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Biomedical subjects

Howard P Greisler

Publications and source records attributed to Howard P Greisler.

16 recordsLinked to original sources
PubMed2006

Improving endothelial healing with novel chimeric mitogens.

BACKGROUND: Chimeric proteins may be used to direct cell-specific activity. Heparin-binding growth-associated molecule (HBGAM) binds to cell receptors that are relatively more robust on endothelial cells, and it may confer endothelial cell selectivity to potent angiogens such as fibroblast growth factor-1 (FGF-1). METHODS: By ligating fibroblast growth factor or its potent mutant, S130K, to HBGAM, we tested their effect on re-endothelialization after angioplasty injury by using a canine model. RESULTS: Both HBGAM/S130K- and HBGAM/FGF-1-treated arteries had increased neointimal mitotic index and re-endothelialization rates at 30 days compared with control arteries without inducing a significant increase in the neointimal thickness or the ratio of neointimal to medial thickness between treatment and control groups. CONCLUSION: HBGAM/S130K and HBGAM/FGF-1 facilitates endothelial healing without myointimal thickening after canine carotid artery balloon angioplasty injury. Application of these growth factors in fibrin glue may improve endothelialization clinically after angioplasty or endarterectomy.

Animals↗
PubMed2006

Sustained low levels of fibroblast growth factor-1 promote persistent microvascular network formation.

BACKGROUND: Therapeutic neovascularization using high growth factor concentrations may lead to transient vessel formation and abnormal microvascular structure. The goal of this study was to quantify temporal and concentration effects of fibroblast growth factor-1 (FGF-1) on the persistence and morphology of microvascular networks. METHODS: Endothelial cells were incubated in suspension culture forming aggregates that were embedded in fibrin glue (FG) and stimulated with varying concentrations of FGF-1 with of heparin. Capillary networks formed were quantified for 21 days. RESULTS: High FGF-1 concentrations resulted in rapid and intense sprout formation, with excessive branching. At later times, these vessels regressed, with cellular debris in former vessel locations. At later times, the 1-ng/mL group surpassed the high concentration groups with continuous sprout growth and complete FG vascularization by 23 days. CONCLUSION: Sustained low levels of FGF-1 maintained a persistent microvascular network response, whereas higher levels resulted in abnormal phenotype followed by vessel regression.

Animals↗
PubMed2004

Heparin-independent mitogenicity in an endothelial and smooth muscle cell chimeric growth factor (S130K-HBGAM).

BACKGROUND: Through site-directed mutagenesis we have created a favorable fibroblast growth factor-1 (FGF-1) mutant (S130K) and linked it to a heparin-binding growth-associated molecule (HBGAM) to form the chimera S130K-HBGAM creating a heparin-independent, endothelial cell (EC)-specific mitogen. METHODS: The proliferative responses of primary canine carotid artery smooth muscle cells (SMC) and jugular vein EC to FGF-1, S130K, or S130K-HBGAM, with and without heparin (5 U/mL), was quantitated by measuring tritiated thymidine uptake over 24 hours and expressing the results as percent of positive control (20% fetal bovine serum [FBS]) for group comparison. RESULTS: Unlike FGF-1, both S130K and S130K-HBGAM are heparin-independent mitogens for EC and SMC. S130K-HBGAM was equivalent to FGF-1 with heparin at 6 nmol/L. S130K-HBGAM did not demonstrate relative EC specificity in this assay. CONCLUSIONS: At higher concentrations, S130K-HBGAM is a potent, heparin-independent EC and SMC mitogen. Co-culture assays and in vivo delivery models may demonstrate EC specificity not identified in this single cell type proliferation assay.

Analysis of Variance↗
PubMed2004

Same-evening discharge after carotid endarterectomy: our initial experience.

