HR 2.35, P = .019) associated with an increased risk of limb loss. Overall 36-month survival was 84.5% (95% CI: 77.5-91.6). Women had decreased survival rates both in the short- and midterm (HR 6.29; 95% CI, 1.78-22.28; P = .004).ConclusionsEndovascular therapy with thrombolysis remains an effective treatment option for patients presenting with lower extremity ALI. Thrombolysis should be limited to

PURPOSE To review our experience with the endovascular treatment of chronic infrarenal aortic occlusion with regard to technical success and midterm patency, as well as perioperative mortality and morbidity. METHODS A retrospective review was performed of patients who presented from January 1, 2000, to December 31, 2005, with a diagnosis of chronic infrarenal aortic occlusion (TASC D) treated with endovascular techniques. In this time period, 31 patients (22 women; mean age 63 years) underwent attempted recanalization of the occluded aorta and iliac arteries. Claudication was the most common presenting symptom (14, 45%). Patients were treated solely with angioplasty and stenting or thrombolysis followed by angioplasty/stenting based on surgeon preference. RESULTS Technical success was 93%. The 2 failures were individual cases of wire-induced iliac artery perforation and failed access; both patients were treated with bypass grafting. Nine (29%) patients had thrombolysis prior to angioplasty. There were no perioperative deaths. Postoperative ankle-brachial indexes increased significantly from preoperative values (p

The aim of this study was to determine if significant differences in plaque composition exist between the popliteal and tibial vessels in patients with severe peripheral arterial disease (PAD). Forty-four patients with PAD required either above-knee (n = 38), below-knee (n = 5), or through-knee (n = 1) amputation for pedal sepsis/gangrene. The 51 vessels (anterior tibial, n = 9; posterior tibial, n = 10; peroneal, n = 3; popliteal, n = 29) were obtained and underwent intravascular ultrasound (IVUS) evaluation ex vivo within 24 hr of amputation. Sequential IVUS data were obtained at known intervals throughout the vessel length and then analyzed with radiofrequency techniques for quantification of plaque composition, plaque volume, and total vessel volume. Plaque composition was categorized as fibrous, fibro-fatty, necrotic core, and dense calcium. Clinical data were obtained via review of electronic records at the time of amputation. Two-sided t-tests were performed to compare components within each plaque. Results are expressed as mean percentage +/- standard error of the mean. Tibial vessels had more dense calcium within these plaques than popliteal arteries (33.8 +/- 5.6% vs. 10.6 +/- 1.9%, p < 0.001). Consequently, distal vessels had less fibro-fatty and fibrous plaque than popliteal arteries (7.7 +/- 1.4% vs. 13.1 +/- 1.2%, p < 0.005; 42.4 +/- 4.7% vs. 61.4 +/- 2.2%, p < 0.001, respectively). Necrotic core plaque composition was found to be similar when comparing tibial versus popliteal arteries (16.1% vs. 14.9%, p = nonsignificant). Clinical factors including diabetes, hyperlipidemia, and chronic renal insufficiency were not associated with plaque composition differences using a univariate analysis. As we progress distally in the arterial tree of patients with PAD, calcium plaque content increases with decreasing burden of fibro-fatty plaque. Clinical and demographic factors, with the exception of smoking, were not found to be associated with atherosclerotic plaque composition.

Purpose: To compare angiograms, considered the gold standard for diagnostic imaging of peripheral arterial disease (PAD), to the corresponding histological sections of popliteal and tibial vessels obtained after amputation to determine if angiography fails to define atheroma burden in “normal appearing” arteries in patients with PAD. Methods: Between 2004 and 2006, 69 patients underwent amputation of a lower extremity for severe tissue loss, gangrene, or pedal sepsis precluding limb salvage. Popliteal and tibial vessels were harvested, perfusion-fixed, and analyzed histologically. Thirty-four of these patients had pre-amputation angiography during attempted salvage procedures. Angiograms with patent or minimally diseased vessel segments (n = 19) were assessed for stenoses, diameter, and calcification by 3 vascular surgeons (n = 72 evaluations). These results were compared to corresponding cross-sectional histological slides (n = 66) in a blinded manner. Results: Angiograms performed prior to above-knee (n = 9) or below-knee (n = 10) amputation revealed 24 stenoses with a mean (±SD) diameter-reducing stenosis of 19.5%±15.2%. Corresponding histological cross sections revealed greater linear stenoses measured via boundaries of the internal elastic lamina (IEL stenosis, 28.9%±20.2%, p = 0.003 versus angiography) or via boundaries of the external elastic membrane (vessel stenosis, 43.1%±15.2%, p

