Prostacyclin production from seeded prosthetic vascular grafts.

Endothelial cell seeding has been proposed as a method of improving patency rates in small-calibre prosthetic vascular grafts. In vivo, endothelial cells normally produce prostacyclin (PGI2), a potent antiplatelet agent. The aim of this study was to determine whether seeded grafts show significant PGI2 production after in vivo implantation. Grafts were seeded with either autologous canine venous endothelial cells or autologous microvascular endothelial cells. After 12 weeks, PGI2 production was assessed under basal and stimulated conditions. Seeded grafts were compared with non-seeded controls and the corresponding aorta. The overall patency rate in seeded grafts was 80 per cent compared with 10 per cent in non-seeded grafts (P < 0.01). Grafts seeded with cells from either source produced significantly more PGI2 than unseeded grafts in both basal and stimulated states (P < 0.05). The aorta produced significantly more PGI2 than seeded grafts under both conditions (P < 0.01). Endothelial cell seeding produces a functional graft and leads to an improved patency rate.     

Seeding Dacron arterial prostheses with peritoneal mesothelial cells: a preliminary morphological study

A preliminary laboratory study has been undertaken using dogs, in which porous Dacron arterial prostheses have been seeded with autologous peritoneal mesothelial cells before implantation into the arterial system. These cells were harvested from omentum by collagenase digestion and were introduced into the graft at the time of preclotting. Examination of the grafts by scanning and transmission electron microscopy one month after insertion showed no organized cellular lining in the control graft. In three seeded grafts there was a lining of mesothelial cells which extended over the whole surface of the grafts up to 1 cm from the suture lines. Selected areas of the grafts have been analysed morphometrically. In the seeded grafts there is a cellular layer which on average covers 94 per cent of the luminal surface. These results suggest that mesothelial cells, which both secrete prostacyclin and possess fibrinolytic activity, present a possible alternative to endothelium as a cellular lining for prosthetic grafts.     

Seeding human arterial prostheses with mechanically derived endothelium: The detrimental effect of smoking

Endothelial healing of Dacron arterial prostheses can be hastened in dogs by seeding autogenous venous endothelium onto the prostheses in a single-staged operation. To determine whether this technique enhances the patency of human grafts, we studied the results of 186 operations on 161 patients performed between February 23, 1978, and December 1, 1982. Alternately allocating patients to treatment with seeded and unseeded Dacron knitted prostheses, we performed axillary-femoral and axillary-femoral-femoral bypasses in 11 patients (six seeded and five unseeded) and femoral-femoral bypasses in 28 (13 seeded and 15 unseeded). By a randomized block method of treatment allocation, femoral-popliteal grafts were installed in 147 limbs (112 vein, 18 seeded, and 17 unseeded). Patency was analyzed by the life-table method. Overall, femoral-femoral and femoral-popliteal bypasses demonstrated no difference between the seeded and unseeded grafts. Patency was somewhat better in seeded than unseeded axillary-femoral bypasses. Nevertheless, nonsmokers with seeded femoral-popliteal Dacron grafts enjoyed a significantly better graft patency than those with unseeded grafts (p = 0.035), whereas a substantial deterioration of seeded Dacron grafts was observed in those patients who smoked (p = 0.008 at 6 months). Vein grafts performed better than either seeded or unseeded Dacron prostheses (p = 0.016). Serum beta-thromboglobulin (BTG) levels varied widely and did not differ among any of the treatment groups. We concluded that endothelial seeding improved the patency of human arterial prostheses but that results were worse if the patient was a smoker. BTG was not a useful measure of the platelet activation induced by an arterial prosthesis. (J VASC SURG 1984;1:279-89.)     