PURPOSE: The purpose of this study was to review the initial implementation of a same-evening discharge algorithm for patients undergoing carotid endarterectomy (CEA). METHOD: We conducted a retrospective review of a prospective database of patients undergoing CEA over 3 years. RESULTS: From January 2000 to December 2002, 207 patients underwent CEA, of which 186 qualified for same-evening discharge. Fifty-nine patients (32%) who qualified were discharged to home the same evening; none had an adverse event after discharge. The most common reason for patients not to be discharged the same evening was exiting the operating room too late (n = 63, 34%). Thirteen patients chose to stay overnight, and 11 patients did not go home secondary to physician choice. None of these patients experienced any adverse sequelae during the overnight stay. CONCLUSION: Same-evening discharge after CEA is safe and feasible in selected patients. Currently, nearly one third of our patients are discharged within 8 hours of CEA. With appropriate scheduling, patient education, and increasing physician awareness, most patients can be discharged to home the same evening after CEA.

Algorithms↗
PubMed2004

Silyl-heparin bonding improves the patency and in vivo thromboresistance of carbon-coated polytetrafluoroethylene vascular grafts.

OBJECTIVES: Our purpose was to improve the performance of carbon-coated expanded polytetrafluoroethylene vascular grafts by bonding the grafts with silyl-heparin, a biologically active heparin analog, using polyethylene glycol as a cross-linking agent. Material and method Silyl-heparin-bonded carbon-coated expanded polytetrafluoroethylene vascular grafts (Bard Peripheral Vascular, Tempe, Ariz), were evaluated for patency and platelet deposition 2 hours, 7 days, and 30 days after graft implantation in a canine bilateral aortoiliac artery model. Platelet deposition was determined by injection of autologous, (111)Indium-radiolabeled platelets, followed by a 2-hour circulation period prior to graft explantation. Histologic studies were performed on a 2-mm longitudinal strip of each graft (7-day and 30-day groups). Heparin activity of the explanted silyl-heparin grafts was determined by using an antithrombin-III based thrombin binding assay. RESULTS: Overall chronic graft patency (7-day and 30-day groups) was 100% for the silyl-heparin bonded (16/16) grafts versus 68.75% for control (11/16) grafts (P =.043). Acute 2-hour graft patency was 100% for the silyl-heparin bonded (6/6) grafts versus 83.3% for control (5/6) grafts. Radiolabeled platelet deposition studies revealed a significantly lower amount of platelets deposited on the silyl-heparin grafts as compared with control grafts in the 30-day group (13.8 +/- 7.18 vs 28.4 +/- 9.73, CPM per cm2 per million platelets, mean +/- SD, P =.0451, Wilcoxon rank sum test). In the 2-hour group of dogs, a trend towards a lower deposition of platelets on the silyl-heparin grafts was observed. There was no significant difference in platelet deposition between the two grafts in the 7-day group. Histologic studies revealed a significant reduction in intraluminal graft thrombus present on the silyl-heparin grafts as compared with control grafts in the 30-day group of animals. In contrast, there was no difference in amount of graft thrombus present on both graft types in the 7-day group of dogs. Pre-implant heparin activity on the silyl-heparin bonded grafts was 2.0 IU/cm(2) (international units[IU]/cm(2)). Heparin activity remained present on the silyl-heparin grafts after explantation at all 3 time points (2 hours: above upper limit of assay, upper limit = 0.57, n = 6; 7 days: 0.106 +/- 0.015, n = 5; 30 days: 0.007 +/- 0.001, n = 5; mean +/- SD, IU/cm(2)). CONCLUSION: Silyl-heparin bonding onto carbon-coated expanded polytetrafluoroethylene vascular grafts resulted in (1) improved graft patency, (2) increased in vivo graft thromboresistance, and (3) a significant reduction in intraluminal graft thrombus. This graft may prove to be useful in the clinical setting.

Animals↗
PubMed2004

Comparison of standard carotid endarterectomy with Dacron patch angioplasty versus eversion carotid endarterectomy during a 4-year period.