IntroductionAcute arterial thrombosis causes endothelial dysfunction due to decreased nitric oxide bioactivity. Increased arginase activity may modulate intracellular L-arginine levels, the substrate for nitric oxide. The purpose of this study was to identify the role of arginase in endothelial dysfunction in cell culture and in the vasomotor response of arteries exposed to thrombus.MethodsRat aortic endothelial cells were exposed to thrombin at different time points. The cell extract was analyzed by immunoblotting and real-time polymerase chain reaction. Adult male rats underwent infrarenal aortic thrombosis by clip ligature for 1 hour. Infrarenal aortic ring segments were harvested and placed in physiologic buffer baths, and a force transducer was used to measure endothelial-dependent relaxation (EDR) and endothelial-independent relaxation (EIR). Arginase blockade was performed by incubating infrarenal aortic ring segments with arginase inhibitors for 1 hour before measuring EDR. Whole tissue extracts also underwent immunoblot analysis. The EDR and EIR curves were compared with analyses of variance.ResultsA 6.76 ± 1.4-fold induction in arginase I message levels (P = .001) was found in rat aortic endothelial cells exposed to thrombin (30 U/mL), and arginase I protein levels increased 2.1 times. The eight infrarenal aortic ring segments exposed to thrombosis for 1 hour had diminished EDR curves compared with 14 nonthrombosed normal segments (controls). The maximum (± SEM) EDR (acetylcholine 10−5M dose) in control infrarenal aortic ring segments was 108% ± 4.3% compared with 63% ± 6.2% for thrombosed infrarenal aortic ring segments (P < .001). Exposure to arterial thrombosis resulted in a 3.8-times increase in arginase I protein levels in infrarenal aortic ring segments. Preincubation of nine infrarenal aortic ring segments with the nonspecific (difluoromethylornithine) and six with specific ([S]-[2-boronoethyl]-L-Cysteine-HCl [BEC]) arginase inhibitor for 1 hour significantly increased the maximum EDR compared with untreated thrombosed segments (104 ± 5.2, 108 ± 7.6 vs 63% ± 6.2, P < .001). EDR curves for difluoromethylornithine- and BEC-treated infrarenal aortic ring segments were superimposed on control EDR curves. The EIR and the vasoconstriction with norepinephrine for all groups were similar.ConclusionEndothelial cells exposed to thrombin have increased arginase I messenger RNA and protein levels. Arterial thrombosis causes endothelial dysfunction without affecting smooth muscle responsiveness. Arginase blockade can lead to normalization of arterial vasomotor function.Clinical relevanceAcute arterial thrombosis may lead to endothelial dysfunction, manifested clinically by vasospasm and rethrombosis after initially successful thrombectomy or thrombolysis. We have identified that the key enzyme, arginase, which modulates levels of the nitric oxide precursor, L-arginine, is increased in arterial thrombosis. Thrombin, a component of thrombus, increases arginase levels, which may lead to decreased nitric oxide bioavailability. These studies indicate that arginase blockade restores endothelial function in arteries exposed to thrombosis. This work may lead to therapeutic alternatives including L-arginine supplementation or arginase blockade for patients with acute ischemia.

