Biomedical subjects

Peter L Faries

Publications and source records attributed to Peter L Faries.

At least 19 recordsLinked to original sources

PubMed2007

Protein kinase C-delta regulates migration and proliferation of vascular smooth muscle cells through the extracellular signal-regulated kinase 1/2.

BACKGROUND: Smooth muscle cell (SMC) migration and proliferation are early and crucial events in the pathogenesis of intimal hyperplasia, the primary cause of restenosis after vascular intervention. We tested the hypothesis that protein kinase C-delta (PKCdelta), a ubiquitously expressed intracellular protein kinase, regulates vascular SMC proliferation and migration. METHODS: Exogenous PKCdelta was expressed in cultured SMCs via stable transfection or adenovirus-mediated gene transfer. Conversely, endogenous PKCdelta was inhibited by means of targeted gene deletion (gene knock-out). Cell proliferation and migration were determined by (3)H-thymidine incorporation and 24-well transwell assay, respectively. RESULTS: We isolated and examined three A10 SMC lines in which PKCdelta was stably transfected. Compared with cells that were transfected with an empty vector, cells transfected with PKCdelta exhibited reduced ability to proliferate. Moreover, PKCdelta transfection inhibited SMC migration toward platelet-derived growth factor-BB. Similar inhibitory effects on proliferation and migration were also observed when PKCdelta was introduced into primary aortic SMCs via an adenoviral vector. Interestingly, SMCs isolated from PKCdelta knockout mice also displayed decreased chemotaxis and proliferation compared with PKCdelta(+/+) littermates, suggesting a complex yet critical role for PKCdelta. We studied the mitogen-activated protein kinase extracellular signal-regulated kinases (ERK) 1/2 as a possible signaling pathway for PKCdelta's inhibitory effect. PKCdelta overexpression diminished ERK1/2 activity. Molecular restoration of ERK activation reversed the inhibitory effect of PKCdelta on SMC proliferation and migration. CONCLUSIONS: We demonstrate that although normal migration and proliferation is lessened in SMCs deficient in PKCdelta, its prolonged activation also diminishes those behaviors. This suggests a dual, critical role for PKCdelta in SMC proliferation and migration, and thus intimal hyperplasia and restenosis.

Animals↗

PubMed2006

Analysis of outcomes following failed endovascular treatment of chronic limb ischemia.

Despite recent studies highlighting the advantages of endoluminal intervention in the management of chronic limb ischemia (CLI), outcomes following failed peripheral angioplasty remain less well described. We present a retrospective analysis of failed transluminal infrainguinal percutaneous arterial angioplasty with or without stenting (PTA/S) in patients with CLI. A database of patients undergoing infrainguinal PTA/S between 2002 and 2005 was maintained. Patients underwent duplex scanning follow-up at 2 weeks, 3 months, and every 6 months after the intervention. Angiograms were reviewed in all cases to assess lesion characteristics. Results were standardized to current Transatlantic Inter-Society Consensus (TASC) criteria. Kaplan-Meier survival analyses were performed to assess time-dependent outcomes. In total, our analysis involved 246 patients who underwent treatment for CLI using PTA/S. Eighteen percent of procedures (n = 46) were considered an intervention failure secondary to restenosis by duplex ultrasound, returning clinical symptoms, a nonhealing foot lesion, or the absence of a prior palpable pulse. Indications for the original procedure in patients whose PTA/S failed were tissue loss in 44%, claudication in 44%, and rest pain in 12%, while TASC lesion grades were A (0%), B (18%), C (18%), and D (64%). Of patients failing PTA/S, 4% failed in the first 30 days, 78% failed between 1 and 18 months, while 18% failed following 18 months, with a mean time to failure of 8.7 months. Also, 82% of PTA/S failures were candidates for a second endovascular procedure, 11% were suitable for only traditional open bypass, and 4% demonstrated progression of disease necessitating amputation. Of patients undergoing a second endovascular procedure, limb salvage rates were 86% at 12-month follow-up and there was a single periprocedural mortality and complication rate of 6.6%. Of patients requiring open surgical bypass after failed PTA/S, 20% (n = 1) required a major amputation and there were no mortalities. Failure of endoluminal therapy for treatment of lower extremity arterial occlusive disease is amenable to subsequent endovascular intervention for limb salvage with limited morbidity and mortality.

Adult↗

PubMed2006

Cerebral ischemia associated with PercuSurge balloon occlusion balloon during carotid stenting: Incidence and possible mechanisms.