Endothelial cell seeding of expanded polytetrafluoroethylene vena cava conduits: effects on luminal production of prostacyclin, platelet adherence, and fibrinogen accumulation

The blood-surface interface of 12 mm ID x 5 cm ePTFE vena cava conduits, unseeded (n = 8) and seeded (n = 8) with enzymatically derived autologous endothelial cells, was studied in a canine model at 4 and 12 weeks after graft implantation. Acetylsalicylic acid (325 mg each day) and Coumadin (prothrombin time 1.4 to 1.7 times the control value) were administered preoperatively and continued 4 weeks postoperatively. Platelets labeled with 111In and 125I-labeled fibrinogen were administered 24 hours before graft removal. Luminal platelet adherence, expressed as 10(6) platelets/cm2 of graft surface, was 8.9 +/- 5.6 vs. 56.4 +/- 8.0 (p less than 0.008) and 4.0 +/- 0.9 vs. 12.4 +/- 2.3 (p less than 0.005) in seeded vs. unseeded grafts at 4 and 12 weeks, respectively. Luminal fibrinogen deposition, expressed in micrograms per square centimeter of graft surface, was 11.8 +/- 2.2 vs. 32.0 +/- 2.0 (p less than 0.06) and 6.1 +/- 2.4 vs. 12.4 +/- 6.3 (p less than 0.005) in seeded vs. unseeded grafts at 4 and 12 weeks, respectively. Cumulative 4- and 12-week luminal production of 6-keto-PGF1 alpha from seeded and unseeded grafts represented 11% and 5%, respectively, of that produced from the native iliac vein. Luminal endothelial cell coverage was 71% +/- 22% vs. 33% +/- 9% and 79% +/- 8% vs. 55% +/- 8% (p less than 0.05) in seeded and unseeded grafts at 4 and 12 weeks, respectively. Although endothelialization was not complete in seeded vena cava grafts, it is clear that seeded prostheses exhibited improved thromboresistance compared with unseeded conduits.     

Cardiac release of prostacyclin and thromboxane A2 during coronary revascularization

Cardiac surgery stimulates the systemic synthesis of prostacyclin and thromboxane A2, but the cardiac release of these prostanoids has been reported infrequently. Fifty-four patients undergoing elective coronary artery bypass had coronary sinus catheters inserted to evaluate the cardiac release of the stable metabolites of prostacyclin (6-keto-prostaglandin F1 alpha) and thromboxane A2 (thromboxane B2). Arterial concentrations of 6-keto-prostaglandin F1 alpha and thromboxane B2 were elevated after cardiac cannulation and during cardiopulmonary bypass. The cardiac release of 6-keto-prostaglandin F1 alpha was observed after cannulation and during, but not after, cardiopulmonary bypass. Cardiac thromboxane B2 release was detected after cross-clamp release and persisted during the early postoperative period when cardiac 6-keto-prostaglandin F1 alpha release was no longer detectable. Cardiopulmonary bypass stimulated the systemic production of thromboxane and prostacyclin. The cardiac release of thromboxane was unopposed by cardiac prostacyclin production in the early postoperative period and may contribute to reperfusion injury.     

Complement activation by synthetic vascular prostheses

Morphologic evaluation of synthetic grafts (both seeded and unseeded) harvested within 2 weeks of implantation has revealed heavy infiltration with polymorphonuclear leukocytes (PMNs). Since complement-activated PMNs are known to damage endothelial cells, we hypothesized that complement activation might prove a barrier to optimal endothelial cell seeding of prosthetic grafts. To determine whether synthetic vascular prostheses activate complement and whether the type of graft material influences the degree of activation, we assayed the plasma of 10 healthy donors for complement activity following incubation with short segments of knitted Dacron and polytetrafluoroethylene (PTFE) graft material. C5a generation was measured by radioimmunoassay and granulocyte aggregometry. Standard hemolytic assays were used to determine depletion of functional classical pathway (CH50 and C4) alternative pathway (APH50) activity. Results indicated substantial complement activation by Dacron and virtually none by PTFE. Activation by Dacron appeared to occur via both complement pathways. Such complement "reactivity" may have important implications for the performance of prosthetic materials as small-caliber vascular grafts, whether seeded with endothelial cells or not.     

Aprotinin decreases release of 6-keto-prostaglandin F1 alpha and increases release of thromboxane B2 in cultured human umbilical vein endothelial cells.

