Biomedical subjects

H P Greisler

Publications and source records attributed to H P Greisler.

At least 19 recordsLinked to original sources

PubMed1997

Platelet deposition on ePTFE grafts coated with fibrin glue with or without FGF-1 and heparin.

INTRODUCTION: The disappointing long-term patency of small-caliber prosthetic grafts may be due in part to early thrombogenicity of the prosthetic surface. We previously reported that the coating of expanded polytetrafluoroethylene (ePTFE) with fibrin glue (FG) containing fibroblast growth factor type 1 (FGF-1) and heparin accelerated spontaneous endothelial coverage of ePTFE grafts in an animal model; however, FG's effect on platelets remains unclear. This study was done to evaluate platelet deposition onto GF/FGF-1/ heparin-coated vs FG-coated vs whole-blood-preclotted ePTFE surfaces. METHODS: Twelve 5-cm ePTFE grafts were treated either with FG (thrombin, 0.32 U/ ml, and fibrinogen, 32.1 mg/ml, n = 8) or with FG containing FGF-1 (11 ng/ml) plus heparin (250U/ml, n = 4). Twelve control ePTFE grafts were preclotted with canine (n = 8) or human (n = 4) whole blood. These treated grafts were placed onto a loop pulsatile perfusion system in pairs (preclotted with either FG or FG/ FGF-1/heparin) and perfused with a M-199/10% FBS/ 111indium-labeled platelet suspension. After 60 min the grafts were gamma counted and CPM/mm2 were determined. RESULTS: In both trials, the preclotted ePTFE grafts demonstrated similarly increased platelet deposition when compared to grafts treated with FG/FGF-1/heparin or FG alone (P < 0.001 for each). CONCLUSION: The decrease in platelet deposition on the FG/FGF-1/ heparin-coated grafts vs preclotted grafts is not due to heparin and is not specific to canine or human platelets. FG-coated grafts may induce a decrease in early graft thrombogenicity when compared to whole blood preclotting.

Animals↗

PubMed1997

Fibrin glue containing fibroblast growth factor type 1 and heparin decreases platelet deposition.

BACKGROUND: The early success rates of endarterectomy and angioplasty are influenced by the thrombogenicity of the deendothelialized surface. We previously reported decreased platelet deposition after 30 and 120 minutes and after 28 days on expanded polytetrafluoroethylene (ePTFE) grafts coated with fibrin glue (FG) containing fibroblast growth factor type 1 (FGF-1) and heparin in canine aortoiliac bypass grafts when compared with control uncoated grafts. The FG/FGF-1/heparin coating has been shown to enhance spontaneous endothelialization at 28 days in canine ePTFE bypass grafts. The current study evaluates the thrombogenicity of this FG/FGF-1/heparin suspension applied to a balloon de-endothelialization model of endarterectomy in canine carotid arteries. METHODS: Nine dogs underwent bilateral, deendothelialization balloon injury to 6-cm segments of their carotid arteries. Fibrin glue (fibrinogen 32.1 mg/mL + thrombin 0.32 U/mL) containing FGF-1 (11 ng/mL) and heparin (250 U/mL) was applied to the luminal surface of one carotid artery in each dog. Both femoral arteries were circumferentially dissected but not balloon injured; one femoral artery was clamped for the same period as the carotid arteries. In the 6 acute dogs, 10 minutes prior to the restitution of flow in both carotid arteries and one femoral artery, 4 to 8 x 10(9) (111)In-labelled autologous platelets were injected intravenously. Four-cm segments of both carotid and femoral arteries were excised after 15 or 120 minutes of circulation (n = 3/time/artery, 24 arteries). In the 3 chronic dogs, the radiolabelled platelets were injected 30 days after carotid injury. The carotid and femoral vessels were then excised after 120 minutes of perfusion. Radioactive platelet deposition was quantitated by gamma counting. RESULTS: After 2 hours, the injured carotid arteries demonstrated significantly more platelet deposition than either uninjured femoral artery controls (P < 0.001). There was also a significant 45.2% decrease (P = 0.008) in platelet deposition on the balloon injured carotid arteries treated with FG/FGF-1/heparin when compared with balloon injured carotid arteries alone. At 30 days there was an insignificant trend toward decreased thrombogenicity in the FG/FGF-1/heparin treated injured carotids. CONCLUSION: Surface coating with FG/FGF-1/heparin significantly decreases platelet deposition on balloon injured canine carotid arteries after 2 hours of perfusion and may be clinically applicable in endarterectomy and angioplasty procedures. The long-term induction of reendothelialization of arterial surfaces by this technique is under investigation.

