Biomedical subjects

Scott Hollenbeck

Publications and source records attributed to Scott Hollenbeck.

10 recordsLinked to original sources

PubMed2005

Rapamycin inhibits fibronectin-induced migration of the human arterial smooth muscle line (E47) through the mammalian target of rapamycin.

The matrix protein fibronectin (FN) is a potent agoinst of vascular smooth muscle cell (SMC) migration. The role of rapamycin and the mammalian target of rapamycin (mTOR) in matrix protein-induced migration has not yet been defined. In these studies, we found that rapamycin (10 nM) markedly diminished chemotaxis of E47 cells (a cell line derived from human atherosclerotic plaques) and rat aortic SMCs toward FN as well as type I collagen and laminin; however, a period of preincubation >20 h was required. Subsequently, we showed that treatment with FN induced a rapid activation of mTOR as well as its downstream effector, S6 kinase (S6K). Moreover, FN-induced activation of both proteins was inhibited by preincubation with rapamycin for only 30 min. We then explored the upstream signaling pathway through which FN might mediate mTOR activation. A blocking antibody to alpha(v)beta(3) inhibited FN-induced mTOR/S6K activation as well as E47 cell chemotaxis, implicating alpha(v)beta(3) as the integrin receptor responsible for initiating FN-induced migration. Moreover, preincubation of E47 cells with wortmannin or LY-294002 blocked FN-induced mTOR/S6K activation, demonstrating that phosphatidylinositol 3-kinase (PI3K) plays a critical role in this rapamycin-sensitive signaling pathway. It has been previously suggested that rapamycin's effect on migration maybe related to enhancement of p27(kip1). However, treatment of E47 cells with rapamycin did not alter the level of p27(kip1) in the presence or absence of FN. Taken together, our data demonstrate that rapamycin inhibits FN-induced SMC migration through a pathway that involves at least alpha(v)beta(3)-integrin, PI3K, mTOR, and S6K.

Androstadienes↗

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

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↗

PubMed2004

Continuity in the treatment of carotid artery disease: results of a carotid stenting program initiated by vascular surgeons.

The treatment of carotid artery stenosis currently constitutes a major component of vascular surgical practice. Carotid angioplasty and stenting (CAS), however, is mainly performed by nonvascular surgeon interventionalists with cerebral protection devices available only through investigational protocols. This study reports the initial results of a CAS program initiated and performed by vascular surgeons using commercially available cerebral protection devices. Fifty-seven patients were enrolled in the study over a 14-month period. All patients were at high risk for conventional endarterectomy (7 resentosis, 4 irradiation, and 46 medically high-risk ASA III). Mean age was 75.7 years (range, 45-93 years). High-grade stenosis of the carotid artery was present in all cases (mean stenosis, 85%; range, 80-99%). Twenty-four percent of patients were symptomatic. Cerebral protection was performed with an occlusion balloon-wire in 32 cases and with a filter-wire device in 24; no cerebral protection was used in 1 patient with restenosis after endarterectomy. Initially in the study, atropine was administered selectively for the development of bradycardia. Currently atropine is administered routinely prior to the initial balloon angioplasty of the carotid bulb. Clopidogrel (75 mg/day) was administered for 5 days prior to CAS and for 30 days after CAS. All 57 patients underwent successful dilatation of their carotid stenoses without occlusion or dissection. Ten of 32 patients in whom balloon occlusion was used for cerebral protection exhibited transient evidence of cerebral ischemia during protection balloon occlusion. These symptoms resolved completely without permanent neurological deficit in all cases. Development of bradycardia with a heart rate <50 bpm was significantly reduced by routine administration of atropine prior to the initial dilatation within the carotid bulb (p = 0.01). Mean hospital length of stay was 1.33 days (range, 1-5 days). There were two periprocedure myocardial infarctions, two postprocedure transient ischemic attacks, and one reversible ischemic neurologic deficit. There was no 30-day mortality. There have been no instances of hemodynamically significant restenosis during a mean follow-up period of 5.4 months. From these results we have concluded that CAS can be performed effectively and safely using commercially available cerebral protection devices. A program initiated and performed exclusively by vascular surgeons is effective and should be the standard model used in the endovascular treatment of carotid artery stenosis.

Aged↗

PubMed2004

Characterization of retrograde collateral (type II) endoleak using a new canine model.

