Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia.

Nitric oxide (NO)-based therapies effectively inhibit neointimal hyperplasia in animal models of arterial injury and bypass grafting, but are not available clinically. We created a simple, effective, locally applied NO-eluting therapy to prevent restenosis after vascular procedures. We investigated the efficacy of perivascular delivery of two distinctly different diazeniumdiolate NO donors, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (short half-life) and diazeniumdiolated poly(acrylonitrile) (PAN/NO) (long half-life), in powder or gel form (30% poloxamer 407), at inhibiting neointimal hyperplasia using the rat carotid artery injury model. Two weeks postinjury, all of the NO-eluting therapies successfully reduced neointimal hyperplasia. However, most dramatically, PROLI/NO powder reduced intimal area by 91.2% (p<0.05) versus injury alone. PROLI/NO powder was noted to reduce the medial area (40.2% vs injury alone, p<0.05), whereas other groups showed no such effect. Three days postinjury, each NO treatment group significantly reduced cellular proliferation. However, inflammatory markers revealed a distinct pattern: PAN/NO groups displayed increased leukocyte infiltration (p<0.05), whereas PROLI/NO groups displayed less macrophage infiltration (p<0.05). In conclusion, perivascular delivery of diazeniumdiolate NO donors in powder or gel form effectively inhibits neointimal hyperplasia. Application of short-acting PROLI/NO powder most effectively inhibited neointimal hyperplasia and inflammation and may represent a simple, clinically applicable NO-eluting therapy to prevent neointimal hyperplasia and restenosis after open vascular interventions.

A reproducible porcine ePTFE arterial bypass model for neointimal hyperplasia.

BACKGROUND: Late failure of prosthetic vascular bypass grafting using expanded polytetrafluoroethylene (ePTFE) is secondary to the development of neointimal hyperplasia, most commonly at the distal anastomosis. To develop therapies that can improve upon current prosthetic vascular bypass grafting, a large animal model of prosthetic bypass grafting that results in reproducible neointimal hyperplasia is necessary. METHODS: We performed bilateral end-to-side carotid artery bypasses with 6 mm ePTFE in a porcine model (n = 11). We studied graft patency using magnetic resonance angiography (MRA, 3 wk), duplex ultrasonography (4 wk), and digital-subtraction contrast angiography (4 wk). Animals were sacrificed at 4 wk and morphometric analysis was performed. RESULTS: Of the 11 animals that underwent surgery, one pig died from respiratory compromise; of the remaining 10, graft patency was 90% at 4 wk. Peak systolic and end diastolic velocities were established for this model using ultrasonography. MRA, ultrasonography, and angiography confirmed graft patency and were complimentary tools to evaluate the grafts. Development of neointimal hyperplasia was reproducible at 4 wk in both the proximal and distal anastomoses (2.5 to 3 mm(2)) of the ePTFE bypass grafts. CONCLUSION: We developed a reproducible porcine ePTFE carotid artery bypass model for studying neointimal hyperplasia. Not only does this model allow for the manipulation and evaluation of potential therapies, but patency and neointimal hyperplasia can be easily evaluated by traditional means, such as MRA, ultrasonography, and angiography. This preclinical model is ideal for evaluation of novel therapies in vivo designed to inhibit neointimal hyperplasia following arterial reconstruction with prosthetic bypass grafting.

Percutaneous endovascular repair of ruptured abdominal aortic aneurysms.

