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Biomedical subjects

J C Palmaz

Publications and source records attributed to J C Palmaz.

At least 19 recordsLinked to original sources

Fibrinogen: structure, function, and surface interactions.

Fibrinogen plays a central role in the mechanism of coagulation and thrombosis and is partially involved in the development of postintervention restenosis. Because of therapeutic implications, it is convenient for the vascular interventionalist to revisit its structure, function, and relationships within the vascular environment. This review focuses on the molecular structure, mechanisms of polymerization and lysis, and fibrinogen interaction with the platelet alpha(IIb)beta(3) [corrected] integrin. It also addresses the less understood interaction of fibrinogen with artificial surfaces. Glycoprotein IIb-IIIa blockers, targeted to interfere with fibrinogen-platelet interactions, widely used in clinical practice, are discussed, and trials of new drugs are also summarized.

Fibrinogen↗

Influence of stent edge angle on endothelialization in an in vitro model.

PURPOSE: To investigate the influence of topographic features in the path of migrating endothelial cells, specifically the effect of edge angle of intravascular metallic material on endothelialization. MATERIALS AND METHODS: Flat 1-cm x 1-cm 316-L pieces of stainless steel were placed on confluent monolayers of human aortic endothelial cells. The thickness of each metal piece was ground to achieve an edge angle of 35 degrees, 70 degrees, 90 degrees, or 140 degrees (n = 6 each) in relation to the endothelial surface. Migration distance and density of endothelial cell coverage on the metal pieces were measured in groups of six each under static conditions at 4, 7, and 11 days and flow conditions (16 dynes/cm(2)) at 4 days. RESULTS: Endothelial cell migration distance along the surface of the pieces with edge angles of 35 degrees was significantly greater than that with those with larger angles (P < .05) under static and flow conditions. The migration distances on the 35 degrees piece were 87.5%, 47.3%, 57.1%, and 66.1% greater than those on the 90 degrees piece at the upstream, downstream, right, and left edges, respectively. There were no significant differences in cell density among different angle groups under flow or static conditions. CONCLUSION: The edge angle of intravascular metallic material has an influence on the rate of endothelialization. A smaller edge angle facilitates endothelialization over metallic material when compared to a larger angle. These results demonstrate the importance of metallic stent profile on endothelialization rate.

Cell Movement↗

Transjugular intrahepatic portosystemic shunt: accuracy of helical CT angiography in the detection of shunt abnormalities.

PURPOSE: To determine the sensitivity, specificity, and accuracy of helical computed tomographic (CT) angiography in the detection of transjugular intrahepatic portosystemic shunt (TIPS) stenoses or occlusions. MATERIALS AND METHODS: Thirty-seven patients underwent 50 helical CT angiographic examinations and, within 2 weeks of each examination, portography with measurement of the portosystemic pressure gradient. Helical CT angiograms were independently interpreted by three radiologists who were blinded to the results of portography. Results of helical CT angiography and portography were compared. Sensitivity and specificity of helical CT angiography were separately calculated for the demonstration of morphologic abnormalities and the determination of their hemodynamic significance. RESULTS: Of the 50 portograms, 31 (62%) demonstrated morphologic TIPS abnormalities, 24 (77%) with and seven (23%) without elevated portosystemic pressure gradients. Helical CT angiograms correctly demonstrated 30 (97%) of the 31 morphologic abnormalities and allowed correct diagnosis of 22 (92%) of the 24 hemodynamically significant abnormalities. Nineteen (38%) portograms were normal; helical CT angiograms correctly demonstrated the absence of abnormality in 17 (90%) of these cases. Sensitivity and specificity of helical CT angiography for all morphologic abnormalities were 97% and 89%, respectively, and, for hemodynamically significant abnormalities, 92% and 77%. CONCLUSION: Helical CT angiography holds promise as a screening modality for the detection of TIPS stenoses or occlusions.

Adult↗

Electrostatic forces on the surface of metals as measured by atomic force microscopy.

Electrostatic forces play an important role in modulating the interaction of plasma proteins and blood cellular components with the surface of the vascular endothelium. Based on the concept that electrostatic forces residing on the surface of metal intravascular prostheses, such as the stent, also are critical in influencing blood interactions with those surfaces and the vascular wall, these studies were designed to measure these forces on 4 metals using atomic force microscopy (AFM). AFM measurements performed in a low saline aqueous medium at physiological pH indicate a similar net electronegative surface charge level for gold and 316l stainless steel that is significantly higher than the level measured on an electropolished Nitinol surface. Heat oxidation of the Nitinol surface increased the overall electronegativity and created a more homogeneous surface charge distribution. This study demonstrates that AFM force measurements can be a valuable approach to understanding the electrostatic surface of metallic as well as other biomaterials that may be important in understanding how these surfaces influence vascular healing at intravascular interventional sites.