ObjectiveOcular symptoms and signs often herald hemispheric neurological events associated with extracranial cerebrovascular disease. However, the presence of a Hollenhorst plaque (HP) or retinal artery occlusion (RAO) and the risk of stroke is unclear. The purpose of this study was to review the outcomes of all patients who presented with a HP or RAO at a single institution.MethodsBetween 2000 and 2005, the management and outcome of 130 consecutive patients with a diagnosis of HP, central RAO, or branch RAO (ICD-9 codes 362.30 to 362.33) were reviewed. Patients with transient monocular visual loss (amaurosis fugax), retinal venous occlusion, and other ocular pathologies were excluded. Electronic and hardcopy medical records were reviewed for demographic data, clinical variables, radiological, and noninvasive vascular lab testing. Duplex and magnetic resonance angiography (MRA) of the carotid arteries were reviewed to confirm the presence of a lesion and quantify the degree of stenosis.ResultsDuring the study interval, 70 males and 60 females, with a mean age of 68 ± 16 (±SD) years underwent ophthalmologic evaluation. Symptoms were present in 61% of patients and included eye pain, blurred vision, or atypical visual symptoms, while 39% were asymptomatic. Atherosclerotic risk factors in this population included the presence of hypertension (73%), diabetes (33%), hyperlipidemia (75%), and tobacco use (38%). A majority of patients underwent carotid interrogation via Duplex imaging (68%). Carotid bifurcation stenoses ipsilateral to the ocular findings were 60% in only 8% of patients. Six patients with lesions greater than 60% went on to have either a carotid endarterectomy or carotid stenting. Follow-up data on this group ranged from 1 to 49 months (median, 22 months), with no stroke or transient ischemic attack identified. There were five deaths during follow-up; none related to stroke. Serial carotid Duplex examinations failed to identify progression of carotid stenoses in this group of patients. Overall survival was 94% at 36 months for this cohort.ConclusionThe presence of a HP or RAO is associated with a low prevalence of extracranial cerebrovascular disease that requires intervention. Furthermore, in contradistinction to amaurosis fugax, these ocular findings are not associated with a high risk for hemispheric neurological events.

PurposePercutaneous angioplasty and stenting (PTAS) is emerging as a therapeutic option for patients with chronic mesenteric ischemia. This study evaluated patency and mortality, and their relationship between degree of vessel occlusion (stenotic or totally occluded), stent characteristics, and comorbidities in patients who were treated with PTAS of the visceral vessels for chronic mesenteric ischemia.MethodsA retrospective review was performed of the records of all patients who underwent PTAS of the celiac, superior mesenteric, or inferior mesenteric arteries, or both, for symptomatic chronic mesenteric ischemia between January 2001 and December 2005. Patient demographics, lesion characteristics (stenosis or occlusion), interventional details, and early and late mortality rates were recorded. Cumulative mortality and patency rates and factors associated with outcomes were determined using Kaplan-Meier method and Cox proportional hazards modeling.ResultsEighty-seven mesenteric vessels (57 superior mesenteric, 23 celiac, and 7 inferior mesenteric arteries) were treated in 65 patients (29 men and 36 women). Completely occluded vessels were treated in 18 patients (28%), and >60% stenosis was treated in 47 patients (72%). Mesenteric angina was the most common symptom (97%). For the entire series, the cumulative 1-year results were primary patency, 65% (95% confidence interval [CI], 50%-80%); primary assisted patency, 97% (95% CI, 92%-100%); secondary patency, 99% (95% CI, 96%-100%); and survival, 89% (95% CI, 80%-98%). All deaths occurred ≤60 days after treatment. The endovascular treatment of visceral artery occlusion was not associated with diminished patency or survival, irrespective of stent size or number. Patients requiring bowel resection were less likely to survive than those who did not (odds ratio [OR], 26; 95% CI, 3.5-192; P < .001). One-year primary patency was worse among patients with chronic obstructive pulmonary disease (OR, 3.2; 95% CI, 1.4-7.7; P = .009) or who had femoral access (OR, 3.0; 95% CI, 1.1-7.9; P = .015).ConclusionsFor patients with chronic mesenteric ischemia, the results of endovascular treatment of occluded mesenteric arteries are indistinguishable from those treated for stenotic vessels. Patients requiring bowel resection are less likely to survive, and those with chronic obstructive pulmonary disease or who had femoral access have higher reintervention rates.