Use of the proteinase inhibitor aprotinin significantly improves hemostasis and reduces bleeding after operations in which extracorporeal circulation is used. The mechanism of action, however, has been only partially clarified. In this work we investigated whether aprotinin influenced the production and release of the eicosanoids prostacyclin, measured as the stable metabolite 6-keto-prostaglandin F1 alpha, and thromboxane A2, measured as the stable metabolite thromboxane B2, from endothelial cells. Human umbilical vein endothelial cells were incubated with different concentrations of aprotinin (5.5, 20, 55, and 100 mumol/L). The levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 were measured at baseline and after thrombin stimulation. A concentration-dependent effect of aprotinin on 6-keto-prostaglandin F1 alpha synthesis was demonstrated. After incubation with 100 mumol/L of aprotinin, a 90% reduction in 6-keto-prostaglandin F1 alpha production was seen (31.69 versus 307.44 picograms per million cells; p less than 0.001). Conversely, thromboxane B2 production showed a 345% increase after incubation with aprotinin (287.80 versus 83.82 picograms per million cells; p less than 0.0001). Since 6-keto-prostaglandin F1 alpha inhibits and thromboxane B2 strongly enhances platelet aggregation, it appears that one mechanism of the clinically observed effectiveness of aprotinin lies in the altered ratio of 6-keto-prostaglandin F1 alpha: thromboxane B2 in endothelial cells, which leads to enhanced platelet aggregation and improved vessel sealing.     

Host response to autologous endothelial seeding

Dacron and expanded polytetrafluoroethylene grafts, seeded with autologous venous endothelial cells at the time of implantation, subsequently develop endothelial linings. However, it has not been shown whether the endothelial cells in these linings are derived from the seeded cells, or whether the seeding process itself stimulates host endothelial cells to proliferate and cover the grafts. As a first step in testing this hypothesis, bilateral end-to-side aortoiliac expanded polytetrafluoroethylene grafts with an internal diameter of 6 mm, an internodal distance of 22 microns, and an average length of 9.2 cm were placed in 10 adult mongrel dogs weighing 20 to 25 kg; the aorta was ligated just distal to the origin of the grafts. The graft on one side, chosen at random, was seeded with autologous endothelium that was harvested by enzyme single-stage technique from external jugular veins; the other side was not seeded. After 4 weeks the animals were anesthetized and heparinized, and the grafts were fixed by perfusion in vivo with 2.5% glutaraldehyde solution before they were removed. Both grafts occluded in two animals, and both grafts were patent in five animals. In two animals the seeded grafts were open and the unseeded grafts were occluded. In one the seeded graft was occluded and the unseeded graft was patent. There was no significant difference in clot-free surface area between seeded (29% +/- 18%) and unseeded (31% +/- 11%) grafts. Scanning electron microscopy showed the presence of an endothelial monolayer that averaged 39% +/- 20% and 36% +/- 26% coverage, respectively, in the clot-free midgraft portions of all seeded and unseeded patent grafts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Seeding arterial prostheses with vascular endothelium. The nature of the lining.

Arterial prostheses seeded with autogenous vascular endothelium demonstrate a well-organized, cellular, inner lining. To determine the nature of the lining cells, six animals underwent replacement of the infrarenal aorta with Dacron prostheses. During the preparation of three such grafts, endothelium was scraped from the saphenous vein with a steel wool pledget, suspended in chilled Sack's solution, and mixed with blood used to preclot the graft. This suspension was omitted from the three control grafts. After six weeks, the grafts were removed, rinsed and examined. Fluorescent Factor VIII related antigen (F VIII-RA) strongly stained the lining cells. Silver nitrate Haütchen and electron microscopy preparations revealed a lining pattern characteristic of vascular endothelium. Endothelial cell-specific Weibel-Palade bodies were identified in the lining cell cytoplasm. Masson's trichrome staining revealed a relatively collagen-poor connective tissue within the seeded fabric. Transmission electron microscopy disclosed vascular smooth muscle cells between the seeded graft fabric and the lining cells. Vasa vasorum, arising from the outer capsule, penetrated the fabric to supply the inner capsules of the seeded grafts. It is concluded that the cells lining seeded canine arterial prostheses are true vascular endothelium supported by vascular smooth muscle cells, that the lining contains minimal connective tissue, and that vasa vasorum develop. Unseeded control grafts lacked these features.     