Biocompatible Materials↗

Protein interactions with endovascular prosthetic surfaces.

Blood protein interaction with prosthetic surfaces seems to be the initial step in the chain of events leading to tissue incorporation of endovascular devices. This paper focuses on the relationship between surface free energy and protein adsorption on metals and polymers commonly used for fabricating vascular prosthetic devices. Our results support a relationship between surface energy and protein adsorption. Albumin was more easily eluted than fibrinogen and fibronectin from most metals and all polymeric surfaces considered. Following elution, metals retained a larger fraction of protein as compared to polymers.

Albumins↗

Influence of topography on endothelialization of stents: clues for new designs.

To evaluate the influence of stent design on endothelialization of the stented surface, we placed trapezoidal objects of variable thickness on a confluent culture of endothelial cells and subjected the assembly to flow and shear conditions similar to those found in arteries. After 24 h, we measured and analyzed the area on top of the objects covered by cells and the maximum migration distance from the borders. In addition, we evaluated areas devoid of cells surrounding the objects, which developed after exposure of the assembly to flow. The cell-covered area and migration distance significantly decreased on objects 75 microns thick, and it was nonexistent on objects 250 microns thick. Areas devoid of cells or gaps were largest adjacent to the downflow side of the object, disposed transversely to flow. Cell gaps were smallest along the side aligned with flow. In conclusion, endothelial cell coverage may be impaired by stent wall thickness larger than 75 microns. It is likely that this impairment is related to flow disturbances impairing cell attachment.

Cell Movement↗

Blood flow and thrombus formation determine the development of stent neointima.

To establish a relationship between flow, acute thrombus formation, and late intimal formation in implanted arterial stents, canine femoral arteries with normal blood flow were compared to contralateral femoral arteries with restricted blood flow. Thrombocyte activity over the stent segment was evaluated for 3 h after stent placement with nuclear scanning, following administration of In-111 labeled platelets. To evaluate long-term stent patency in relationship to arterial flow, an additional group of dogs were subjected to long-term observation. Matched, symmetrically implanted femoral stents with normal and restricted flow were explanted at 1, 12, and 24 weeks for histological analysis and comparative measurement of neointimal thickness. Angiographic studies were performed before and after nuclear scan in the acute animals and before explant in the chronic animals. Acutely, heparinization prevented subocclusive or occlusive thrombus, regardless of flow. In the absence of heparinization, normal arterial blood flow did not prevent thrombus formation on stents. Chronically, stents with flow restriction had significantly greater neointimal formation in comparison with unrestricted stents. Histological studies suggested that the stent neointima resulted from progressive replacement of stent thrombus.

Angiography↗

Endothelial cell migration onto metal stent surfaces under static and flow conditions.

Restenosis associated with intimal hyperplasia and thrombosis at sites of balloon angioplasty or stent placement remains an important clinical problem. It is likely that loss or damage to the arterial endothelium associated with these interventional procedures as well as the rate of its restoration plays a critical role in the extent of restenosis. Migration of arterial endothelial cells from adjacent intact endothelium is the predominant source of cells involved in re-endothelialization of the injured site. In this paper, we review the influence of hemodynamics on endothelial cell migration, both in vivo and in vitro. In addition, we present recent in vitro studies demonstrating the importance of the nature of metal substrates in modulating endothelial cell migration rate. Finally, we review the cellular and molecular mechanisms likely involved in governing endothelial cell migration, and relate them to a possible scenario of endothelial response to injury at sites of arterial intervention. Understanding the important factors regulating endothelial migration may provide insights that will ultimately lead to methods to accelerate endothelial healing and reduce the occurrence of arterial restenosis.

Angioplasty, Balloon, Coronary↗

Influence of surface topography on endothelialization of intravascular metallic material.