BACKGROUND: Interruption of antegrade cerebral perfusion results in transient neurologic intolerance in some patients undergoing carotid angioplasty and stenting (CAS). This study sought to evaluate factors that contributed to the development of cerebral ischemia during PercuSurge balloon occlusion and techniques used to allow successful completion of the CAS procedure. METHODS: The PercuSurge occlusion balloon was used in 43 of 165 patients treated with CAS for high-grade stenosis (mean stenosis, 90%). All 43 patients were at increased risk for endarterectomy (7 restenosis, 3 irradiation, 3 contralateral occlusion, and 30 Goldman class II-III); 20% were symptomatic. Symptoms of cerebral hypoperfusion during temporary occlusion of the internal carotid artery occurred in 10 of 43 and included dysarthria (7/10), agitation (6/10), decreased level of consciousness (5/10), and focal hemispheric deficit (3/10). An incomplete circle of Willis or contralateral carotid artery occlusion, or both, was present in 8 of 10 patients. Symptoms resulting from PercuSurge balloon occlusion were managed by balloon deflation with or without evacuation of blood from the internal carotid artery using the Export catheter. All symptoms resolved completely without deficit after deflation of the occlusion balloon. RESULTS: The development of neurologic symptoms after initial PercuSurge balloon inflation and occluded internal carotid artery flow was associated with a decrease in the mean Glasgow Coma Scale (GCS) from 15 to 10 (range, 9 to 14); the GCS returned to normal after occlusion balloon deflation and remained normal during subsequent reinflation. The mean time to spontaneous recovery of full neurologic function was 8 minutes (range, 4 to 15 minutes). No thrombotic or embolic events were present on cerebral angiography or computed tomography scan. Balloon reinflation was performed after a mean reperfusion interval of 10 minutes after full neurologic recovery (range, 4 to 20 minutes). The mean subsequent procedure duration was 11.9 minutes (range, 6 to 21 minutes). No recurrence of neurologic symptoms occurred when the occlusion balloon was reinflated. All 10 patients underwent successful CAS without occlusion, dissection, cerebrovascular accident, or death. CONCLUSION: Several factors may contribute to the development of neurologic intolerance during CAS with balloon occlusion. Elucidation of the protective cellular mechanisms that invoke ischemic tolerance after the initial transient ischemic event may enable CAS with embolic protection in patients who cannot tolerate initial interruption of antegrade cerebral perfusion.

Aged↗

PubMed2006

PKCdelta is necessary for Smad3 expression and transforming growth factor beta-induced fibronectin synthesis in vascular smooth muscle cells.

OBJECTIVE: The purpose of these studies is to investigate the mechanism by which transforming growth factor (TGF)beta1 regulates the synthesis of the extracellular matrix protein fibronectin (FN). METHODS AND RESULTS: TGFbeta1 elicited a time-dependent induction of FN protein and mRNA in A10 rat aortic smooth muscle cells (SMCs). Ectopic expression of Smad3 in A10 cells stimulated both basal and TGFbeta1-induced FN expression, whereas expression of Smad7 eliminated the TGFbeta response. Because TGFbeta activated PKCdelta in SMCs, we tested the role of PKCdelta in regulation of FN expression. Inhibition of PKCdelta activity by rottlerin or dominant-negative adenovirus (AdPKCdelta DN) blocked TGFbeta1's induction of FN, whereas overexpression of PKCdelta enhanced TGFbeta's effect. Moreover, aortic SMCs isolated from PKCdelta(-/-) mice exhibited diminished FN induction in response to TGFbeta. Furthermore, we found that Smad3 protein and mRNA were markedly reduced in AdPKCdelta DN-treated A10 cells and in PKCdelta null cells. Finally, restoring Smad3 in rottlerin-treated A10 and PKCdelta null cells rescues the ability of TGFbeta to upregulate FN protein and mRNA expression. CONCLUSIONS: Our data suggest that TGFbeta-activated PKCdelta is critical to maintain normal expression of Smad3, which in turn is required for the induction of fibronectin. PKCdelta represents a promising target for treating the fibroproliferative response after arterial injury.

Adenoviridae↗

PubMed2006

The development of endotension is associated with increased transmission of pressure and serous components in porous expanded polytetrafluoroethylene stent-grafts: characterization using a canine model.