Platelet aggregability after endoscopic intravariceal injection of 5 per cent ethanolamine oleate into oesophageal varices

Platelet aggregability and the coagulative and fibrinolytic systems were examined in 45 patients who underwent endoscopic injection sclerotherapy for oesophageal varices. Five per cent ethanolamine oleate, the sclerosant used, was injected into the oesophageal varices. There were significant increases in the concentrations of fibrinopeptide A, fibrinopeptide B-beta-15-42 and fibrin degradation products-E after the sclero-therapy. At 1 h after the sclerotherapy the mean(s.e.m.) platelet aggregation was significantly suppressed to 71.9(4.2) per cent of that before the treatment (P less than 0.01). There was a gradual recovery within 1 week to the same level seen before the sclerotherapy. Thromboxane B2 and 6-keto-prostaglandin F1 alpha, both stable products of thromboxane A2 and prostacyclin respectively, showed significant temporary increases after the sclerotherapy (P less than 0.01). The peak increase in the level of thromboxane B2 was noted within 1 h after the sclerotherapy and earlier than that for 6-keto-prostaglandin F1 alpha. This increased ratio of prostacyclin and thromboxane A2 may be related to the marked limitation in platelet aggregation.     

Prostaglandin biochemistry of seeded endothelial cells on Dacron prostheses

The beneficial effect of seeding endothelial cells on synthetic vascular conduits has been well established. The biochemical production and interaction of the prostaglandins, prostacyclin (PGI2) and thromboxane (TxA2), were studied on Dacron vascular grafts that were seeded with autogenous venous endothelial cells. Seventy-three seeded and nonseeded grafts were implanted into the carotid arteries of dogs. Animals were medicated with either cyclooxygenase inhibitors (aspirin and dipyridamole, or ibuprofen, or U-53,059), or dipyridamole alone, or a thromboxane synthase inhibitor, U-63557A. All animals were killed at 5 weeks and analyzed for patency, thrombus-free surface (TFS), and PGI2 and TxA2 production from mid-graft punch biopsies. PGI2 and TxA2 identifications were made by radioimmunoassay determination of 6-keto PGF1 alpha and TxB2, respectively. Results of the study demonstrated in nonmedicated animals a slightly increased patency rate in seeded vs. nonseeded grafts (50% vs. 40%) and a more significant difference in TFS (49% vs. 24%). The addition of cyclooxygenase inhibitors or TxA2 synthase inhibitors significantly improved both patency (90% vs. 47%) and TFS (87% vs. 9%) in seeded vs. nonseeded grafts. PGI2 production was decreased in seeded grafts with the use of cyclooxygenase inhibitors in all cases. It is concluded that seeded endothelial cells on Dacron velour grafts can synthesize PGI2; these PGI2 levels are far less than PGI2 levels produced by endothelial cells from the adjacent carotid artery; and TxA2 synthase inhibitors best improve thromboresistance of seeded grafts without significant reduction in PGI2 production.     

Seeding of ePTFE carotid interposition grafts in sheep and dogs: species-dependent results

Autologous endothelial seeding of thin-walled ePTFE vascular prostheses (I.D.4 mm), interposed in the carotid artery, was performed in 10 dogs and 14 sheeps. Aspirin (250 mg/day) and dipyridamole (75 mg/twice daily) were given throughout the study as antiplatelet therapy. Animals were killed 2 and 5 weeks after surgery. Patency rates for seeded grafts in dogs were 75% (6:8) and 83% (10:12) at 2 and 5 weeks, respectively. In control grafts the patency rates were identical. Patency rates for seeded grafts in sheep were 0% (0:5) and 11% (1:9) at 2 and 5 weeks, respectively. Control grafts in sheep had a patency rate of 40% (2:5) and 0% (0:9) at corresponding times. Scanning electron microscopy showed an almost complete endothelialization of seeded grafts in dogs after 5 weeks. Platelet deposition was studied in the dogs by means of chromium-51-labeled autologous platelets. Significantly fewer platelets accumulated on seeded grafts, and the ratio of 6-keto-PCF1 alpha to thromboxane B2 was significantly higher, compared with unseeded grafts, which indicated the presence of a functionally active endothelial lining in seeded grafts. Differences in the hemostatic system could account for the high clotting incidence in sheep, compared with that in dogs. Such species differences make extrapolations to the clinical situation from autologous endothelial seeding in experimental animals hazardous.     