PURPOSE: To determine whether grooves on a metal surface help endothelialization and, furthermore, what groove size is more likely to promote the fastest endothelialization in an in vitro model. Hypothetically, a microscopic pattern of parallel grooves disposed in the direction of flow, on the inner surface of stents, increases endothelial cell migration rates, resulting in decreased time to total coverage of the prosthetic surface. MATERIALS AND METHODS: Square, flat pieces of nitinol were placed level on a monolayer, confluent culture of endothelial cells. The metal pieces were treated to produce parallel grooves on the surface of 1, 3, 15, and 22 microm to be compared to polished, smooth controls. Microscopy images were obtained by digital capture and processed for analysis of migration distance and cell count, density, shape, and alignment. RESULTS: Grooved surfaces promoted increased rate of migration of endothelial cells, up to 64.6% when compared to smooth, control surfaces. Larger grooves resulted in greater migration rates. The cells aligned with the grooves, elongated, and become more numerous on grooved surfaces, particularly with large grooves. CONCLUSION: A pattern of microscopic parallel grooves more than doubles the migration rate of endothelial cells over metallic surfaces ordinarily used for endovascular stents. Future research in this area is aimed at demonstrating the potential effect of grooved endovascular stent surfaces on faster endothelialization times.

Alloys↗

Relationship between blood flow, thrombus, and neointima in stents.

PURPOSE: To establish a relationship between flow, acute thrombus formation, and late intimal hyperplasia in arterial stents. MATERIALS AND METHODS: To compare short-term stent patency in the canine femoral artery with normal flow to that in the opposite femoral artery with restricted flow, 24 dogs were subdivided in four groups: groups 1 (no intravenous heparin) and 2 (intravenous heparin) had unilateral flow restriction by surgically created stenosis, downstream of a Palmaz stent. Group 3 (no intravenous heparin) and 4 (intravenous heparin) had sham surgical exposure of the corresponding arterial segment, without flow restriction. Thrombocyte activity over the stent segment was evaluated for 3 hours after stent placement with nuclear scanning, after administration of indium-111-labeled platelets. To evaluate long-term stent patency in relationship to arterial flow, 14 additional dogs were subjected to long-term observation. Matched, symmetrically implanted femoral stents with normal and restricted flow, were explanted at 1, 12, and 24 weeks for histologic analysis and comparative measurement of neointimal thickness. Angiographic studies were performed before and after nuclear scanning in the short-term study group and before explant in the long-term animal group. RESULTS: In the short-term, groups 2 and 4 showed neither increased platelet uptake nor angiographically demonstrable thrombus. Group 1 had increased platelet uptake and occlusive or subocclusive angiographic thrombus. Group 3 had increased platelet uptake and angiographic thrombus in one instance. In the long-term, stents with flow restriction had significantly greater neointimal formation in comparison with unrestricted stents. Histologic studies suggested that the stent neointima resulted from progressive replacement of stent thrombus. CONCLUSION: Regardless of flow condition, intravenous heparinization is necessary to prevent thrombus formation in the stent lumen. Within the experimental parameters of this study, low flow and absent heparinization consistently lead to stent thrombosis. Stent implantation under low flow is associated with increased neointima formation. It is not known whether this is preventable by antithrombotic medication.

Animals↗

Polytetrafluoroethylene-encapsulated stent-grafts: use in experimental abdominal aortic aneurysm.

PURPOSE: To evaluate expanded polytetrafluoroethylene (ePTFE) encapsulated stents for the treatment of aortic aneurysms with emphasis on the blood and tissue-material interactions. MATERIALS AND METHODS: Experimental aortic aneurysms were created in dogs by enlarging the aortic lumen with an abdominal fascial patch. Twenty animals underwent endoluminal repair after allowing the surgically created aneurysm to heal for 2 months prior to transluminal aneurysmal exclusion. The device used consisted of an 8-cm-long ePTFE encapsulated stent graft. The animals were killed in groups at 1 week and at 1, 2.25, 6, and 12 months. Specimens were processed for histologic and luminal surface studies. RESULTS: Before the animals were killed, aortography demonstrated two thrombosed aortae in the 6-month group and two endoleaks in the 12-month group. Endothelialized neointima extended into the proximal and distal portions of the prosthetic lumen, with minimal cell coverage in the center of the graft. The overall percent surface area covered by endothelialized neointima was 22% +/- 6% at 6 months and 18% +/- 10% by 1 year (P = .75). Histologic examination demonstrated minimal tissue penetration into the ePTFE. CONCLUSION: Transluminal exclusion of abdominal aortic aneurysms by encapsulated stent-graft is easily accomplished. With this device, tissue coverage and penetration of the stent graft is limited and does not tend to increase with time.

Animals↗

Transjugular intrahepatic portosystemic shunts: assessment with helical CT angiography.