OBJECTIVE: This study used a canine model of abdominal aortic aneurysms (AAAs) to compare intra-aneurysmal pressure and thrombus formation after exclusion with Dacron and expanded polytetrafluoroethylene (ePTFE) stent-grafts. METHODS: Prosthetic AAAs with implanted strain-gauge pressure transducers were treated by stent-graft exclusion using Food and Drug Administration-approved devices in 10 mongrel dogs: five Dacron (AneuRx) and five ePTFE (original Excluder). Intra-aneurysmal pressure was measured over 4 weeks after AAA exclusion and indexed to the systemic pressure, represented as a percentage of a simultaneously obtained systemic pressure (value = 1.0). Magnetic resonance imaging (MRI) of the intra-aneurysmal thrombus was performed at 1, 2, and 4 weeks after exclusion and expressed as a signal-to-noise ratio (S:N) to control for background signal intensity. Comparisons of pressures and S:N between the two stent-grafts was analyzed with the Student's t test. Intra-aneurysmal thrombus was characterized histologically. RESULTS: In animals excluded with both Dacron and ePTFE stent-grafts, the intra-aneurysmal pressure was nonpulsatile and reduced to <30% of systemic pressure. Significantly greater pressure transmission was observed after AAA exclusion using ePTFE compared with Dacron stent grafts (systolic pressure: ePTFE, 0.28 +/- 0.12 vs Dacron, 0.11 +/- 0.02, P < .001; mean pressure: ePTFE, 0.16 +/- 0.08 vs Dacron, 0.06 +/- 0.02, P < .001). MRI confirmed the absence of perfusion in all aneurysms. The T1-weighted signal intensity remained persistently elevated (S:N at 1 week, 2.7 +/- 0.4 vs 2 weeks, 4.0 +/- 0.2 vs 4 weeks, 5.4 +/- 1.3) in ePTFE-treated intra-aneurysmal thrombus, suggesting an absence of thrombus organization. In contrast, progressive evolution of T1 signal intensity in aneurysms excluded by Dacron stent-grafts was consistent with maturation from intact red blood cells (S:N at 1 week, 3.3 +/- 0.4) to methemoglobin (S:N at 2 weeks, 6.1 +/- 0.8), and then hemosiderin and ferritin (S:N at 4 weeks, 2.4 +/- 0.5). Histologically, ePTFE-excluded aneurysms contained poorly organized thrombus with red blood cell fragments and haphazardly arranged fibrin deposition indicative of active remodeling and continued influx of transudated serum. In aneurysms excluded by Dacron stent-grafts, dense, mature collagenous connective tissue and organized fibrin were present, indicative of greater thrombus organization. CONCLUSIONS: Stent-graft treatment reduces intra-aneurysmal pressure to <30% of systemic pressure when no endoleak is present; however, significantly greater pressure is present in aneurysms treated with porous ePTFE stent-grafts than Dacron grafts. Histologic and MRI imaging analysis suggest that active transudation of serous blood components may be contributing to this increased intra-aneurysmal pressure.

Animals↗

PubMed2006

Successful percutaneous treatment of gluteal claudication secondary to isolated bilateral hypogastric stenoses.

We report an unusual case of bilateral buttock claudication at ambulation of less than two blocks in a 57-year-old man with normal lower-extremity segmental pressure on noninvasive exercise testing. He was found to have bilateral high-grade internal iliac artery stenoses on arteriography. Both sides were successfully treated in a staged fashion via a contralateral approach with percutaneous transluminal angioplasty and a balloon-expandable stent, with complete symptom resolution. A clinical vascular examination with normal findings of the common iliac, external iliac, and common and superficial femoral arteries eliminates significant vascular obstruction as a cause of claudication. However, internal iliac occlusive disease may be suspected when symptoms are limited to the gluteal musculature and other causes are eliminated. Percutaneous interventions can be of diagnostic and therapeutic value.

Angioplasty, Balloon↗

PubMed2006

Analysis of parameters associated with hypotension requiring vasopressor support after carotid angioplasty and stenting.

INTRODUCTION: Systemic hypotension has been observed for up to 36 hours in response to stimulation of the carotid baroreceptor by carotid angioplasty and stenting (CAS). The aim of this study was to identify risk factors and cardiac outcomes for postprocedural hypotension requiring vasopressor support after CAS. METHODS: Between 2003 and 2005, 143 patients (87 men; mean age, 75 years) with high-grade carotid artery stenosis (mean, 87.3%) were treated with CAS and prospectively entered into a vascular registry. Data were retrospectively analyzed to determine factors predictive of hypotension requiring vasopressor support after CAS. Atropine and appropriate intravenous crystalloid solution were administered during CAS. For the first 30 patients, atropine was only used for symptomatic patients but then became routine and was used for all patients with primary carotid stenosis. Hypotension (systolic blood pressure <90 mm Hg or a mean arterial blood pressure <50 mm Hg) unresponsive to conservative measures was treated with vasopressors (phenylephrine or norepinephrine). Patients were stratified into three groups based on hypotension requiring vasopressors: (1) no vasopressors, (2) vasopressors for < or = 24 hours (short duration), and (3) vasopressors for >24 hours (prolonged duration). Risk factors for hypotension requiring vasopressors were analyzed by univariate and multivariate logistic regression analysis. RESULTS: Postprocedural hypotension requiring vasopressor treatment was seen in 16 (11%) of 143 of patients, with 6 (4%) requiring vasopressor support for >24 hours. Mean duration of vasopressor administration for all patients was 17 +/- 10 hours (range, 6 to 36 hours). By univariate analysis, a history of a previous myocardial infarction (P = .02) or use of the PercuSurge occlusion balloon (P = .05) were both associated with increased incidence of short duration (</=24 hours) use of vasopressors, and female sex (P = .03) and age >80 years old (P = .02) were associated with prolonged (>24 hours) vasopressor requirement. On multivariate analysis adjusted for age and sex, a history of myocardial infarction (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.0 to 16.4; P = .05) remained an independent predictor of short-duration vasopressors. On multivariate analysis, female sex (OR, 10.9; 95% CI, 1.2 to 100.4; P = .04) and age >80 years old (OR, 13.8, 95% CI, 1.5 to 127.2; P = .02) remained independent predictors of prolonged vasopressor use. The incidence of periprocedural myocardial infarctions, arrhythmias, or congestive heart failure did not differ between those patients who did not receive vasopressors (5/127) and those who received vasopressors for a short (< or = 24 hours) duration (1/10, P = NS) or prolonged (>24 hours) duration (0/6, P = NS). CONCLUSION: Prolonged hypotension requiring vasopressor support occurs in a minority of patients after CAS, with higher incidences in older women. In contrast, hypotension requiring a more limited duration of vasopressor use occurs more commonly in patients who had a prior myocardial infarction, independent of age or sex. In this cohort of patients, vasopressors required for hypotension were not associated with an increased incidence of periprocedural cardiac complications. Despite the increased incidence of prolonged hypotension in older women, this study demonstrates that CAS can be performed without an increase in cardiac morbidity in older women.