Animals↗

PubMed1997

Fibrin glue containing fibroblast growth factor type 1 and heparin with autologous endothelial cells reduces intimal hyperplasia in a canine carotid artery balloon injury model.

PURPOSE: Intimal hyperplasia plagues all types of vascular intervention. Early confluent re-endothelialization may attenuate the smooth muscle cell (SMC) proliferative response. We previously reported that fibroblast growth factor type 1 (FGF-1) and heparin at relative concentrations of 10 ng/ml:250 U/ml delivered in a fibrin glue (FG) suspension can selectively stimulate endothelial cells (EC) and inhibit SMC proliferation in cell culture. This current study evaluates this surface treatment with and without seeded autologous ECs on intimal hyperplasia in a canine carotid artery balloon injury model. METHODS: Twenty-nine adult dogs underwent bilateral balloon injury to a 6 cm segment of their carotid arteries. The injury resulted in a reproducible removal of the intima and 4 to 6 medial lamellae. Nine dogs were used in part I to determine the percent retention of FGF-1 and EC when applied in a FG suspension to the balloon-injured carotid arteries. Part 2 used the remaining 20 dogs to determine the effect of this surface treatment on intimal hyperplasia. In 10 group I dogs, FG (fibrinogen 32.1 mg/ml and thrombin 0.32 U/ml) containing FGF-1 (11 ng/ml) and heparin (250 U/ml) was applied to the luminal surface of one carotid artery, whereas the contralateral carotid artery underwent balloon injury alone. In 10 group II dogs, an identical FG preparation with FGF-1 and heparin was applied to the surface of one carotid artery, whereas the contralateral carotid artery received FG/FGF-1/heparin that also contained autologous ECs (P3; 5 x 10(4) to 10 x 10(4) cells/cm2). Five dogs from both group I and group II were killed at 10 days and the remaining 10 dogs at 30 days. Histologic analysis and computerized morphometric analysis were used to determine intimal and medial thickness and area, percent endothelialization, and medial SMC proliferative rate. RESULTS: There was no measurable neointima in any 10-day dog. There was no difference in neointimal area between the treatments in group I 30-day dogs. There was a significant decrease in maximal neointimal area, intima/media thickness ratio, and intima/media area ratio in group II 30-day dogs that were treated with FG/FGF-1/heparin plus EC. There was an insignificant increase in percent EC coverage and an insignificant decrease in medial SMC proliferative rate in group II 10-day dogs treated with FG/FGF-1/heparin plus EC. CONCLUSIONS: In this canine carotid model, FG with FGF-1 and heparin did not induce significant intimal or medial thickening after 10 or 30 days when compared with vessels that were only balloon-injured. The seeding of autologous ECs within the FG/FGF-1/heparin suspension caused a reduction in neointima formation with no concomitant medial thickening 30 days after injury. The use of FG to locally deliver FGF-1 and ECs may have clinical relevance in the inhibition of intimal hyperplasia.

Animals↗

PubMed1997

Carotid endarterectomy for recurrent stenosis.

PURPOSE: The purpose of this study was to report our results in the surgical management of recurrent carotid stenosis (RCS) after carotid endarterectomy (CEA). METHODS: In a 20-year period, we performed 1209 CEAs; 82 operations (6.8%) were for RCS. There were 33 men and 36 women, with an average age of 66.3 years. Nine patients underwent two redo CEAs and two patients underwent three redo CEAs for either bilateral recurrence or a second recurrence on the same side. Overall, 10 patients were identified with a second recurrence. RESULTS: The average time to presentation with RCS was 65 months (range, 3 to 361 months). The majority of patients (66%) were symptomatic, 34% had transient ischemic attacks, 17% had amaurosis fugax, 9% had strokes, and 6% had nonhemispheric symptoms. Before repair, angiograms were obtained. Patch repair was performed in 61 procedures (74%), 41 with vein, 11 with Dacron, and nine with polytetrafluoroethylene. Autogenous or synthetic bypass grafts were used in 20 procedures (24%), vein in eight, Dacron in two, and polytetrafluoroethylene in 10. In one patient, an occluded internal carotid artery was ligated and an endarterectomy of the external carotid artery was performed without a patch. The operative stroke rate was 4.8%. Minor complications included transient or permanent cranial nerve deficits in 7.3% and wound hematomas in 2.4%. CONCLUSION: Although repeat endarterectomy to treat RCS is technically more demanding, it can be performed safely. Long-term follow-up examination shows that a second recurrence may develop, and we recommend serial noninvasive testing.