OBJECTIVE: The clinical significance of retrograde collateral arterial perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) has not been completely characterized. In this study a canine model was used to analyze intra-aneurysmal pressure, thrombus histologic characteristics, endoleak patency, and radiographic appearance of type II endoleaks originating from single and multiple aneurysm side branches. METHODS: Prosthetic aneurysms with an intraluminal solid-state strain-gauge pressure transducer were created in the infrarenal aorta of 14 mongrel dogs. A single collateral side branch was reimplanted in 4 animals, multiple side branches were reimplanted in 6 animals, and no side branches were reimplanted in 4 control animals. Intra-aneurysmal and systemic pressure was measured for 60 to 90 days after creation of the type II endoleak. Endoleak patency and flow were assessed with duplex ultrasound scanning and cine-magnetic resonance angiography. Histologic analysis of the intra-aneurysmal thrombus was also performed. RESULTS: Stent-graft exclusion reduced intra-aneurysmal pressure significantly in all animals, as compared with systemic pressure (P < .001). All intra-aneurysmal pressure values are indexed to the systemic pressure, and are represented as a percentage of the simultaneously obtained systemic pressure, which has a value of 1.0. Type II endoleaks originating from multiple side branches exhibited significantly increased intra-aneurysmal systolic pressure, mean pressure, and pulse pressure, as compared with endoleaks derived from either a single side branch (systolic pressure: multiple, 0.70 +/- 0.28 vs single, 0.50 +/- 0.19; P < .001; mean pressure: multiple, 0.78 +/- 0.23 vs single, 0.59 +/- 0.22, P < .001; pulse pressure: multiple, 0.41 +/- 0.25 vs single, 0.17 +/- 0.15, P < .001) or excluded control aneurysms that had no side branches and no endoleak (systolic pressure, 0.17 +/- 0.09; mean pressure, 0.14 +/- 0.10; pulse pressure, 0.098 +/- 0.08; P < .001). Cine-magnetic resonance angiograms and duplex ultrasound scans documented persistent patency of multiple branch endoleaks up to the time of euthanasia. In contrast, single side branch endoleaks thrombosed within 3 days (P < .001). Thrombus in the aneurysm sac in close proximity to the endoleak contained intact red blood cells and limited fibrin. Thrombus distant from the endoleak demonstrated extensive fibrin deposition and degraded red blood cells. CONCLUSION: The canine model may be used to reliably measure intra-aneurysmal pressure in the presence of patent and thrombosed type II endoleaks. In this model 2 or more side branches are necessary to maintain persistent patency of type II endoleaks. These endoleaks are associated with significantly elevated intra-aneurysmal pressure, that is, 70% to 80% of systemic pressure. These results suggest that persistent type II endoleaks have clinical significance. CLINICAL RELEVANCE: Endoleaks originating from retrograde flow in the side branch vessels of the aneurysm generate significant levels of intra-aneurysmal pressure, that is, 70% to 80% of systemic pressure. At least 2 patent side branch vessels appear to be necessary to cause persistent patency of type II endoleak in the canine model. Further studies will be necessary to enable more complete characterization of retrograde endoleaks and to extend these findings to allow clinical application. However, these results suggest that persistently patent type II endoleaks are clinical significance and may require more intensive follow-up intervention.

Anastomosis, Surgical↗

PubMed2004

Computer simulation as a component of catheter-based training.

INTRODUCTION: Computer simulation has been used in a variety of training programs, ranging from airline piloting to general surgery. In this study we evaluate the use of simulation to train novice and advanced interventionalists in catheter-based techniques. METHODS: Twenty-one physicians underwent evaluation in a simulator training program that involved placement of a carotid stent. Five participants were highly experienced in catheter-based techniques (>300 percutaneous cases), including carotid angioplasty and stenting (CAS); the remaining 16 participants were interventional novices (<5 percutaneous cases). The Procedicus VIST simulator, composed of real-time vascular imaging simulation software and a tactile interface coupled to angiographic catheters and guide wires, was used. After didactic instruction regarding CAS and use of the simulator, each participant performed a simulated CAS procedure. The participant's performance was supervised and evaluated by an expert interventionalist on the basis of 50 specific procedural steps with a maximal score of 100. Specific techniques of guide wire and catheter manipulation were subjectively assessed on a scale of 0 to 5 points based on ability. After evaluation of the initial simulated CAS procedure, each participant received a minimum of 2 hours of individualized training by the expert interventionalist, with the VIST simulator. Each participant then performed a second simulated CAS procedure, which was graded with the same scale. After completion, participants assessed the training program and its utility via survey questionnaire. RESULTS: The average simulated score for novice participants after the training program improved significantly from 17.8 +/- 15.6 to 69.8 +/- 9.8 (P < .01), time to complete simulation decreased from 44 +/- 10 minutes to 30 +/- 8 minutes (P < .01), and fluoroscopy time decreased from 31 +/- 7 minutes to 23 +/- 7 minutes ( P < .01). No statistically significant difference in score, total time, or fluoroscopy time was noted for experienced interventionalists. Improvement was noted in guide wire and catheter manipulation skills in novices. Analysis of survey data from experienced interventionalists indicated that the simulated clinical scenarios were realistic and that the simulator could be a valuable tool if clinical and tactile feedback were improved. Novices also thought the simulated training was a valuable experience, and desired further training time. CONCLUSIONS: An endovascular training program using the Procedicus VIST haptic simulator resulted in significant improvement in trainee facility with catheter-based techniques in a simulated clinical setting. Novice participants derived the greatest benefit from simulator training in a mentored program, whereas experienced interventionalists did not seem to derive significant benefit.