Currently, the two primary approaches to carotid endarterectomy for extracranial carotid stenosis are carotid endarterectomy with patch angioplasty and eversion carotid endarterectomy. In a retrospective study over a 4-year period from 1998 to 2002, we had an opportunity to compare the two approaches as two surgeons utilized carotid endarterectomy with Dacron patch angioplasty and two other surgeons utilized eversion carotid endarterectomy. During the 4-year period, 189 carotid endarterectomies were performed, 125 with Dacron patch angioplasty (CE-P) and 64 with eversion (EE) endarterectomy. There were no significant differences in age of the patients, operative indication, or associated risk factors between the two groups. Perioperative outcome measurement in the CE-P versus EE included stroke or transient ischemic attack, 1.6 per cent versus 1.56 per cent, cranial nerve injury, 2.4 per cent versus 3.13 per cent; death, 0.8 per cent versus 0 per cent; need for operative conversion or revision, 2.4 per cent versus 7.81 per cent, respectively. Only the need for operative conversion or revision reached significant difference (P < 0.05), although the need decreased to 4 per cent for the last 50 EE cases. Recurrent stenosis of 50 per cent to 79 per cent was 4.88 per cent versus 3.13 per cent and >80 per cent was 0.81 per cent versus 0 per cent in the CE-P versus EE group over a follow up of 16.3 months and 17.0 months, respectively. We conclude that both CE-P and EE are equally efficacious operative approaches to extracranial carotid occlusive disease.

Aged↗
PubMed2003

Silyl-heparin adsorption improves the in vivo thromboresistance of carbon-coated polytetrafluoroethylene vascular grafts.

BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) remains the most commonly utilized synthetic graft material for infrainguinal arterial reconstruction. However, patency rates of ePTFE bypass grafts are inferior to those observed with autogenous vein grafts. Modification of the luminal surface of ePTFE grafts such as coating with carbon or heparin, may prevent early graft failures and improve overall patency rates. We now report our results with a silyl-heparin adsorbed carbon-coated ePTFE graft. METHODS: Silyl-heparin was adsorbed onto carbon-coated ePTFE vascular grafts (Bard Peripheral Vascular, Tempe, Arizona), which were then evaluated for patency and platelet deposition acutely (2 hours after implantation) and 7 days after graft implantation in mongrel dogs. Dogs underwent bilateral aortoiliac grafting where one heparin adsorbed carbon-coated graft and one carbon-coated graft (control) were placed on either (alternating) side. Platelet deposition was determined by injection of autologous (111)Indium radiolabeled platelets followed by a 2-hour circulation period prior to explantation of grafts. Heparin activity of the silyl-heparin grafts (at preimplantation and explantation) was determined using an antithrombin-III based thrombin binding assay. RESULTS: Graft patency was 100% for both heparin coated (5 of 5) grafts and control (5 of 5) grafts in the acute group of dogs. In the 7-day group, patency was 87.5% for heparin coated (7 of 8) grafts and 50% for control (4 of 8) grafts (P = 0.28, Fisher's exact test). Radiolabeled platelet studies revealed a significantly lower deposition of platelets on heparin coated grafts compared with control grafts in the acute group (17.3 +/- 13.5 versus 35.2 +/- 17.9 counts per minute, per cm(2) per million platelets, mean +/- SEM; n = 5, P <0.05, paired Student t test). In the 7-day group of dogs with bilaterally patent grafts (4 of 8), a trend toward a lower deposition of platelets on heparin coated grafts compared with control grafts was observed (1.55 +/- 0.409 versus 2.14 +/- 1.13 counts per minute, per cm(2) per million platelets, mean +/- SEM; n = 4, P = 0.52, paired Student t test). Eight percent of the preimplantation heparin activity remained on the explanted silyl-heparin grafts after 2 hours and only 2% after 7 days. CONCLUSIONS: Silyl-heparin adsorption onto carbon-coated ePTFE vascular grafts resulted in improved acute thromboresistance in a canine bilateral aortoiliac model. Ongoing laboratory efforts are aimed at improving the silyl-heparin retention on vascular grafts. This graft may prove to be useful in the clinical setting.

Adsorption↗
PubMed2003

R136K fibroblast growth factor-1 mutant induces heparin-independent migration of endothelial cells through fibrin glue.