Aged↗

PubMed2006

Evaluation of the accuracy of a wireless pressure sensor in a canine model of retrograde-collateral (type II) endoleak and correlation with histologic analysis.

BACKGROUND: The utility of intra-aneurysmal pressure determination is dependent on the ability to measure pressure in the presence of endoleak and thrombosis. In this study, the accuracy of a CardioMEMS wireless pressure sensor (CardioMEMS, Atlanta, Ga) transducer in the presence of thrombus associated with type II endoleak was measured. METHODS: Type II endoleaks were created in four mongrel dogs by implanting four collateral arterial side branches (lumbar and caudal mesenteric arteries) as a Carrel patch onto a 3-cm prosthetic polytetrafluoroethylene abdominal aortic aneurysm (AAA). The aneurysm was excluded 2 weeks later from antegrade perfusion by a stent graft. The wireless pressure sensor was positioned in the AAA external to the stent graft. A Konigsberg intraluminal solid-state strain-gauge pressure transducer (Konigsberg Instruments, Pasadena, Calif) that is accurate in the presence of thrombus served as the control to determine AAA pressure. Both of the transducers were implanted on the luminal surface of the aneurysm, 180 degrees opposite from the Carrel patch and endoleak channel. Intra-aneurysmal pressure resulting from the type II endoleak was measured twice daily for 4 weeks using both transducers. A total of 56 pre-exclusion and 224 post-exclusion distinct pressure determinations were made. Intra-aneurysmal pressure was indexed to the systemic pressure that was simultaneously measured by a strain-gauge pressure transducer implanted in the native aorta. Histologic analysis of the aneurysm contents was performed with hematoxylin and eosin. RESULTS: The intra-aneurysmal systolic, mean, and pulse pressures produced by the type II endoleak were significantly lower than systemic pressure in all animals and were < 60% of systemic pressure (P < .001). Close correlation between the wireless transducer and the control strain-gauge transducer was observed (R = 0.83, P < .001). Arteriography and Doppler ultrasound documented retrograde flow through the aneurysm side branches and persistent endoleak patency up to the time of euthanasia. Pathologic analysis demonstrated the endoleak channel to be patent and separated from the transducers by thrombus, which surrounded both transducers. CONCLUSIONS: Intra-aneurysmal pressure generated by type II endoleaks may be accurately measured through thrombus using a wireless pressure sensor in the canine model. The wireless sensor has the potential for clinical applicability in diagnosing and characterizing type II endoleaks.

Angioplasty↗

PubMed2006

Simulation improves resident performance in catheter-based intervention: results of a randomized, controlled study.

OBJECTIVES: Surgical simulation has been shown to enhance the training of general surgery residents. Since catheter-based techniques have become an important part of the vascular surgeon's armamentarium, we explored whether simulation might impact the acquisition of catheter skills by surgical residents. METHODS: Twenty general surgery residents received didactic training in the techniques of catheter intervention. Residents were then randomized with 10 receiving additional training with the Procedicus, computer-based, haptic simulator. All 20 residents then participated in 2 consecutive mentored catheter-based interventions for lower extremity occlusive disease in an OR/angiography suite. Resident performance was graded by attending surgeons blinded to the resident's training status, using 18 procedural steps as well as a global rating scale. RESULTS: There were no differences between the 2 resident groups with regard to demographics or scores on a visuospatial test administered at study outset. Overall, residents exposed to simulation scored higher than controls during the first angio/OR intervention: procedural steps (simulation/control) (50 +/- 6 vs. 33 +/- 9, P = 0.0015); global rating scale (30 +/- 7 vs. 19 +/- 5, P = 0.0052). The advantage provided by simulator training persisted with the second intervention (53 +/- 6 vs. 36 +/- 7, P = 0.0006); global rating scale (33 +/- 6 vs. 21 +/- 6, P = 0.0015). Moreover, simulation training, particularly for the second intervention, led to enhancement in almost all of the individual measures of performance. CONCLUSION: Simulation is a valid tool for instructing surgical residents and fellows in basic endovascular techniques and should be incorporated into surgical training programs. Moreover, simulators may also benefit the large number of vascular surgeons who seek retraining in catheter-based intervention.

Angiography↗

PubMed2006

Safety and efficacy of carotid angioplasty and stenting in high-risk patients.