Objectives: Direct iliac access with or without conduit can be used in endovascular abdominal aortic aneurysm repair (EVAR) when anatomy is unfavorable for femoral access. The impact of this technical approach has not been adequately studied. We evaluated the perioperative outcomes in patients who required direct iliac access or conduit for EVAR and compared it with those who did not. Methods: Patients undergoing EVAR with and without iliac access/conduits were identified in the 2005 to 2012 National Surgical Quality Improvement Program data sets. Perioperative morbidity and mortality were assessed by 5:1 propensity matched (on age, gender, functional status, comorbidities, urgency, anesthesia use and relative operative duration) groups and multivariable analyses. Results: There were 15,082 patients undergoing infrarenal EVAR with 147 (1%) with (41) and without (107) conduit placement. Patients treated with iliac conduit/access were more likely to be female (25.9% vs 17.8%, P 1⁄4 .02) and have peripheral arterial disease (12.9% vs 5.5%, P < .01). There was no difference in age (74.5 6 8.4 conduit vs 74.9 6 8). On multivariate analysis the iliac conduits/access group had higher mortality (odds ratio [OR] 2.7; 95% confidence interval [CI], 1.4-5.4; P # .01), major complications, including cardiac arrest/ myocardial infarction (OR, 2.9; 95% CI, 1.3-6.3; P # .01) and pulmonary complications (OR, 2.1; 95% CI, 1.2-3.9; P 1⁄4 .01), and postoperative length of stay (means ratio, 1.3; 95% CI, 1.1-1.4; P # .01). No difference was noted for renal and wound complications. Matched analysis based on demographics, comorbidities, and operative time showed that iliac conduit/access patients had higher perioperative mortality (6.8% vs 2.3%, P < .01), cardiac (4.8% vs 1%, P < .01), pulmonary (8.8% vs 3.4%), and bleeding complications (10.2% vs 4.6%, P 1⁄4 .02). Conclusions: Our results demonstrate that the use of direct iliac access or conduits in EVAR is associated with increased mortality and major morbidity. In situations where anatomy mandates the use iliac access, surgeons should consider other options, including using lower profile devices or open aneurysm repair.

To examine the efficacy of a staged approach for the treatment of thoracoabdominal aneurysms, with open visceral revascularization followed by aortic endografting, in selected patients not considered candidates for conventional surgical repair.A retrospective review was conducted of 13 consecutive patients (8 women; mean age 64 years, range 33-77) who underwent visceral bypass followed by endovascular thoracoabdominal stent-graft implantation since 1999. Three patients presented with symptomatic aneurysms and 2 with rupture. Two patients had connective tissue disorders. All patients were deemed unfit for conventional thoracoabdominal repair due to comorbid conditions. The procedures were tailored to the pathology and specific patient anatomical situation: 5 aortic dissections with aneurysmal degeneration and 8 aneurysms (5 Crawford type II, 2 type III, and 1 type IV).The patients underwent retrograde visceral bypass (11 iliovisceral and 2 infrarenal aortic to visceral artery) followed by endovascular aortic relining with Zenith TX2 devices (n=7), homemade endografts (n=5), or a Talent thoracic endograft (n=1). Six patients required either a proximal or distal direct aortic repair (2 infrarenal reconstructions, 3 arch elephant trunk grafts, and 1 ascending aortic repair), while 3 patients also underwent left carotid-subclavian bypass grafting. Two patients developed paraplegia (1 following a ruptured aneurysm), and 2 patients had transient paraparetic events. Two patients had acute renal failure requiring short-term dialysis. Three patients died within 30 days; 2 late aneurysm-related deaths were noted. Three patients developed endoleaks during follow-up. Mean lengths of stay were 13 days (7-30) for the visceral bypass and 12 (3-25) for the endovascular stent-graft. In addition, remaining procedures in 8 patients required a mean of 7 days (0-14) in hospital.Staged endovascular and open procedures are feasible for thoracoabdominal aneurysms in patients at prohibitive risk for open thoracoabdominal reconstruction. However, this approach still carries a significant risk of perioperative mortality and morbidity. The potential for less invasive alternatives should be investigated.