Aged↗

PubMed1997

Effects of albumin coating of knitted Dacron grafts on transinterstitial blood loss and tissue ingrowth and incorporation.

Transinterstitial blood loss at implantation and the degree of graft incorporation and inner capsule thickening was compared in serial explants of albumin-coated Dacron versus blood preclotted Dacron grafts in the canine thoracoabdominal aortic position (8 mm internal diameter x 30 cm length). The coated grafts were Bard DeBakey Vasculour II knitted Dacron prostheses impregnated with carbodiimide-cross-linked human albumin. Control grafts were otherwise identical and preclotted with the recipients' whole blood before heparinization during surgery. Transinterstitial blood loss after establishing flow was measured by weighing sponges wrapped around the grafts. Albumin pretreatment resulted in significantly less median blood loss (5.1 g versus 11 g, P=0.04; Mann-Whitney rank sum test). Grafts were explanted at 1 week, 4 weeks, 10 weeks, and 20 weeks. Patency was 100% in both groups. Graft incorporation at explantation was graded by the surgeon as: 1 = none, 2 = minimal, 3 = moderate, or 4 = extensive. No significant differences were noted at any time period. Inner capsule thickness measurements were made every 2.5 mm along the length of all explants. Grafts explanted at 1 week displayed no inner capsules. By 20 weeks, median inner capsule thickness was significantly less in albumin-coated grafts (190 microm versus 235 microm; P<0.0001). These inner capsules in both groups formed as islands, containing abundant myofibroblasts and collagen, covered by endothelial cells and surrounded by residual fibrin coagula. In conclusion, albumin-coated knitted Dacron grafts displayed less transinterstitial blood loss at implantation, and qualitatively similar incorporation, but significantly thinner inner capsules at 20 weeks.

Animals↗

PubMed1996

ePTFE coating with fibrin glue, FGF-1, and heparin: effect on retention of seeded endothelial cells.

In an attempt to improve the resistance of seeded endothelial cell (EC) to desquamation due to shear stress, we evaluated the effect of coating expanded polytetrafluoroethylene (ePTFE) grafts with fibrin glue (FG) containing fibroblast growth factor 1 (FGF1) and heparin on the retention of EC exposed to pulsatile flow ex vivo. Five pairs of ePTFE grafts (30 microm internodal distance, 4 mm internal diameter, 7 cm long) were coated with either FG/FGF-1/heparin (fibrinogen 32.1 mg/ml, thrombin 0.32 U/ml, FGF-1 11 ng/ml, heparin 250 U/ml) or fibronectin (FN) (20 microgram/ml). Canine jugular vein endothelial cells (Factor VIII, passages 5-7), were radiolabeled with indium-111 (100 microCi/1 million cells). Cell seeding (3 x 10(5) cells/cm2) was achieved by four successive inoculations of cells separated by 90 degree graft rotations. After overnight incubation (37 degrees C), pairs of FG and FN grafts (5 cm long) were simultaneously perfused ex vivo with culture media containing 10% fetal bovine serum (120/80 mm Hg, 90 cc/min, 60 pulsations/min). During the 1-hr perfusion, perfusate samples were taken at 0, 5, 15, 30, and 60 min to determine radioactivity loss. Pre- and postperfusion whole graft radioactivity data were compared to estimate cell retention and confirmed by histologic evaluation. Mean adherent radioactivity on FG-coated grafts (96 +/- 5%) was significantly higher (P = 0.0029, Student's t test) than on FN-coated grafts (85 +/- 3%). Maximum radioactivity loss in perfusate was seen after 5 min, with lower sustained loss thereafter. The improved retention of seeded EC on ePTFE grafts coated with FG containing FGF-1 and heparin compared to FN will need to be confirmed for longer durations of perfusion and using in vivo models.