Performance of carotid endarterectomy (CEA) may be associated with an increased risk in patients with significant comorbid medical conditions, neck irradiation, or previous CEA. This study compared the results of CEA with carotid angioplasty and stenting (CAS) in high-risk patients treated for carotid stenosis. Five hundred forty-five patients who underwent CEA and 148 patients who underwent CAS were evaluated. For patients undergoing CEA, general anesthesia was used in 91 per cent, electroencephalographic monitoring was used in 63 per cent, and shunting was performed in 19.8 per cent. Cerebral protection devices were used in 145/148 of CAS cases, and self-expanding stents were used in all cases. Evaluated end points included major cardiovascular events, and a composite of death, stroke, or myocardial infarction for the duration of the follow-up. Mean follow-up was 18 months for CAS and 23 months for CEA. Significant differences were present in patient age (CAS, 75 +/- 11.0 years vs CEA, 71 +/- 9 years, P = 0.012), however, there were no significant differences (P = NS) in gender or smoking history. The mean modified Goldman Score was significantly higher for CAS (21.1 +/- 14.8 [95% confidence interval = 18, 24]) than for CEA (6.3 +/- 6.8 [95% confidence interval = 5.7, 6.9]; P = 0.0001) patients. The incidence of periprocedural complications did not vary significantly between patients treated with CAS (CVA, 1.4%; myocardial infarction [MI], 1.4%; death, 0.7%; CVA/MI/death, 3.4%) compared with CEA (CVA, 1.8%; MI, 1.1%; death, 0.4%; CVA/MI/death, 4.0%). CAS is equivalent to CEA in safety and efficacy, even when performed in patients who may be at increased surgical risk.

Age Factors↗

PubMed2005

Protein kinase C delta induces apoptosis of vascular smooth muscle cells through induction of the tumor suppressor p53 by both p38-dependent and p38-independent mechanisms.

Apoptotic death of vascular smooth muscle cells (SMCs) is a prominent feature of blood vessel remodeling. In the present study, we examined the novel PKC isoform protein kinase C delta (PKCdelta) and its role in vascular SMC apoptosis. In A10 SMCs, overexpression of PKCdelta was sufficient to induce apoptosis, whereas inhibition of PKCdelta diminished H2O2-induced apoptosis. Moreover, evidence is provided that the tumor suppressor p53 is an essential mediator of PKCdelta-induced apoptosis in SMCs. Activation of PKCdelta led to accumulation as well as phosphorylation of p53 in SMCs; this induction correlated with apoptosis. Furthermore, blocking p53 induction with small interference RNA or targeted gene deletion prevented PKCdelta-induced apoptosis, whereas restoring p53 expression rescued the ability of PKCdelta to induce apoptosis in p53 null SMCs. We also establish that PKCdelta regulates p53 at both transcriptional and post-translational levels. Specifically, the transcriptional regulation required p38 MAPK, whereas the post-translational modification, at least for serine 46, did not involve MAPK. Additionally, PKCdelta, p38 MAPK, and p53 co-associate in cells under conditions favoring apoptosis. Together, our data suggest that SMC apoptosis proceeds through a pathway that involves PKCdelta, the intermediary p38 MAPK, and the downstream target tumor suppressor p53.

Adenoviridae↗

PubMed2005

Tibial angioplasty as an alternative strategy in patients with limb-threatening ischemia.

The purpose of this study was to assess the technical feasibility and early outcome of tibial angioplasty for a subset of patients with limb-threatening ischemia who were not candidates for bypass grafting. A retrospective analysis was conducted of 19 patients (7 male, 12 female) who underwent crural angioplasty for limb-threatening ischemia using 0.018- or 0.014 inch-based systems. Contraindications to bypass were insufficient conduit in 7 patients and severe comorbid illness in 12. Concurrent treatment of inflow lesions was performed in 12 of 20 limbs via either angioplasty alone (5) or combined with stenting (12). Outcome measures were ankle-brachial indices (ABI), relief of rest pain, and healing or healed wounds. Twenty-three vessels were treated, including 14 tibial occlusions and 9 stenoses. The average length of diseased segment was 11 cm (range, 3-25 cm). Thirteen of 14 occlusions were treated with subintimal recanalization, the remainder with laser recanalization. Technical success was achieved in 22 of 23 treated vessels. Mean preoperative ABI was 0.53 and mean postoperative ABI was 0.85. Palpable pulses were present in 11 of 20 limbs (55%). There was one perioperative mortality (5.2%). Mean follow-up was 3 months. Three failures occurred requiring amputation (15.8%). The remaining 16 patients were improved with healing (8) or healed (4) wounds and relief of rest pain (4). These results indicate that technical success may be achieved with outflow lesion angioplasty in the majority of patients encountered. The durability of this method of therapy is unknown, and our length of follow-up is not sufficient to answer this question. However, an attempt at angioplasty appears justified before primary amputation and before surgical bypass in those patients at high risk for intervention.

Aged↗

PubMed2005

Percutaneous endovascular treatment for chronic limb ischemia.