Earlier observations implicate arterial thrombosis causing endothelial dysfunction by decreasing nitric oxide (NO) levels. NO levels are restored by regional L-arginine supplementation in animal models. The purpose of this study was to investigate the roles of thrombus components in NO generation.Human umbilical vein endothelial cells were harvested and cultured. The thrombus components thrombin, thrombin receptor agonist peptide (TRAP), and fibrin were added to a media of confluent human umbilical vein endothelial cells. Endothelial nitric oxide synthase (eNOS) activity was assayed by measuring conversion of L-arginine to L-citrulline. Endothelial NOS mRNA levels were quantitated using real-time polymerase chain reaction. Cellular membrane transport of L-arginine through the y+ channel was assayed with (14)C-labeled L-arginine. Arginase activity was determined as the conversion of (14)C L-arginine to (14)C urea and trapped as Na(2)(14)CO(3) for scintillation counting. Arginase protein amounts were assessed using Western blotting.Endothelial cells exposed to thrombin for 4 hours led to increased arginase activity. Thrombin (10 U/mL) caused a 1.6-fold increase compared with that in controls (320+/-29 microM urea/min versus 194+/-10 microM urea/min, p=0.03), and thrombin (30 U/mL) increased arginase activity 2.1-fold (398+/-27 microM urea/min, p0.001, versus controls); thrombin at 1 U/mL and fibrin had no effect. TRAP (50 microM) had an effect similar to that of thrombin 10 U/mL (316+/-21 microM urea/min, p0.01, versus controls). Protein amounts of arginase corresponded with activity levels. Neither eNOS nor inducible nitric oxide synthase (iNOS) activities were affected by exposure to thrombin and TRAP for 4 hours. Similarly, quantification of eNOS, iNOS, and endothelin-1 mRNA did not change, although CL-100, a known thrombin-inducible gene, was upregulated. Finally, transport of L-arginine into endothelial cells was unaffected by thrombin, TRAP, and fibrin exposure.Endothelial cells exposed to thrombin have increased arginase enzymatic activity, and the remainder of NO generation capability is unaffected. L-arginine supplementation or arginase blockade may counteract endothelial dysfunction in the setting of acute arterial thrombosis.

BACKGROUND Endothelial dysfunction is presumed to occur after hemorrhagic shock and resuscitation. This study uses a novel large-animal model to evaluate the effects of diverse resuscitation regimens on endothelial function. METHODS Twenty-seven adult domestic pigs (Sus scrofa) were used in this study. Control pigs (n = 3) underwent instrumentation alone. The remaining pigs experienced controlled hemorrhagic shock to a mean arterial blood pressure of 30 +/- 5 mm Hg for 45 minutes. Pigs were resuscitated to their baseline mean arterial blood pressure +/-5 mm Hg with either shed blood (SB; n = 8), lactated Ringers solution (40 mL/kg) followed by shed blood (LRSB; n = 8), or lactated Ringers solution alone (LR; n = 8). At baseline, 1 and 4 hours after resuscitation, acetylcholine (5, 10, and 15 microg/min) was infused into the proximal iliac artery to measure endothelial dependent relaxation (EDR). Sodium nitroprusside was infused to determine endothelial independent relaxation at the end of the study to insure smooth muscle vasomotor integrity. External iliac artery luminal diameter was measured using motion-mode ultrasonography. Statistical analysis was performed using repeated-measures analysis of variance with Tukey's post-hoc analysis. RESULTS All pigs survived the experiment. Pigs required ninefold more resuscitation with LR (370.58 +/- 29 mL/kg) versus SB (41.45 +/- 3.5 mL/kg) or LRSB (76.4 +/- 1.1 mL/kg) (p < 0.05). EDR for LR pigs 1 hour after initiation of resuscitation (R1) was 70.4 +/- 14.4% compared with 94.2 +/- 13.4% for SB and 106.1 +/- 8.2% for LRSB (p < 0.05). At 4 hours after resuscitation (R4), systolic luminal diameters were larger in the SB (0.45 +/- 0.01 cm) and LRSB (0.51 +/- 0.02 cm) groups compared with LR (0.41 +/- 0.03 cm) (LRSB versus LR; p = 0.01). At R4, EDR for the LR group was 78.3 +/- 10.7% compared with SB (101.4 +/- 8.3%) and LRSB (106.4 +/- 7.4%) (p < 0.05). Infusion of sodium nitroprusside confirmed integrity of smooth muscle vasorelaxation. Analysis of serum nitric oxide levels revealed decreased values after resuscitation with LR (9.44 +/- 0.76 mol/L) compared with SB (26.3 +/- 7.8 mol/L) and LRSB (16.3 +/- 1.0 mol/L) (p = not significant). CONCLUSION This is the first description of a large-animal model to evaluate EDR after hemorrhagic shock. Resuscitation with LR requires significantly larger volumes than SB or LRSB. LR resuscitation leads to endothelial dysfunction, as determined by decreased EDR, versus SB or LRSB. Resuscitation with blood products may preserve nitric oxide bioactivity when compared with crystalloid resuscitation in the setting of hemorrhagic shock.