HYPOTHESIS: Percutaneous endovascular repair of ruptured abdominal aortic aneurysms (RAAAs) has better outcomes than traditional open surgical repair. DESIGN: Single-center retrospective review. SETTING: University hospital tertiary referral center. PATIENTS: Thirty-seven RAAAs treated using endovascular repair (n = 15) or open surgery (n = 22). INTERVENTIONS: From January 1, 2000, through December 31, 2005, 15 RAAAs were treated with endovascular stent graft exclusion using commercially available systems. Twenty-two other patients undergoing standard open surgical repair during the same interval comprised a control group for comparison. MAIN OUTCOME MEASURES: Early outcomes of percutaneous endovascular repair of RAAAs. RESULTS: Among the endovascular group, the mean +/- SD age was 73 +/- 9.8 years, 86.6% were men (n = 13), and 20.0% had a preoperative systolic blood pressure of 80 mm Hg or lower (n = 3). An entirely percutaneous procedure was performed in the final 11 patients using arterial closure systems. Technical success of attempted endovascular exclusion was 100.0%. The mean +/- SD procedure time (107 +/- 30 minutes), transfusion requirements (6.6 +/- 4.7 U), and length of stay (3.0 +/- 6.8 days) were statistically significantly reduced compared with open surgery. The 30-day mortality was 6.7% (1 of 15) compared with an open surgery 30-day mortality of 13.6% (3 of 22). No late complications (pseudoaneurysm, infection, lymphocele, or neuropathy) occurred after a completely percutaneous technique during a mean follow-up of 12 months. CONCLUSION: Percutaneous endovascular repair of RAAAs is a more expedient and less morbid alternative than open surgical repair.

Technical limitations of carotid filter embolic protection devices.

Improved carotid artery stenting (CAS) results are credited to the development of embolic protection devices (EPDs). Reported are outcomes and technical failures of two classes of EPDs: distal balloon occlusion and distal filtration. We present a retrospective review of 206 CAS procedures from April 2001-September 2005. Filters (AccuNet, Angioguard, Filterwire, or Emboshield) were used in 98 cases (48%), distal balloon occlusion (PercuSurge) in 94 (46%), and no protection in 14. Data include demographics and procedural records. Mean age was 70 years (76% men, 24% women). At 30 days, there were no deaths, no myocardial infarctions, two major ipsilateral strokes (1%), two minor posterior strokes (1%), four transient ischemic attacks (2%), and one major access site complication (0.5%). Major neurologic events were equally divided between balloon occlusion and filters. Mean balloon occlusion time was 12 min, with only two patients (2%) manifesting reversible neurologic intolerance during flow arrest. In the last 100 cases, filter devices were preferentially used due to preserved antegrade flow. However, 11 cases (11%) necessitated intraoperative switching to balloon occlusion because of either extreme tortuosity or severe stenosis of the target lesion precluding passage of the filter element. CAS-specific equipment has improved procedural results. Despite theoretic advantages of filter EPDs, up to 10% of lesions are either too narrow or tortuous to allow safe passage of the filter element. Switching to a distal balloon occlusion system, which is well tolerated, may be preferred to unprotected predilation. Practitioners of CAS should be versed in both.

Sac behavior after aneurysm treatment with the Gore Excluder low-permeability aortic endoprosthesis: 12-month comparison to the original Excluder device.

BACKGROUND: The original Gore Excluder endoprosthesis (OGE) used both during and briefly after clinical trials was associated with less sac regression and more sac growth than some other devices, even without apparent endoleaks, presumably because of transmural movement of serous fluid across the expanded polytetrafluoroethylene material. In July 2004, the device was modified to decrease graft permeability. This study evaluated the efficacy of the new Excluder Low-Permeability Device (ELPD) at 1 year and compared it with the OGE and the Cook Zenith device (ZEN). METHODS: From Food and Drug Administration approval of the Excluder in November 2002 until June 2005, 283 patients underwent endovascular repair of abdominal aortic aneurysms with the Gore Excluder or the ZEN. Postoperative surveillance included computed tomographic scans at 1 and 12 months; 181 (64%) patients completed both scans. The 1-month computed tomographic scan served as a baseline, and the minor axis diameter, measured at the largest axial cut of the abdominal aortic aneurysm, was compared with the same measurement at 1 year. A sac size change of 5 mm or more was considered significant. Sixty patients treated with the OGE were compared with 72 patients treated with the ELPD. Forty-nine patients treated during the same time period with the ZEN, known for early sac shrinkage, were used as a reference. All measurements were performed by one observer from a digital workstation. Wilcoxon signed rank tests (pairwise) or Kruskal-Wallis tests (three groups) were used for intergroup comparison of continuous variables, whereas chi2 statistics or Fisher exact tests were used to compare categorical variables. RESULTS: Patient age and sex and mean maximum aneurysm diameter at baseline were similar among groups (P = .59, .27, and .46, respectively). Graft migration, stent fractures, acute surgical conversion, late abdominal aortic aneurysm rupture, or aneurysm-related deaths were not observed. Type II endoleak rates were similar between ELPD and ZEN (23.6% and 20.4%; P = .68). Although a higher rate of endoleaks was seen with OGE (36.7%), this was not significant when compared with the other two devices (P = .11). At 1 year, patients treated with ELPD had a sac regression rate that was significantly higher than that for patients treated with OGE (63.9% vs 25%; P < 0.001) and was similar to that for patients treated with ZEN (65.3%). Significant sac expansion was not observed with ELPD. CONCLUSIONS: At 1 year, similar to ZEN, significant aneurysm sac regression and minimal sac expansion were noted after endovascular repair of abdominal aortic aneurysms with ELPD. Low-porosity fabric used in the construction of endoprostheses seems to be an important factor in early aneurysm sac shrinkage. Long-term efficacy regarding the prevention of sac enlargement remains unclear, and further follow-up is suggested.