Percutaneous transluminal methods of revascularization for chronic limb ischemia have traditionally been used as an adjunctive or secondary mode of treatment. This study examines the outcomes of patients treated via endovascular methods as the primary form of treatment. The records of 66 patients (average age, 71.3 years; range, 53 to 92) with chronic limb ischemia treated from November 2000 to January 2002 at a single institution with endovascular methods were retrospectively reviewed. Thirty-one patients had disabling claudication, 15 had rest pain, 17 had minor tissue loss, and 3 had major tissue loss. There were 94 lesions in the 66 limbs: 45 lesions in the superficial femoral artery, 28 lesions in the popliteal artery, and 21 lesions in tibial arteries. Occlusive lesions were treated by subintimal angioplasty. Stenoses were treated by percutaneous transluminal angioplasty (PTA). The median length of the lesions was 12 cm. Forty-six stents were placed in 32 patients; 34 patients did not receive stents. The approach was contralateral in 71% (47/66) and ipsilateral in 29% (19/66) of cases. Patients were followed up with physical exam, anklebrachial index (ABI), and duplex ultrasonography. Post-intervention medical treatment included aspirin and clopidogrel. Long-term patency was correlated with age, comorbidities, risk factors, and the use of stents in addition to angioplasty. Endovascular treatment was technically successful in 65 of 66 patients (98%). Residual stenosis (<30%) was found in three cases, two in patients with PTA alone and one patient with PTA and a stent. Mean length of follow-up was 6.3 months (range, 6 weeks to 15 months). Post-intervention ABI improved from a mean of 0.65 to a mean of 1.01 (p < 30.05). The perioperative complication rate was 9% and included three cases of hematoma and one case each of thrombosis, lymphocele, and rash reaction to medications. Outcome measures included primary patency (89%), assisted primary patency (96%), and limb salvage (97%) at 6 months. Restenosis of >50% occurred in four patients and occlusion occurred in two. At 6 months, patients with one or more stents had a patency rate of 84% (27/32), whereas those without a stent had a patency rate of 94% (32/34) (p = NS). Endovascular treatment is a safe, feasible, and effective method with a high short-term patency rate and may be used as an alternative to bypass for chronic limb ischemia.

Aged↗

PubMed2005

Multimodal percutaneous intervention for critical venous occlusive disease.

Critical deep venous thrombosis and occlusion constitutes a small percentage of patients with venous disease, who exhibit severe symptomatology. This study examined the results of multimodal percutaneous therapy for the treatment of complex critical venous thrombotic and occlusive disease. Twenty-five patients presented with critical venous thromboses or occlusions (11 with debilitating unilateral lower extremity edema causing ambulatory impairment, 2 with debilitating bilateral lower extremity edema, 3 with phlegmasia cerulea dolens, 2 with venous claudication, 2 with superior vena cava (SVS) syndrome with respiratory compromise, 4 with debilitating upper extremity edema, and 1 with renal insufficiency). Therapeutic modalities including thrombolysis, mechanical thrombectomy, percutaneous venoplasty and stent placement, temporary inferior vena cava filtration, and ultrasound guidance were used in all cases in conjunction with long-term systemic anticoagulation. The venous access site was determined by the anatomic location of the lesion and included popliteal, femoral, brachial, and lesser saphenous. Patients were followed with clinical exam and duplex surveillance. Resolution of symptoms was achieved in 18 of 25 patients (72%) and partial resolution occurred in 4 of 25 (16%). Failure of treatment identified as both lack of clinical response and evidence of continued venous thrombosis occurred 3 of 25 patients (12%). Restoration of arterial pulses and limb salvage was achieved in the three patients with phlegmasia cerulea dolens and acute limb-threatening ischemia. Both patients with SVC syndrome experienced resolution of respiratory compromise and facial edema. The mean length of follow-up was 11 +/- 2.7 months. Complications included transfusion requirement (2), hematuria (2), retroperitoneal hematoma (1), and cellulitis (1). Acute critical venous thrombotic and occlusive disease is responsive to multimodal percutaneous treatment. The relief of pain and resolution of acutely life and limb-threatening conditions in this most severely symptomatic subset of patients represents the immediate goal of treatment.

Algorithms↗

PubMed2005

Analysis of anatomic factors and age in patients undergoing carotid angioplasty and stenting.

Recent data suggest that patient age >80 years may be associated with increased risk of periprocedural complications from carotid angioplasty and stenting (CAS). In this study, we analyzed anatomic risk factors in patients undergoing CAS based on age >80 or <80 years. Our hypothesis was that patients >80 would have more challenging anatomy. Between February 2003 and August 2004, 82 patients underwent CAS. Images for 57 lesions were available for review. Eighteen patients were > or =80 years old and 39 were <80. Cerebral protection devices, including EPI Filterwire, Percusurge, Accunet, and Angioguard, were used in all but two cases; and self-expanding stents (Wallstent, NexStent, Acculink, Precise) were placed in all. Arterial anatomic characteristics were assigned a score based on complexity and associated procedural risk. Characteristics evaluated using angiographic images were aortic arch elongation classification, arch calcification, common carotid/innominate stenosis, common carotid tortuosity, internal carotid tortuosity, index lesion length, index lesion calcification, and index lesion stenosis. Statistical analysis was performed using Fisher's exact test. CAS was successfully completed in 98% of cases. The two patients in whom we could not perform CAS were 79 and 83 years old. The anatomic characteristics that were statistically significantly more complex/severe in patients > or =80 were arch calcification (p = 0.045), common carotid/innominate stenosis (p = 0.023), common carotid tortuosity (p = 0.049), and internal carotid tortuosity (p = 0.032). There was no statistically significant difference in arch elongation classification, lesion length, lesion calcification, or stenosis severity (p = nonsignificant). Overall, patients > or =80 years had an increased incidence of complex anatomic risk factors compared to younger patients (p < 0.001). Cerebrovascular accident without residual deficits occurred in two patients; both were >80 years old. Complex arterial anatomy is more often present in patients >80 years and may explain the increased complication rates associated with CAS. Pre- or intraoperative consideration of these characteristics may help provide better risk assessment in candidates for CAS.