Animals↗

PubMed1996

Biointeractive polymers and tissue engineered blood vessels.

The regulation of endothelial cell (EC) and smooth muscle cell (SMC) proliferation following vascular interventions is critical to clinical efficacy. Our laboratory has developed a method of impregnating biomaterials with suspensions containing bioactive proteins resulting in the capability of differentially modulating EC and SMC growth in vitro and in vivo following implantation. We have previously reported that 60 mu internodal distance ePTFE grafts impregnated with fibrin glue (FG) containing FGF-1 and heparin develop confluent endothelialization with transiently increased EC and SMC proliferation after 4 weeks in dogs. Thoraco-abdominal implants after 20 weeks were developed significantly thicker (139 mu) inner capsules in response to the FGF. To minimize SMC proliferation we studied the effects of FGF-1, heparin, and thrombin concentrations on SMC growth in vitro. FG caused a 182% increase (P < 0.001) in DNA synthesis. Heparin within FG diminished this effect in a dose-dependant manner, with complete inhibition of FG-induced growth at 500 U ml-1 (versus FG alone, P < 0.001). FGF-1 within FG without heparin had no effect, but together, FGF-1 caused a dose-dependant growth increase while increasing heparin concentrations initially increased and then decreased proliferation. FGF-1 and heparin in the medium of quiescent SMCs had similar effects. Only thrombin concentrations > 3.2 U ml-1 stimulated SMC growth and this stimulation was blocked by heparin. A synergism between FGF and heparin on EC proliferation was also found but without EC growth inhibition in response to higher concentrations of heparin. It is thus possible to modulate the relative proliferative activity of ECs versus SMCs by altering the FGF:heparin ratio. This same system may be useful with other proteins to induce other local affects by the applied protein or systemic affects following release of that protein.

Animals↗

PubMed1996

Dacron stimulation of macrophage transforming growth factor-beta release.

This study evaluated the effect of Dacron on the release of macrophage transforming growth factor-beta (TGF-beta),an endothelial cell growth inhibitor. Rabbit peritoneal macrophages were grown in minimum essential medium (MEM) with 10% fetal bovine serum (FBS) in the presence or absence of Dacron (0.5 mm x 3 mm particles). Media were collected three times each week for 7 weeks. For the TGF-beta bioassay, mink lung epithelial cells (CCL64) were grown in MEM with 10% FBS. Test-conditioned media, 100 mu 1, were added (n = 4), and incubated 48 h. 3(H)-Thymidine (3(H)-TdR) uptake was determined and compared with 3(H)-TdR uptake using known pure TGF-beta standards. Media samples were additionally pre-incubated with a neutralizing anti-TGF-beta(1) antibody and the 3(H)-TdR uptake again quantitated. TGF-beta activity in the conditioned media of macrophages exposed to Dacron exceeded the control media groups in all weeks, reaching significance (P<0.05) in weeks 3, 4,5, 6 and 7. Pre-incubation of media samples with the anti-TGF-beta antibody inhibited this TGF-beta activity in all weeks with statistical significance in weeks 1, 2, 3, 5 and 7. The inhibitory effects of Dacron on endothelialization may be explained by the Dacron-induced release of TGF-beta from macrophages.

Animals↗

PubMed1996

The changing face of carotid endarterectomy.