Carotid stenosis after neck irradiation is a well-described entity. A 78-year-old man presented with left eye amaurosis fugax 11 years after radical neck dissection and neck irradiation for mucoepidermoid carcinoma. The patient underwent carotid artery stenting for a high-grade stenosis of the left internal carotid artery. Twenty months after the procedure, a pulsatile neck mass developed with intermittent arterial bleeding. After control of the bleeding, he underwent resection of the left carotid bifurcation, including the indwelling stent and reconstruction with a saphenous vein interposition graft. A pectoralis myocutaneous flap was used for wound closure. In this case, localized infection of the stented carotid artery led to mycotic degeneration, pseudoaneurysm formation, and erosion to the skin surface. As carotid artery stenting becomes more widely used, previously unreported late complications associated with this procedure are likely to become apparent, and continued close follow-up is warranted.

l Purpose: To investigate if a decrease in internal carotid artery (ICA) blood flow occurs with bilateral brachial artery occlusion (BBO), which may improve the effectiveness of cerebral protection devices during carotid interventions. Methods: Thirty-two asymptomatic patients (21 men; mean age 67 years) with carotid atherosclerosis between 15% and 79% were enrolled in the study. Carotid duplex ultra- sound was followed by volume flow rate (VF) determination in the right ICA, external carotid (ECA), and vertebral arteries. After baseline values were obtained, BBO was in- duced by bilateral arm pressure cuff inflation to 30 mmHg over the systolic pressure for no more than 3 minutes. VF measurements were repeated. Results: Seventeen patients (responders) had an ICA VF decrease from 4066109 mL/min (6SD) to 303690 mL/min (p50.005), while 15 patients (nonresponders) had no significant change in their ICA VF (3406192 versus 4476267 mL/min, p50.22). In responders, ECA VF increased (190665 to 2326125 mL/min), as did vertebral VF (77653 to 95660 mL/min; p.0.05). The ratio of ICA/ECA VF dropped from 2.13 to 1.31 in responders, but did not change in nonresponders. No patient exhibited any neurological symptoms during the study. Post cuff volume flows approximated baseline values. Cerebral magnetic resonance angiograms obtained in 10 responders revealed a complete circle of Willis in 8 (80%), while only 1 (16%) of 6 nonresponders had a complete pathway. Conclusions: A transient decrease in ICA VF, with concomitant elevations of the ECA and vertebral VFs, occurs with occlusion of the brachial arteries in the setting of a complete circle of Willis. Since no flow reversal occurs, this maneuver is insufficient to provide complete cerebral protection, but it may improve the effectiveness of cerebral protection devices and serve as an adjunctive maneuver in selected cases. Furthermore, changes in ICA VF may prove to be a noninvasive test for evaluating the integrity of the circle of Willis. J Endovasc Ther 2005;12:454-460

Objective The preferential use of endovascular techniques to treat complex aortoiliac disease has increased in recent years. The purpose of this study was to review the outcomes and durability of recanalization, percutaneous transluminal angioplasty, and stenting for iliac occlusions based on the patient's TransAtlantic Inter-Society Consensus (TASC) stratification. Methods Between 1998 and 2004, more than 628 patients with a clinical diagnosis of aortoiliac atherosclerotic disease underwent arteriography. The endovascular treatment of 89 consecutive patients (mean age, 66 years; 58% male) with symptomatic iliac occlusions (TASC-B, -C, and -D) was the basis for this study. Original angiographic imaging was evaluated for lesion grade and runoff. Electronic and hard copy medical records were reviewed for demographic data, clinical variables, and noninvasive vascular laboratory testing. Kaplan-Meier estimators were used to determine patency rates according to Society for Vascular Surgery criteria. Univariate and multivariate analyses were performed. P values of Results Recanalization and percutaneous transluminal angioplasty/stenting (total, 178 stents) of occluded iliac arteries was technically successful in 84 (91%) of 92 procedures. Patients in the TASC-C and -D groups often required multiple access sites (50%) and femoral artery endarterectomy/patch angioplasty for diffuse disease (24%). The mean ankle-brachial index increased from 0.45 to 0.83. Distal embolization led to major amputation and eventual death in one patient. Two other deaths occurred in the perioperative period secondary to cardiorespiratory causes. Three-year primary patency, secondary patency, and limb salvage rates were 76%, 90%, and 97%, respectively, and progression of infrainguinal disease led to late limb loss in two patients. Diabetes as a risk factor was significantly associated with decreased primary patency (57% vs 83%; P = .049). Critical ischemia at presentation was associated with decreased patency rates as well (P = .002), but TASC classification did not significantly alter patency rates. Conclusions Complex long-segment and bilateral iliac occlusions can be safely treated via endovascular means with high rates of symptom resolution. Initial technical success, low morbidity, and mid-term durability are comparable to results with open reconstruction. A liberal posture to open femoral artery reconstruction extends the ability to treat diffuse TASC-C and -D lesions via endovascular means.