Age Factors↗

PubMed2005

A canine model to study the significance and hemodynamics of type II endoleaks.

OBJECTIVE: The clinical significance of Type 2 endoleak after endovascular repair of abdominal aortic aneurysms (AAA) remains incompletely delineated. This study describes the development of a novel canine model that allows for continuous monitoring of intraaneurysmal pressure in the setting of Type 2 endoleak. METHODS: Infrarenal AAA were created in 10 mongrel dogs by implanting a prosthetic aneurysm containing an intraluminal, solid-state, strain gauge pressure transducer which is able to measure pressures in both solid and liquid media. A segment of native aorta with two or more patent side branch vessels was reimplanted into the prosthetic aneurysm using a Carrel patch. Four animals had two lumbar vessels implanted; two had two lumbar vessels and the caudal mesenteric artery implanted, and four control animals had no vessels reimplanted. Retrograde flow in the aneurysmal side branches caused a Type 2 endoleak after the aneurysm was excluded from antegrade flow by deploying a stent graft. Both systemic and intra-sac pressures were measured daily for up to 90 days after endovascular exclusion and indexed to systemic pressure. Endoleak patency and flow were assessed with digital subtraction angiography, duplex ultrasound, and cine-magnetic resonance angiography (MRA). Histological characterization of the intraaneurysmal contents was performed. RESULTS: Before endovascular exclusion, the systolic, mean arterial, and pulse pressure within the aneurysmal sac closely matched that of the systemic circulation (systolic, 0.96 +/- 0.22; mean, 0.94 +/- 0.21; pulse pressure, 0.97 +/- 0.22) (R value, 0.97). Endovascular exclusion in animals with no collateral side branch vessels resulted in no endoleak and significantly reduced intraaneurysmal pressure when compared to systemic pressure, with systolic, mean arterial, and pulse pressure 0.172 +/- 0.05, 0.137 +/- 0.05, and 0.098 +/- 0.02, respectively (P < 0.001). In animals with Type 2 endoleaks, the pressures were lower than systemic pressure, but statistically significant in their difference from the control group. The systolic pressure of those with Type 2 endoleaks was 0.702 +/- 0.048; mean arterial pressure was 0.784 +/- 0.028, and pulse pressure was 0.406 +/- 0.031 when indexed to systemic pressure (P < 0.001). Cine-MRA and Duplex ultrasound documented persistent patency of the Type 2 endoleaks throughout the study period in animals with multiple side branches. CONCLUSION: Intraaneurysmal pressure in the setting of Type 2 endoleaks may be accurately determined using this canine model. Intraaneurysmal pressure is maintained at a significant level in the context of this retrograde collateral perfusion, suggesting that persistent Type 2 endoleaks are of clinical significance. This model may serve to allow further evaluation and characterization of Type 2 endoleaks.

Angiography, Digital Subtraction↗

PubMed2005

Carotid angioplasty and stent-induced bradycardia and hypotension: Impact of prophylactic atropine administration and prior carotid endarterectomy.