Aspirin therapy in small-caliber arterial prostheses: Long-term experimental observations

To study the therapeutic effects of 3 mg/kg aspirin given at the time of surgery and postoperatively, Dacron carotid grafts with an internal diameter of 4 mm and a length of 6 cm were implanted bilaterally in mongrel dogs. Sixteen control grafts in eight subjects and 20 grafts in 10 subjects treated with aspirin were followed by serial angiograms until consecutive studies showed stable patency rates in both groups. Platelet aggregations, malondialdehyde production, serum salicylate levels, and thromboxane A₂ and prostacyclin secretion (measured as thromboxane B₂ and 6-keto-prostaglandin F_1α) were monitored prior to and throughout the experiment. Surface mapping, indium-111 uptake, factor VIII—related antigen staining, and scanning and transmission electron microscopy were performed on the grafts at sacrifice. This study demonstrates a protective effect on the early patency of small-caliber prostheses in the canine model with daily oral aspirin administration. The degree and duration of this effect depends on the preoperative baseline ratio of thromboxane to prostacyclin in each subject. (J VASC SURG 1984;1:839-851.)     

Effects of antiplatelet agents in combination with endothelial cell seeding on small-diameter Dacron vascular graft performance in the canine carotid artery model

The purpose of this study was to assess the success of endothelial cell-seeded and non-seeded small-diameter vascular grafts in dogs medicated with antiplatelet agents. Eighty dogs underwent bilateral carotid artery replacements with 6 cm lengths of 4 mm I.D. double-velour Dacron grafts. In each dog one graft was seeded with enzymatically derived autologous endothelial cells; the contralateral graft was nonseeded. The following anti-platelet medications were administered beginning 4 days preoperatively: aspirin (5 grains every day); dipyridamole (50 mg twice a day); aspirin plus dipyridamole (5 grains each day plus 50 mg twice a day); aspirin (1.25 grains every other day); ibuprofen (10 mg/kg/day); U-53,059, a cyclooxygenase inhibitor (3 mg/kg/day); and U-63557A, a thromboxane synthase inhibitor (10 mg/kg/day). Grafts were harvested 5 weeks postoperatively. Graft success was evaluated by patency, thrombus-free surface area, area endothelialized, and graft production of prostacyclin. None of the medications prevented neoendothelialization of seeded grafts. Mean patencies of endothelial cell-seeded grafts from medicated dogs were significantly greater than mean patencies of endothelial cell-seeded grafts from nonmedicated dogs. The cyclooxygenase inhibitors best maintained patency in nonseeded grafts. Thrombus-free surface areas of endothelial cell-seeded grafts from medicated dogs were significantly greater than from nonseeded control grafts from the medicated dogs. All medications impaired prostacyclin synthesis. We conclude that the combination of endothelial cell seeding plus antiplatelet medication is most efficacious in small-vessel grafting success and that high levels of prostacyclin production by vascular grafts are not necessary to maintain patency in dogs medicated with antiplatelet agents.     