PURPOSE: The economic milieu and improvements in care have altered the diagnostic and therapeutic algorithm of the patient with carotid stenosis. This study analyzes the efficacy and safety of these changes. METHODS: The records of patients who underwent 320 consecutive carotid endarterectomies performed by three surgeons at our institution from 1990 to 1994 were reviewed retrospectively. Use of diagnostic angiography, use of carotid duplex ultrasound, length of hospital stay, postanesthesia recovery observation, intensive care unit (ICU) observation, complications, and hospital charges were analyzed. RESULTS: The average length of hospital stay decreased from 6.18 days to 2.00 days (p < or = 0.001). The day of discharge decreased from 3.10 days to 1.24 days after surgery (p < or = 0.01). By 1993, 68% were discharged by the first day after surgery, increasing to 73% by 1994. From 1990 to 1992, average postoperative ICU observation time fluctuated between 18 and 25 hours; this time decreased to 12.2 hours by 1994. In 1993, only 12.5% of patients were admitted to the ICU, down from 94.8% in 1990; by 1994, only 7.3% were admitted to the ICU (p < or = 0.001). Postanesthesia recovery observation time decreased from 3.77 hours to 1.63 hours during this time (p < or = 0.04). With regard to preoperative diagnosis, angiography was performed in 93.1% of patients in 1990; by 1994, only 32.8% underwent this procedure (p < or = 0.0001). Average hospital charges decreased significantly (1990, $14,378; 1994, $10,436) with these modifications in patient care (p < or = 0.001). The complication rate reflected no significant changes over the course of the study. There were six incidences of cerebrovascular accident (6/320, 1.9%), including one death. There were four incidences of transient ischemic attack (4/320, 1.3%), with no significant differences noted from year to year. CONCLUSIONS: This study confirms the changing nature of carotid endarterectomy and documents that these changes have not adversely affected the safety of the operation.

Adult↗

PubMed1996

Intensive care after carotid endarterectomy: a prospective evaluation.

BACKGROUND: Through prior investigation we established that only a small minority of patients who undergo carotid endarterectomy (CEA) have a complicated postoperative course requiring an intensive care unit (ICU) stay. An appropriate policy for patient management was established. This study prospectively analyzes the safety and efficacy of this policy. STUDY DESIGN: Patients were transferred directly to a nonmonitored surgical ward, regardless of preoperative comorbidity, if they remained stable from a neurologic and a hemodynamic standpoint during a short (less than three hour) stay in the recovery room. Patients whose status was questionable remained in recovery longer or were transferred to an ICU. RESULTS: One hundred forty-six (79 percent) of 185 patients were transferred safely to a ward. Average length of stay in recovery was one hour 59 minutes. No complications occurred that required a return to the operating suite or a move to an ICU. Most of these patients (88 percent) were discharged within 24 hours of surgery. Thirty-nine (21 percent) patients, each identified in recovery, required intervention or monitoring in an intensive care setting. Fourteen required prolonged, aggressive intravenous treatment of hypertension; 14 had sustained hypotension; three were observed to rule out myocardial infarction, and three had neurologic deficits. Two patients had ventricular arrhythmias, two had wound hematomas, and one patient required reintubation. This group (n = 39) remained in the recovery room two hours 40 minutes on average, spent 20 hours in the ICU, and remained in the hospital 32 hours after CEA. CONCLUSIONS: Most patients who undergo CEA follow a predictably benign postoperative course. Patients are easily identified by a recovery room protocol and approximately 80 percent can avoid ICU costs.

Aged↗

PubMed1995

In vivo platelet deposition on polytetrafluoroethylene coated with fibrin glue containing fibroblast growth factor 1 and heparin in a canine model.

BACKGROUND: We previously reported that the coating of expanded polytetrafluoroethylene (ePTFE) with fibrin glue containing fibroblast growth factor 1 (FGF-1) and heparin accelerates endothelial coverage of grafts implanted into animals. We report here the effect of this surface modification on early platelet deposition. MATERIALS AND METHODS: Nine dogs received 7-cm ePTFE grafts, 60-microns internodal distance, 4-mm internal diameter, as bilateral aortoiliac implants, one coated (luminal cross section and abluminal surface) with fibrin glue (fibrinogen 32.1 mg/mliters, thrombin 0.32 U/mliters) containing FGF-1 (11 ng/mliters and heparin (250 U/mliters), the other uncoated. After 5, 30, or 120 minutes of circulation with blood containing autologous platelets radiolabelled with indium 111, gamma emissions were quantitated on explants and correlated to surface areas measured by computerized planimetry. RESULTS: Both global and segmental comparisons showed significantly (P < 0.05, Student's t-test) less platelet deposition on coated than on uncoated grafts after 120 minutes of circulation, but no difference at 5 and 30 minutes. CONCLUSIONS: In this model, ePTFE coating with fibrin glue containing FGF-1 and heparin shows no adverse effect on early platelet deposition.

Animals↗

PubMed1995

Selective stimulation of endothelial cell proliferation with inhibition of smooth muscle cell proliferation by fibroblast growth factor-1 plus heparin delivered from fibrin glue suspensions.