OBJECTIVES: R136K is a mutation of fibroblast growth factor-1 (FGF-1) in which arginine replaces lysine at the primary thrombin cleavage site. This may be important in vivo in inducing endothelial cell (EC) migration and coverage of arterial injury sites by allowing R136K to be used in a fibrin glue delivery system, without thrombin-induced degradation, in the absence of heparin. The objectives of this study were to determine whether R136K, with and without heparin, can induce migration of EC and smooth muscle cells (SMC) through fibrin glue, and to compare these results with those of wild-type FGF-1; and to determine the resistance of R136K to thrombin-induced degradation versus FGF-1. METHODS: The dose-response migration through fibrin glue induced by wild-type FGF-1 and the R136K mutant in the presence and absence of heparin was tested with EC and SMC. Migration was tested with 50, 100, and 200 ng/mL of both FGF-1 and R136K, either with or without 5 U/mL of heparin. Migration of EC was also assessed after growth inhibition with mitomycin C. A novel modified Boyden chamber-type migration assay using fibrin glue on the upper surface of the chamber filter was used to test migration. The fluorescent marker calcein was used to identify those cells that had migrated through the fibrin glue and were embedded in the filter. Molecular degradation by thrombin was assessed with sodium dodecylsulfate polyacrylamide gel electrophoresis. RESULTS: For EC, R136K in the absence of heparin induced significantly more migration than did FGF-1 at 50 (P <.002), 100 (P <.0001), and 200 (P <.0001) ng/mL. In the presence of heparin, a chemotactic response of EC to cytokine was seen at all doses, with no significant difference between FGF-1 and R136K. A dose-dependent difference was noted in this group between the 100 and 200 ng/mL concentrations of cytokine (for FGF-1, P <.0001; for R136K, P <.0001). SMC showed no difference in migration with FGF-1, R136K, or negative control at any dose in the presence or absence of heparin. Gel electrophoresis demonstrated that R136K was more resistant to thrombin degradation than was FGF-1. CONCLUSION: Site-directed mutagenesis of FGF-1 to R136K enables induction of heparin-independent migration of EC through fibrin glue at an optimal concentration of 100 ng/mL. Neither FGF-1 nor R136K elicits SMC migration through fibrin glue. The ability of R136K to induce EC migration through fibrin glue in the absence of heparin may prove useful in vivo by inducing EC migration and coverage of arterial injury sites, thus potentially reducing thrombogenicity and intimal hyperplasia.

Cell Division↗
PubMed2003

Biomaterials in the development and future of vascular grafts.

Recent developments in the field of tissue engineering have re-invigorated the quest for more suitable biomaterials that are applicable to novel cardiovascular devices, including small-diameter vascular grafts. This review covers both commercially available and relevant newly developed experimental materials, including elastic polymers (polyurethane), the biodegradable and bioresorbable materials, and the naturally occurring materials, focusing on their potential applications in the development of future vascular substitutes.

Biocompatible Materials↗
PubMed2003

Vascular grafts.

Autogenous vein is the conduit of choice in the surgical creation of bypasses of small-to-medium-caliber vessels in patients with peripheral occlusive arterial disease and will remain so for the near future. The success rate of bypasses using conduits of diameters greater than 6 mm has been excellent, whereas the majority of bypasses using smaller conduits fail within 5 years. In addition, due to a steep increase in rates of diabetes and decreasing cardiovascular mortality rates, increasing challenges are presented by this population. These facts have motivated much of the research in the cardiovascular arena over the past four decades, with improved techniques and new materials. Strategies to improve outcomes include the use of alternative materials including autologous, nonautologous and prosthetic grafts, utilizing different methods for their harvesting and preservation; tissue engineering, using either polymer- or biological-based scaffolds for cell seeding; endovascular methodologies; and gene therapy. This report presents an overview of the several options currently available in the management of patients with peripheral arterial occlusive disease, as well as the ongoing research directed towards the creation of an artificial engineered vessel, discussing experimental work in which endothelial cells have been seeded on different scaffolds and finally the potential application of gene therapy in the field of vascular reconstruction.

Arterial Occlusive Diseases↗
PubMed2002

Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system.