To evaluate diagnostic computed tomographic (CT) angiograms of transjugular intrahepatic portosystemic shunts (TIPS), helical CT angiography was performed in 10 patients with (n = 7) or without (n = 3) shunt dysfunction. CT angiography was performed with 3-mm-thick sections, pitch of 1, 120 kV, and 180-220 mA, after injection of 150 mL nonionic contrast material at 5 mL/sec, with a 50-second scanning delay after initiation of injection. All patients underwent transjugular portography within 1 week after CT angiography. In all cases, CT angiography correctly showed the presence or absence of the abnormality. These preliminary data suggest that CT angiography can provide diagnostic images of normal and abnormal TIPS.

Adult↗

New advances in endovascular technology.

Future research on and development of intravascular stents, stent grafts, and other implantable devices will be aimed largely at improving their blood and tissue biocompatibility. Most of the modifications resulting from this research and development will alter the surface properties we currently understand: surface energy or "wetability," electrical surface charge, surface texture, and surface chemistry. However, as knowledge of the physical, chemical, and biological properties of bioprosthetic surface materials expands, new areas for exploration will develop, increasing the opportunities for improvement.

Angioplasty, Balloon, Coronary↗

Aortoiliac aneurysms: management with endovascular stent-graft placement.

PURPOSE: To evaluate endovascular stent-graft placement for management of aortoiliac aneurysms. MATERIALS AND METHODS: Balloon-expandable stents covered with polytetrafluoroethylene were placed in 11 aortoiliac lesions in nine male non-surgical candidates (mean age, 63.5 years). There were six abdominal aortic aneurysms, four iliac artery aneurysms, and one acute pseudoaneurysm from a ruptured iliac artery. Stent-grafts were dilated up to 14 mm (iliac) and 24 mm (aorta). Patients underwent follow-up computed tomography and angiography. RESULTS: Stent-grafts were successfully placed in all 11 cases. There were two complications: a ruptured iliac artery treated with placement of an additional covered stent and a lower-extremity vessel embolization and bowel infarction resulting in death. All stent-grafts remained patent without increased aneurysmal diameter. Three leaks (27%) were detected. Two leaks were treated with placement of additional covered stents. One still is asymptomatic. CONCLUSION: Endovascular treatment of aortoiliac aneurysms with stent-graft devices may be an alternative to surgery.

Aged↗

Improvement of thrombocytopenia due to hypersplenism after transjugular intrahepatic portosystemic shunt placement in cirrhotic patients.

Thrombocytopenia secondary to hypersplenism is a well-known complication of portal hypertension. The effects of transjugular intrahepatic portosystemic shunt (TIPS) on hypersplenism have not been adequately studied. In this report, we describe 11 patients who had significant improvement in their thrombocytopenia due to hypersplenism after TIPS. There was a statistically significant improvement in the platelet counts after TIPS placement, in virtually every case during the follow-up period, although some patients had platelet counts less than 100,000/mm3 at the end of the follow-up period. Statistically significant hemodynamic improvement in the gradient pressure was observed immediately after TIPS. Furthermore, all patients tolerated the procedure well, and TIPS-related complications were encountered during the follow-up period. Our data suggest that TIPS is an effective, noninvasive alternative to surgical interventions in the management of hypersplenism in cirrhotic patients, who are generally high-risk surgical candidates.

Adult↗

Dissection of the external iliac artery in highly trained athletes.

We report a series of four acute external iliac artery dissections occurring in three patients within days of completion of ultraendurance athletic events. Acute dissection of the external iliac artery in highly trained athletes after competition has not been previously documented. A retrospective review of three cases was performed with subsequent follow-up, including imaging and hemodynamic measurements. Dissection was suspected on the basis of duplex imaging results in one case, and arteriography confirmed dissection in all cases. All patients were endurance athletes over the age of 40 years. One patient was found to have bilateral lesions. Treatment in two cases was initiated with percutaneous transluminal angioplasty, one with a successful result and subsequent Plamaz stent placement. In the other case percutaneous transluminal angioplasty was unsuccessful, and operative repair was required with the placement of a graft. The final patient who had bilateral involvement was treated conservatively. At a mean follow-up of 32 months, there have been no complications, and all patients have normal resting hemodynamics. Follow-up duplex imaging shows healing of the dissections in the untreated patient. Histopathologic study in the patient treated with operation disclosed dissection in an otherwise normal arterial wall. Highly trained athletes over the age of 40 are susceptible to external iliac artery dissection, and successful treatment has been achieved by surgical, endovascular, and conservative therapies.

Acute Disease↗