The use of prosthetic conduits for lower extremity revascularization in the infrapopliteal location remains controversial. The objective of this report is to describe the immediate and long-term results in a series collected over two decades. Of the approximately 1,500 lower extremity revascularizations performed between 1978 and 1998, 81 infrapopliteal bypass cases using polytetrafluoroethylene (PTFE) as conduit in 77 patients were identified. Autogenous conduit was unavailable (86%) due to prior surgery: coronary artery bypass graft (25%), femoro-popliteal bypass (60%), or femoro-distal bypass (23%). All cases were done for critical ischemia using PTFE (6 mm, 95%; ring reinforced, 54%) under general (75%) or regional (25%) anesthesia. The distal anastomosis was to the anterior tibial artery (43%), posterior tibial artery (28%), tibioperoneal trunk (16%), or peroneal artery (12%), and vein patch was used in 25% of cases. Postoperative features included acute graft thrombosis in 11 cases (14%), all done under general anesthesia, perioperative death in 3 (4%), and a mean in-hospital stay of 17 days. Long-term follow-up has ranged from 1 to 144 months (mean, 22 months). At 36 months, primary patency was 20%, secondary patency 42%, and limb salvage 55% calculated by the Kaplan-Meier method. Univariate analyses revealed regional anesthesia was associated with prolonged primary patency (35% vs 15%, p = 0.026) while the use of ringreinforced PTFE conduit was associated with prolonged limb salvage (65% vs 40%, p = 0.042). All other variables including gender, smoking, diabetes mellitus, renal failure, decade of operation, use of vein patch or postoperative warfarin were not significantly associated with either prolonged patency or limb salvage. Despite poor primary patency, distal prosthetic bypass can lead to long-term limb salvage. These data suggest distal anastomotic vein patches and postoperative anticoagulation may not be beneficial adjuncts. However, the use of regional anesthesia may decrease the incidence of perioperative thrombosis and the use of ring reinforced conduit may prolong limb salvage.

The purpose of this study was to determine if a hemoglobin-based oxygen carrier, HBOC-201 (Hemopure, Biopure Corp), alters endothelial function and nitric oxide physiology when used for hemorrhagic shock.Female swine (Sus scrofa) underwent catheterization of the femoral, circumflex iliac, and pulmonary arteries. Control animals (n = 3) underwent instrumentation only. Study animals underwent hemorrhage to mean arterial pressure of 30 +/- 5 mmHg, were maintained for 45 minutes, and resuscitated to the baseline mean arterial pressure for 4 hours. Resuscitation fluids included: shed blood (SB) (n = 8), lactated Ringers plus shed blood (LRSB) (n = 8), and HBOC (n = 8). At baseline, 1, and 4 hours after resuscitation, acetylcholine was infused into the proximal iliac artery and endothelial-dependent relaxation was measured with M-mode ultrasonography. Nitric oxide levels were determined using a chemiluminescent assay.HBOC, SB, and LRSB provided equivalent survival and resuscitation as measured by mean arterial pressures (65.3 +/- 2.48 mmHg); pulmonary artery mean pressures (15.8 +/- 0.84 mmHg); and lactate levels (1.22 +/- 0.19 mmol/L). HBOC group animals required the lowest resuscitation volume (SB, 41.5 +/- 3.5 mL/kg; LRSB, 76.4 +/- 1.1 mL/kg, HBOC, 14.6 +/- 2.1 mL/kg, p0.001). Response to acetylcholine was normal in the SB and LRSB groups, but the HBOC group had diminished acetylcholine response (29.5% endothelial-dependent relaxation end resuscitation, p0.001). Arterial nitric oxide levels did not differ between study groups (p = 0.69).HBOC might be an alternative resuscitation agent in patients with hemorrhagic shock. Resuscitation with HBOC requires less volume than blood or crystalloid. These data suggest HBOC-201 has a vasoconstrictive effect that cannot be attributed soley to nitric oxide scavenging.