BACKGROUND: We have developed an in vitro 3-dimensional angiogenesis system in which the length, distribution, and ultrastructure of induced capillary sprouts were analyzed in response to concentration ranges of fibroblast growth factor (FGF)-1 and vascular endothelial growth factor (VEGF) and synergistic activity quantitated. METHODS: Bovine aorta endothelial cell aggregates were embedded in fibrin gel (FG) supported by a nylon mesh ring. The formed disks were cultured in 24-well plates in assay media. The test growth factors FGF-1, VEGF, or both (0 to 100 ng/mL) with 100 KIU/mL aprotinin were added to the media. The disks (n = 8/group) were digitally photographed and capillary sprouts quantitated. Assay disks were then fixed and sectioned for morphology. RESULTS: In aprotinin-stabilized FG, aggregated ECs invaded FG radially, forming sprouts and capillary networks. Neovessel lumens surrounded by ECs were confirmed on hematoxylin and eosin and transmission electron microscopy and by formation of cell junctions by transmission electron microscopy. The angiogenic effects of FGF-1 and VEGF were dose-dependent in the range from 1 to 100 ng/mL. Significant activity of FGF-1 started at 1 ng/mL and of VEGF at 2 ng/mL. The greatest effect was at the highest concentration (100 ng/mL) for both cytokines. The combination of 10 ng/mL of each FGF-1 and VEGF induced a significantly greater effect than the additive effects of FGF-1 (10 ng/mL) or VEGF (10 ng/mL) alone when analyzed with SAS system for mixed model (P <.0001), and that also exceeded the effects by 20 ng/mL of either FGF-1 or VEGF. CONCLUSIONS: A 3-dimensional capillary network can be induced in aprotinin-stabilized FG using FGF-1 or VEGF with synergism between the 2 angiogens.

Animals↗
PubMed2002

The effect of intraoperative duplex on the management of postoperative stroke.

BACKGROUND: Stroke after carotid endarterectomy (CEA) may be a result of intraoperative ischemia, embolism, or thrombosis at the operative site. Intraoperative duplex should eliminate the occurrence of a severe internal carotid artery (ICA) thrombosis and, thus, negate the benefit of reoperation. This article will detail the results of our evolving treatment algorithm for immediate versus delayed post-CEA neurologic deficit (ND). METHODS: We studied patients who had an ND after CEA from 1988 to 2000. Results. Thirty-two patients (3.2%) had a post-CEA ND (26 related stroke or transient ischemic attack, 6 other); 31 had a satisfactory intraoperative duplex post-CEA, 1 was not tested. Fifteen patients awoke from operation with a related deficit, 5 of whom were re-explored and all had a patent ICA. One patient without lateralizing signs who was not re-explored had extensive thrombosis at postmortem. The remaining 9 all had a duplex-proven patent ICA. Ten patients had a lucid interval before their related ND. Six patients were re-explored and all had thrombosed ICAs; 5 of the 6 improved postthrombectomy. Four patients were not re-explored for various reasons; a carotid thrombosis was not later diagnosed in any of these patients. CONCLUSIONS: Intraoperative and postoperative duplex has modified our treatment of post-CEA stroke. No longer are all patients re-explored. Patients with a normal intraoperative duplex who awaken with an immediate stroke do not usually have occlusive thrombus and routine re-exploration does not benefit these patients. Patients who have an ND develop after a lucid period may have a thrombosed ICA despite a normal intraoperative duplex, and unless there is a timely normal duplex, re-exploration is recommended and appears to benefit these patients.

Endarterectomy, Carotid↗
PubMedDate not supplied

Therapeutic neovascularization: contributions from bioengineering.

A number of pathological entities and surgical interventions could benefit from therapeutic stimulation of new blood vessel formation. Although strategies designed for promoting neovascularization have shown promise in preclinical models, translation to human application has met with limited success when angiogenesis is used as the single therapeutic mechanism. While clinical protocols continue to be optimized, a number of exciting new approaches are being developed. Bioengineering has played an important role in the progress of many of these innovative new strategies. In this review, we present a general outline of therapeutic neovascularization, with an emphasis on investigations using engineering principles to address this vexing clinical problem. In addition, we identify some limitations and suggest areas for future research.

Angiogenesis Inducing Agents↗