Intracoronary shunt-induced endothelial cell damage in porcine heart.

BACKGROUND: Injury to and dysfunction of the endothelium can compromise the patency of coronary arteries and lead to impaired perfusion of the heart. Such injury can occur after the application of an intravascular shunt and/or a snare to a coronary artery during bypass surgery. In this study, multiphoton microscopy was used to assess the integrity of endothelium in porcine coronary arteries subjected to shunting and snaring during off-pump coronary artery bypass grafting (OPCAB). MATERIALS AND METHODS: In open chest porcine, the left anterior descending artery was manipulated in different regions using snare and shunt to simulate OPCAB. Sections of left anterior descending artery were labeled with fluorescent dyes to evaluate the viability of the endothelium. The structural integrity of the endothelium was evaluated by calcein- and ethidium homodimer-mediated fluorescence. Endothelial functional viability was assessed by measuring cellular esterase activity, calcium mobilization, and endothelial nitric oxide synthase-mediated generation of nitric oxide using fluorescence dyes and multiphoton microscopy. RESULTS: Substantial endothelial damage was observed in shunted region of the coronary arteries. In contrast, endothelium remained structurally viable in regions that were snared, similar to control regions of the coronary arteries that were not manipulated. Esterase activity, calcium mobilization, and nitric oxide generation was greater in the control and snared regions of the coronary arteries in comparison to the shunted region. CONCLUSIONS: The use of intracoronary shunts led to structural damage and attenuation of endothelial function in porcine coronary arteries, whereas snared vessels maintained their viability and integrity, similar to the control sections. The routine use of shunts in OPCABG may lead to endothelial damage and possibly to long-term graft failure.

Intraoperative regional myocardial acidosis and reduction in long-term survival after cardiac surgery.

BACKGROUND: Regional myocardial acidosis, as measured with tissue pH electrodes during cardiac surgery, has been shown to be reflective of regional myocardial ischemia. This study examined the relationship between intraoperative regional myocardial acidosis and long-term survival of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: A total of 496 adult patients who underwent valve replacement, coronary artery revascularization, or both with intraoperative myocardial pH monitoring in the anterior and posterior left ventricular walls were followed up for 3 to 17 years (average 10.2 +/- 4.9 years) for all cause mortality. Regional myocardial acidosis in each patient was defined by the lower of the anterior and posterior wall pH values. RESULTS: A bivariate automatic interaction detection analysis identified three significant regional myocardial acidosis thresholds that affected long-term mortality: pH 37C less than 6.63 before aortic crossclamping, integrated mean pH 37C less than 6.34 during the period of aortic crossclamping, and pH 37C less than 6.73 at discontinuation of cardiopulmonary bypass. Cox proportional hazard regression analysis identified each of these thresholds to be independently determinant of survival, with pH 37C during aortic crossclamping having the highest risk ratio (risk ratio 2.15, 95% confidence interval 1.37-3.37). Raising pH 37C from lower than threshold before aortic crossclamping to higher than threshold during clamping increased the median survival by 40.2%. CONCLUSION: In adult patients undergoing cardiac surgery with cardiopulmonary bypass, regional myocardial ischemic acidosis before aortic crossclamping, during aortic crossclamping, and at discontinuation of cardiopulmonary bypass are independently associated with reduced long-term postoperative survival. Reversing or avoiding myocardial acidosis during cardiac surgery improves long-term patient survival.