BACKGROUND: Pretreatment of expanded polytetrafluoroethylene grafts with fibrin glue (FG) containing fibroblast growth factor-1 (FGF-1) (10 ng/ml) and heparin (50 units/ml) has been shown to induce a transmural angiogenesis with proliferation of both endothelial cells (ECs) and smooth muscle cells (SMCs) in dogs. To induce EC without SMC proliferation, we studied the effects of different FGF-1:heparin ratios within FG in vitro. METHODS: First passage human umbilical vein ECs (factor VIII+) or primary canine carotid artery SMCs (alpha-actin +) were seeded onto 96-well plates coated with FG containing 10 ng/ml FGF-1 and 0, 5, 50, or 500 units/ml heparin. Control wells were coated with FG without FGF-1 or heparin. Cells were fed standard growth medium without soluble FGF-1 or heparin. Tritiated thymidine (1 microCi/well) was added after 1, 2, or 3 days, and proliferation was assayed by scintillation counting 48 hours later. RESULTS: For both ECs and SMCs, proliferation on FG containing FGF-1 but no heparin was not different from control. EC proliferation on FG containing FGF-1 was significantly increased by addition of 5, 50, or 500 units/ml heparin (+68%, +99%, and +106%, respectively; p (0.0001 for all), reflecting the synergism of FGF-1 by heparin. SMC proliferation was also significantly increased by the addition of 5 or 50 units/ml heparin (+85% and +66%, respectively; p (0.0001 for both). However, SMC proliferation with 500 units/ml heparin was significantly decreased from control (-12%; p = 0.014), reflecting heparin's SMC growth inhibitory activity. CONCLUSIONS: FG containing 10 ng/ml FGF-1 and 500 units/ml heparin stimulates EC proliferation while inhibiting SMC proliferation in vitro. Application of this modified FG to vascular grafts or to arteries after direct or transcutaneous interventions may promote endothelialization without intimal hyperplasia.

Cell Division↗

PubMed1994

FGF-1 affixation stimulates ePTFE endothelialization without intimal hyperplasia.

The affixation of FGF-1 to porous vascular grafts has been reported to stimulate capillary ingrowth and surface endothelialization. The current study further characterizes responses to fibroblast growth factor (FGF)-1 affixation to 30-cm-long grafts followed 140 days. ePTFE grafts (30 cm x 8 mm i.d.), 60 microns internodal distance, were impregnated with fibrin glue (FG) suspensions containing FGF-1 and heparin. Two negative control groups were treated either with FG with heparin alone or left untreated. Grafts were explanted from the canine thoracoabdominal aortic position after 10, 30, or 140 days (n = 3/time/group) 10 hr after im injection of tritiated thymidine (0.5 muCi/kg). Specimens were studied by light and electron microscopy, immunohistochemistry, morphometric analyses, and cross-sectional autoradiography. RNA preparations from inner capsule tissues were used for reverse transcription-polymerase chain reaction (RT-PCR) analyses of FGF-1, FGF-2, transforming growth factor-beta 1, (TGF-beta 1) and FGF receptor mRNA species. Inner capsule collagen was quantitated by hydroxyproline colorimetry. Histologic analyses of perianastomotic regions were performed for comparison purposes. All explants were patent and without intimal hyperplasia. Progressive capillarization of the internodal spaces occurred over time and was significantly more extensive in the FGF-1-treated group. Endothelialization of the luminal surface increased with time, at 140 days covering 86.7 +/- 11.6% of the FGF-1 explants vs 46.1 +/- 7.5% and 48.1 +/- 13.3% in the other groups, P < 0.007 and P < 0.04, respectively. Inner capsule thickness at 140 days differed significantly (P < 0.05) between the FGF-1 group (138.8 microns) vs either control group (93 and 67 microns, respectively), which did not significantly differ from each other. Cross-sectional autoradiography demonstrated an FGF-1-induced mitotic index increase at 30 days, 9.6 +/- 4.4% compared to 2.5 +/- 1.0 and 0 +/- 0%, respectively, with both myofibroblasts and endothelial cells incorporating the [3H]thymidine label. The mitotic index returned to quiescent levels at 140 days (< 1% in all groups). Collagen content increased with time in all groups, significantly greater in both FG groups vs untreated controls at 30 and 140 days. RT-PCR analyses revealed FGF-1, FGF-2, FGFR-1 (flg), and TGF-beta 1 mRNA in all samples without evidence of modulation by FGF-1 affixation. These data demonstrate FGF-1-induced graft capillarization and surface endothelialization without functionally significant intimal hyperplasia in this model.