Background: The ideal resuscitation fluid for military applications would be effective at low volumes, thereby reducing logistical constraints. We have previously shown that the bovine hemoglobin-based oxygen carrier HBOC-201 is an effective low-volume resuscitation fluid. The goal of this experiment was to evaluate the effectiveness of HBOC-201 in comparison with other low-volume resuscitation fluids in a swine model of controlled hemorrhagic shock. Methods: Forty-two immature female Yorkshire swine (55-70 kg) were divided into seven groups of six. Animals were hemorrhaged to a mean arterial pressure of 30 mm Hg. After 45 minutes, animals were resuscitated to a mean arterial pressure of 60 mm Hg with one of the following agents: hypertonic saline 7.5% (HTS), hypertonic saline 7.5%/Dextran-70 6% (HSD), pentastarch 6%, hetastarch 6%, or HBOC-201. Lactated Ringer's (LR) solution was used as a standard resuscitation control. Another group of animals received no resuscitation. Resuscitation was continued for 4 hours. Hemodynamic variables and oxygen consumption were measured continuously. Arterial and mixed venous blood gases and serum lactate levels were measured at intervals throughout the experiment. Data were analyzed using analysis of variance with Tukey's post hoc test when appropriate. Significance was defined as p < 0.05. Results: Five of six animals in the no-resuscitation control group, six of six in the HTS group, and one animal in the HSD group died before completion of the study. All other animals survived to completion. Animals receiving resuscitation with HBOC-201 had significantly lower cardiac output, mixed venous oxygen saturation levels, and urinary output throughout the resuscitation period; however, there were no differences with regard to lactate, base excess, or oxygen consumption. Animals receiving HBOC-201 required significantly less fluid than any other group. Conclusion: In this model, hypotensive resuscitation with HBOC-201 restores tissue oxygenation and reverses anaerobic metabolism at significantly lower volumes when compared with HTS, HSD, pentastarch, or hetastarch solutions. These data suggest that HBOC-201 would be an effective primary resuscitation fluid for far-forward military or rural trauma settings where logistic constraints and prolonged transport times are common. However, when HBOC-201 is administered as a primary resuscitation fluid in hypotensive protocols, common clinical markers for determining adequacy of resuscitation may not be useful.

PURPOSE To assess endothelial function after arterial thrombosis creation and after administration of a novel thrombolytic regimen in a new porcine model. MATERIALS AND METHODS Untreated arteries that had undergone thrombosis for 90 minutes were compared to arteries treated with tissue plasminogen activator (tPA, 4 mg) and a combination of tPA and L-arginine (L-arg; 600 mmol/L). External iliac artery luminal diameter was measured with use of duplex ultrasonography. Endothelialdependent relaxation (EDR) and endothelial-independent relaxation (EIR) were measured with use of acetylcholine chloride (ACh) and sodium nitroprusside (NTP), respectively. Endothelial integrity was confirmed by scanning electron microscopy (SEM). Nitric oxide (NO) levels were determined with use of a chemiluminescent assay of its nitrite/nitrate metabolites (NO x ). RESULTS After thrombosis, EDR was decreased (69% ± 9.5; ACh=15 μg/min; n = 6). EDR remained unchanged after thrombolysis with tPA despite complete dissolution of thrombus (67% ± 5.7; ACh=15 μg/min; n = 5). Thrombolysis with use of tPA coupled with L-arg resulted in an increase in EDR (95% ± 4.9; ACh=15 μg/min; n = 5; P = .007). EIR was preserved in all groups, with uniform response to NTP. SEM analysis revealed intact endothelium in all groups. Local NO x levels were diminished after 90 minutes of thrombosis (49.3 μmol/L vs 40.8 μmol/L; P = .0002), but increased to 55.7 μmol/L after thrombolysis with tPA and L-arg ( P = NS). CONCLUSIONS Thrombus induces arterial dysfunction acutely without altering endothelial integrity. This dysfunction is ameliorated through regional administration of L-arg in combination with standard thrombolytic therapy, which increases local NO levels. This model allows the in-vivo study of thrombosis and alternative thrombolytic regimens. Regional enhancement of NO levels may prove to be an attractive adjunct in thrombolytic therapy.