OBJECTIVE: We compared the physiologic effect of selective atropine administration for bradycardia with routine prophylactic administration, before balloon inflation, during carotid angioplasty and stenting (CAS). We also compared the incidence of procedural bradycardia and hypotension for CAS in patients with primary stenosis vs those with prior ipsilateral carotid endarterectomy (CEA). METHODS: A total of 86 patients were treated with CAS at 3 institutions. Complete periprocedural information was available for 75 of these patients. The median degree of stenosis was 90% (range, 60%-99%). Indications for CAS were severe comorbidities (n = 49), prior CEA (n = 21), and prior neck radiation (n = 5). Twenty patients with primary lesions were treated selectively with atropine only if symptomatic bradycardia occurred (nonprophylactic group). Thirty-four patients with primary lesions received routine prophylactic atropine administration before balloon inflation or stent deployment (prophylactic group). The 21 patients with prior CEA received selective atropine treatment only if symptomatic bradycardia occurred (prior CEA group) and were analyzed separately. Mean age and cardiac comorbidities did not vary significantly either between the prophylactic and nonprophylactic atropine groups or between the primary and prior CEA patient groups. Outcome measures included bradycardia (decrease in heart rate >50% or absolute heart rate <40 bpm), hypotension (systolic blood pressure <90 mm Hg or mean blood pressure <50 mm Hg), requirement for vasopressors, and cardiac morbidity (myocardial infarction or congestive heart failure). RESULTS: The overall incidence of hypotension and bradycardia in patients treated with CAS was 25 (33%) of 75. A decreased incidence of intraoperative bradycardia (9% vs 50%; P < .001) and perioperative cardiac morbidity (0% vs 15%; P < .05) was observed in patients with primary stenosis who received prophylactic atropine as compared with patients who did not receive prophylactic atropine. CAS after prior CEA was associated with a significantly lower incidence of perioperative bradycardia (10% vs 33%; P < .05), hypotension (5% vs 32%; P < .05), and vasopressor requirement (5% vs 30%; P < .05), with a trend toward a lower incidence of cardiac morbidity (0% vs 6%; not significant) as compared with patients treated with CAS for primary carotid lesions. There were no significant predictive demographic factors for bradycardia and hypotension after CAS. CONCLUSIONS: The administration of prophylactic atropine before balloon inflation during CAS decreases the incidence of intraoperative bradycardia and cardiac morbidity in primary CAS patients. Periprocedural bradycardia, hypotension, and the need for vasopressors occur more frequently with primary CAS than with redo CAS procedures. On the basis of our data, we recommend that prophylactic atropine administration be considered in patients with primary carotid lesions undergoing CAS.

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PubMed2005

Treatment of type II endoleaks with a novel polyurethane thrombogenic foam: induction of endoleak thrombosis and elimination of intra-aneurysmal pressure in the canine model.

OBJECTIVE: The clinical significance and treatment of retrograde collateral arterial perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) have not been completely characterized. A canine abdominal aortic aneurysm model of type II endoleak with an implanted pressure transducer was used to evaluate the use of polyurethane foam to induce thrombosis of type II endoleaks. The effect on endoleak patency, intra-aneurysmal pressure, and thrombus histology was studied. METHODS: Prosthetic aneurysms with an intraluminal, solid-state, strain-gauge pressure transducer were created in the infrarenal aorta of 14 mongrel dogs. Aneurysm side-branch vessels were reimplanted into the prosthetic aneurysm of 10 animals by using a Carrel patch. Type II (retrograde) endoleaks were created by excluding the aneurysm from antegrade perfusion with an impermeable stent graft. Thrombosis of the type II endoleak was induced by implantation of polyurethane foam into the prosthetic aneurysm sac of four animals. Six animals with type II endoleaks were not treated. In four control animals, no collateral side branches were reimplanted, and therefore no endoleak was created. Intra-aneurysmal and systemic pressures were measured daily for 60 to 90 days after the implantation of the stent graft. Endoleak patency and flow were assessed during surgery and at the time of death by using angiographic imaging and duplex ultrasonography. Histologic analysis of the intra-aneurysmal thrombus was also performed. RESULTS: Intra-aneurysmal pressure values are indexed to systemic pressure and are represented as a percentage of the simultaneously obtained systemic pressure, which has a value of 1.0. All six animals with untreated type II endoleaks maintained patency of the endoleak and side-branch arteries throughout the study period. Compared with control aneurysms that had no endoleak, animals with patent type II endoleaks exhibited significantly higher intra-aneurysmal pressurization (systolic pressure: patent type II endoleak, 0.702 +/- 0.283; control, 0.172 +/- 0.091; P < .001; mean pressure: endoleak, 0.784 +/- 0.229; control, 0.137 +/- 0.102; P < .001; pulse pressure: endoleak, 0.406 +/- 0.248; control, 0.098 +/- 0.077; P < .001; P < .001 for comparison for all groups by analysis of variance). Treatment of the type II endoleak with polyurethane foam induced thrombosis of the endoleak and feeding side-branch arteries in all four animals with type II endoleaks. This resulted in intra-aneurysmal pressures statistically indistinguishable from the controls (systolic pressure, 0.183 +/- 0.08; mean pressure, 0.142 +/- 0.09; pulse pressure, 0.054 +/- 0.04; not significant). Angiography and histology documented persistent patency up to the time of death (mean, 64 days) for untreated type II endoleaks and confirmed thrombosis of polyurethane foam-treated endoleaks in all cases. CONCLUSIONS: Untreated type II endoleaks were associated with intra-aneurysmal pressures that were 70% to 80% of systemic pressure. Treatment with polyurethane foam resulted in a reduction of intra-aneurysmal pressure to a level that was indistinguishable from control aneurysms that had no endoleak. CLINICAL RELEVANCE: Endovascular repair of abdominal aortic aneurysms is dependent on the successful exclusion of the aneurysm from arterial circulation. Type II endoleaks originate from retrograde flow into the aneurysm sac. This study demonstrates the use of polyurethane foam to induce thrombosis in a canine model of a type II endoleak, thereby reducing intra-aneurysmal pressure to levels similar to levels in animals without endoleaks. This approach may be a strategy for future treatment of type II endoleaks.

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