Animals↗

PubMed1994

Carotid endarterectomy without arteriography: the preeminent role of the vascular laboratory.

The classic workup of patients considered for carotid endarterectomy (CE) has included contrast arteriography to delineate the nature and extent of the arterial pathology. Noninvasive testing (NIT) consisting of duplex scanning plus sound spectrum analysis is an alternative method for accurately evaluating the carotid bifurcation. The accuracy of our laboratory in comparing NIT to contrast arteriography has been established by use of the guidelines suggested by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Forty-two patients underwent CE based on NIT alone. Seventeen had hemispheric transient ischemic attacks or minor strokes, six had amaurosis fugax, three had nonspecific symptoms, and 16 were asymptomatic. NIT identified a severe stenosis that was limited to the carotid bifurcation; the internal carotid artery distal to the bulb was normal. The predicted stenotic atherosclerotic lesion was confirmed at operation in all patients. One patient had a high bifurcation that required an extension of the original incision. Of three undiagnosed kinked distal internal carotid arteries found at operation, only one required surgical correction. No transient ischemic attacks, strokes, or deaths occurred postoperatively. CE can be performed in selected patients based on NIT alone, obviating the mortality, morbidity, and cost of arteriography. This algorithm demands that the NIT is unequivocal and the accuracy of the testing laboratory is established and maintained according to published standards.

Arteriosclerosis↗

PubMed1994

Intraoperative duplex scanning and late carotid artery stenosis.

PURPOSE: The purpose of this study was to assess the effect of intraoperative duplex scanning on early and late results after carotid endarterectomy. METHODS: We reviewed 316 carotid arteries in 283 patients who underwent operation since 1986. The results of intraoperative ultrasonography were normal in 254 (80.4%) and abnormal in 62 (19.6%). We did not reexplore 53 (85.5%) of the abnormalities because the defect was minor, 2 to 3 mm or less. These defects were retained atheroma in the common carotid artery (n = 35), internal carotid artery (ICA) (n = 5), external carotid artery (n = 2), small frond in the bulb (n = 2), thickened wall of the vein patch (n = 2), and ICA kink (n = 7), two of which were associated with retained atheroma. Nine defects (14.5%) were reexplored and repaired; there were seven flaps, one residual plaque, and one case with turbulent flow alone. RESULTS: Patients with a normal examination result had an early ICA occlusion rate of 0.79% (n = 2), an early stroke rate of 1.6% (n = 4), and one death (0.4%). In the unrepaired group these rates were 1.9% (n = 1) and 1.9% (n = 1), respectively. No occlusion occurred in the repaired group, but one preexisting cerebrovascular accident worsened immediately after operation. Frequency analysis and B-mode imaging were performed after operation and every 6 to 12 months in all patients (mean 21.6 months). A greater than 75% area stenosis was found in nine (17%) of the 53 unrepaired carotid arteries, but in only four (4.3%) of the 254 carotid arteries lacking defects and in one of the reopened group (p < 0.001). There have been no late strokes, and only three late transient ischemic attacks overall. CONCLUSIONS: A normal intraoperative scanning result obtained after carotid endarterectomy is associated with improved late patency rates. Even small defects appear to be associated with an increased incidence of late restenosis, reemphasizing the importance of technical perfection.

Adult↗

PubMed1993

Kinetics of cell proliferation as a function of vascular graft material.