The spectrum of colovesical fistula and diagnostic paradigm.

BACKGROUND: Our experience with colovesical fistula (CVF) over a 12-year period was reviewed to clarify its clinical presentation and diagnostic confirmation. METHODS: Twelve patients with CVF were identified. Presenting symptoms, etiologic factors, diagnostic investigations, and subsequent treatment were reviewed. RESULTS: Underlying etiologies were diverticular disease (75%), colon cancer (16%), and bladder cancer (8%). Pneumaturia (77%) was the most common presentation, followed by urinary tract infections, dysuria and frequency (45%), fecaluria (36%), hematuria (22%), and orchitis (10%). The ability of various preoperative investigations to identify a CVF were: computed tomography (CT) (90%), barium enema (BE) (20%), and cystography (11%), whereas cystoscopy, intravenous pyelogram (IVP), and colonoscopy were nondiagnostic. All patients underwent single- or multiple-staged repair of the fistula. CONCLUSIONS: In patients with a suspected CVF, we recommend CT followed by a colonoscopy as a first-line investigation to rule out malignancy as a cause of CVF. Other modalities should only be used if the diagnosis is in doubt or additional information is needed to plan operative management.

Evaluation of poly-N-acetyl glucosamine as a hemostatic agent in patients undergoing cardiac catheterization: a double-blind, randomized study.

BACKGROUND: This is the first blinded, randomized, placebo-controlled clinical trial to evaluate the efficacy of poly-N-acetyl glucosamine (p-GLcNAc) in improving hemostasis in patients undergoing cardiac catheterization. METHODS: Patients were randomly assigned to have either a placebo-treated (n = 17) or a p-GlcNAc-treated (n = 16) 3 x 3-cm patch topically placed at the femoral insertion site at the completion of their catheterization procedure with a mechanical pressure clamp applied over it. The amount of pressure was measured. RESULTS: Although the placebo group had slightly higher clamp pressure applied to the femoral arterial puncture site at the end of the catheterization procedure (189 +/- 47 vs. 149 +/- 49 mm Hg, p = 0.042), the time to effective hemostasis (16 +/- 7 vs. 10 +/- 3 minutes, p = 0.01) was decreased in the p-GlcNAc group by 37%. CONCLUSION: The application of p-GlcNAc patches improved hemostasis at the arterial puncture site in patients undergoing cardiac catheterization.

Multi-photon microscopic evaluation of saphenous vein endothelium and its preservation with a new solution, GALA.

BACKGROUND: Injury to endothelium can compromise the patency of bypass grafts harvested during coronary artery bypass graft (CABG) surgery. Maintaining structural and functional viability of endothelium in grafts may lead to improved long-term patency. The information gained from the application of multi-photon microscopy in transmission and epifluorescence mode was used to assess the structural and functional integrity of human saphenous vein segments stored in multiple preservation solutions, and to design a superior storage solution. METHODS: Multi-photon microscopy was used to image deep within saphenous vein tissue harvested from patients undergoing CABG for analysis of endothelial structure and function. Endothelial cell structural viability, calcium mobilization, and nitric oxide generation were determined using specific fluorescence markers. RESULTS: Within 60 minutes of harvest and storage in standard preservation solutions, calcium mobilization and nitric oxide generation were markedly diminished with more than 90% of endothelial cells no longer viable in the vein. In contrast, veins could be stored for 24 hours without substantial loss in cell viability in a newly formulated heparinized physiologic buffered salt solution containing glutathione, ascorbic acid, and L-arginine (GALA). CONCLUSIONS: Standard solutions in clinical use today led to a profound decline in saphenous vein endothelial cell viability, whereas the newly designed physiologic salt solution (GALA) maintained endothelial function and structural viability for up to 24 hours. The improvements seen from using GALA as a vessel storage medium may lead to greater long-term vein graft patency following CABG surgery.