Blood Vessel Prosthesis Implantation↗

PubMedDate not supplied

Rupture of excluded popliteal artery aneurysm: implications for type II endoleaks--a case report.

The fate of popliteal artery aneurysms after ligation and bypass is believed to be relatively innocuous. The patient presented in this report, however, experienced spontaneous rupture of a popliteal aneurysm 11 years after ligation and bypass. Magnetic resonance angiography was used to establish the diagnosis of rupture, which was subsequently confirmed at surgery. Intraoperative arteriography demonstrated persistent collateral arterial perfusion of the excluded popliteal aneurysm sac. The collateral arterial flow originated from the superior and inferior lateral genicular arteries. The persistent arterial perfusion resulted in growth of the aneurysm from 4.2 to 7.0 cm over the 11-year period. The ruptured aneurysm was successfully treated by direct arterial exposure and suture ligation of the collateral vessels performed from within the aneurysm sac. The development of popliteal aneurysm expansion and rupture as a result of collateral arterial perfusion suggests that persistent collateral perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) may lead to aneurysm rupture. Therefore, close observation and intervention for aneurysm expansion to prevent rupture of the excluded aneurysm are warranted.

Aged↗

PubMedDate not supplied

Postcarotid endarterectomy pseudoaneurysm treated with combined stent graft and coil embolization--a case report.

Pseudoaneurysm formation is a rare complication following carotid endarterectomy (CEA); however, its occurrence is associated with significant risk of morbidity. The patient in this report presented 2 years following CEA with headache and lateral neck mass. The diagnosis of a 3.5 x 3.0 cm carotid artery bifurcation pseudoaneurysm was made by using magnetic resonance angiography (MRA). Endovascular exclusion of the aneurysm was accomplished with coil embolization of the external carotid artery followed by deployment of a 7 x 50 mm wall stent graft into the common carotid artery-internal carotid artery (CCA-ICA). The patient's symptoms improved and at 6-months postexclusion, duplex ultrasound demonstrated a significant reduction in pseudoaneurysm size. This case highlights the feasibility and safety of using endovascular techniques in the treatment of post-CEA pseudoaneurysm.

Aged↗

PubMedDate not supplied

Endoluminal recanalization in a patient with phlegmasia cerulea dolens using a multimodality approach-a case report.

Phlegmasia cerulea dolens is a limb-threatening form of deep venous thrombosis and should be treated aggressively. The authors report a patient who presented with iliocaval and femoral deep venous thrombosis and posed an additional therapeutic challenge based on a recent history of heparin-induced thrombocytopenia. Catheter-directed pharmacologic thrombolysis and balloon venoplasty were applied in treatment. The direct thrombin inhibitor argatroban was used in place of heparin for concurrent anticoagulation. This multimodality endovascular approach (chemical and mechanical interventions) was successful in relieving the venous occlusion and salvaging the limb, while maintaining appropriate treatment for heparin-induced thrombocytopenia.

Anticoagulants↗

PubMedDate not supplied

Experimental analysis of transvenous ultrasonography in localizing and grading renal artery stenosis.

This study evaluated the potential for transvenous ultrasonography to assess renal artery stenosis (RAS), the most common correctable cause of hypertension in the United States. We developed a porcine model for studying RAS using TVUS. An endovascular ultrasound probe was placed into the inferior vena cava and renal veins to image renal arteries in which stenoses had been surgically created in varied locations and to varied degrees. TVUS was then used to identify and assess these stenotic lesions. The accuracy of TVUS for determining the degree and location of the stenoses was then determined using contrast arteriography as the standard. When compared with arteriography, TVUS identified and properly located all six lesions and correctly quantified the degree of stenosis in five of the six lesions. TVUS is an effective means of assessing the presence, degree, and location of stenotic lesions of the renal arteries in this animal model. Study of this method in humans may be warranted.

Animals↗