Bioresorbable vascular grafts constructed for polyglactin 910 (PG910) and polydioxanone (PDS) and nonresorbable Dacron were interposed into the infrarenal abdominal aortas of New Zealand White rabbits. The prosthesis/tissue complexes were harvested after 2, 3, 4, 12, and 52 weeks. Seventeen, 9, and 1 h prior to sacrifice, animals received tritiated thymidine (0.5 mCi/kg/dose). All specimens were studied grossly and by light and transmission electron microscopy. Mitotic indices (MI's) were determined by autoradiography for inner capsule myofibroblasts at the proximal, mid, and distal segments of each prosthesis. There were no aortic-related deaths. All grafts were patent with no aneurysmal dilatation. At 4 weeks, PG910 resorption was evidenced by macrophage phagocytosis, less so in PDS while Dacron remained intact. At 12 weeks, the PG910 was completely resorbed while PDS resorption continued. The latter was completely resorbed by 52 weeks. There was no significant difference in MI's between proximal, mid, and distal regions for each graft type. The mitotic index paralleled the rate of prosthetic resorption in both PG910 and PDS groups, as high as 28.34 +/- 23.21 in the former 3 weeks after implantation and significantly higher at 4 weeks (7.58 +/- 2.02 and 7.50 +/- 2.66, respectively) than at 52 weeks (0.72 +/- 0.98 and 1.00 +/- 0.22, respectively) in both groups. The mitotic index in the Dacron group never surpassed 1.22 +/- 0.90. We conclude that higher levels of early cell proliferation in bioresorbable grafts closely parallel the kinetics of prosthetic resorption.

Animals↗

PubMed1993

Basic fibroblast growth factor production in vitro by macrophages exposed to Dacron and polyglactin 910.

Macrophage activation by implanted blood-contacting biomaterials modulates smooth muscle cell and endothelial cell ingrowth. The present study evaluates the in vitro interactions between Dacron or polyglactin 910 with macrophages derived from rabbits fed either normal or atherogenic diets. Peritoneal macrophages were cultured in the presence or absence (negative controls) of either biomaterial for 7 weeks. Conditioned media was evaluated for mitogenic activity using a rabbit aortic smooth muscle cell bioassay with or without preincubation with neutralizing anti-basic-FGF antibody. Results demonstrated increased mitogen release from macrophages harvested from the atherosclerotic rabbits. Only macrophages harvested from normal diet fed rabbits increased their mitogen release following exposure to either polyglactin 910 (p < 0.05) or to Dacron (p < 0.005) over controls. The stimulation of mitogen release by polyglactin 910 did not significantly exceed that in response to Dacron. In rabbits fed normal diets neutralization with the anti-basic-FGF antibody inhibited 100% of the Dacron induced mitogen release as compared to 36% of the polyglactin 910 induced mitogen release (p < 0.01). These results demonstrate significant induced mitogen release from macrophages exposed to biomaterials in vitro, much of the smooth muscle cell mitogen represented by basic-FGF.

Animals↗

PubMed1993

An 11-year experience with aortofemoral bypass grafting.

Over the past 11 years, 224 patients (440 limbs) underwent aortofemoral bypass grafting for claudication (63%) or limb-threatening ischemia (37%). The distal anastomosis included the profunda femoris artery directly or only as a profundaplasty in 163 limbs (37.0%). Concomitant distal bypasses were carried out in 19 limbs (4.3%). The perioperative mortality rate was 4.9%; over half of the deaths (six) were from myocardial infarction. There were ten early graft limb occlusions (2.3%). Only five major amputations (1.1%) occurred. Long-term follow-up of 416 limbs averaged 58.5 (range 2-142) months. Cumulative primary and secondary patency rates were 88 and 93% respectively at 5 years, and 73 and 89% respectively at 10 years. The cumulative limb salvage rate was 95% at 5 years and 91% at 10 years. Improvement of claudication or relief from limb-threatening ischemia occurred in 90% of limbs early after treatment. Only 5.9% of limbs were worse after operation. During follow-up, 55 patients (38.5%) died, over half from cardiac causes. Long-term graft-related complications included pseudoaneurysm in 16 limbs (3.8%) and graft limb thrombosis in 33 (7.9%), occurring at a mean of 57.8 and 24.8 months respectively. Graft infection occurred in four patients (1.9%). Excluding operations for graft infection, the operative mortality rate in 72 reoperations on 45 patients was 5.5%. In summary, aortofemoral bypass grafting can be performed safely with excellent long-term patency and limb salvage rates. Improvements in the perioperative mortality rate could best be addressed by improvements in cardiac evaluation and perioperative monitoring. Long-term graft limb complications do occur and, therefore, these patients require lifetime surveillance.

Adult↗