Patency in canine inferior vena cava grafting: effects of graft material, size, and endothelial seeding

We studied 117 inferior vena cava (IVC) replacements in dogs to determine the effects of graft material, graft size, endothelial seeding, and cultured endothelial linings on graft patency. As a control, the IVC was removed and reimplanted in 11 dogs. Dacron (n = 7) and expanded polytetrafluoroethylene (e-PTFE) grafts (n = 12) were seeded immediately with the use of enzymatically derived autogenous jugular vein endothelium. Cultured linings were prepared for e-PTFE grafts (n = 9) by inoculating the graft with jugular endothelium and nurturing the lining in tissue culture for 14 to 30 days before implantation. Unseeded grafts (n = 27) were prepared according to the manufacturer's recommendations. These six methods of preparation were tested in grafts measuring 6 mm I.D. and 60 mm in length. Other sizes were tested with a Latin square study design. After 30 to 60 days the grafts were perfusion fixed and studied with light and transmission electron microscopy. Patency was determined by contrast cavography after 7 and 30 days. Patency in the IVC reimplantation was 100% compared with 28.0% of the e-PTFE (p = 0.001) and none of the Dacron grafts that measured 6 mm I.D. and 60 mm long. e-PTFE and Dacron graft patency also differed significantly (p = 0.035). Seeded and culture-lined e-PTFE grafts in that same size were patent in 31.6% compared with 16.7% of unseeded e-PTFE. With grafts measuring 80 mm long, three of the five e-PTFE grafts were patent between 3 and 7 days. All progressed to occlusion by 30 days and compared poorly with all other graft sizes tested (2.6% progression to occlusion [p = 3 X 10(-8)]). Recanalization was not seen in 10 occluded grafts that were followed for 60 days. The histologic features of seeded grafts differed remarkably from grafts previously studied in the arterial circulation and from culture-lined and unseeded venous prostheses in that 60% had prominent large, random, endothelium-lined channels within the inner capsule. Larger graft diameters (p = 0.009) and the omission of an endothelial surface treatment (p = 0.004) were associated with anastomotic subendothelial fibrous hyperplasia. We conclude that graft material is the major determinant of patency in IVC replacements, that an extensive endothelial surface promotes patency, but that simply seeding e-PTFE or Dacron grafts with 10(5) endothelial cells does not provide sufficient endothelium to alter early patency.(ABSTRACT TRUNCATED AT 400 WORDS)     

Arterial regeneration over polydioxanone prostheses in the rabbit

We analyzed histologic, ultrastructural, and functional characteristics of rabbit aortic conduits regenerated over absorbable polydioxanone prostheses. Twenty-eight polydioxanone-elicited prosthesis/tissue complexes harvested two weeks to 12 months following implantation were analyzed grossly; photographed; sectioned for light, scanning, and transmission electron microscopy; and studied for compliance, bursting strength, and prostacyclin and thromboxane metabolite contents. No aortic-related deaths or hemorrhages occurred. Smooth regenerated conduits without stenoses were seen in 27 of 28 specimens, with one small aneurysm. Transprosthetic myofibroblast migration and proliferation paralleled the kinetics of macrophage-mediated prosthetic dissolution, which was consequently delayed compared with polyglycolic acid prostheses. Confluent endothelial-like luminal surfaces were present after two weeks. Progressive inner capsular thickening ended after three months at 420 micron. Ex vivo compliance curves resembled arterial elasticity. Regenerated tissue withstood 1200 mm Hg of systolic pressure, and 6-keto-prostaglandin F1 alpha to thromboxane B2 ratios did not differ from normal control specimens.     

Anastomotic tensile strength following in situ replacement of an infected abdominal aortic graft

The tensile strength and histologic features of anastomotic bonding were studied prior to and following in situ replacement of aortic vascular prostheses infected by Staphylococcus epidermidis. Sterile (n = 6) and infected (n = 19) Dacron grafts were used to replace the abdominal aorta of 25 dogs. After five weeks, grafts were explanted, and peak tensile force (measured in kilograms) required for anastomotic disruption was measured using a linear gain tensiometer. Anastomotic tensile strength (mean +/- SEM) of infected grafts (5.4 +/- 0.5 kg) was decreased when compared with that of sterile, control grafts (9.0 +/- 0.9 kg). The decreased anastomotic tensile strength of infected grafts was the result of an inflammatory aortitis adjacent to the suture line. Only grafts infected with the study strain of bacteria demonstrated signs of infection. In 19 dogs, the graft infection was treated by graft excision, antibiotic administration, and in situ graft replacement (Dacron or polytetrafluoroethylene prostheses). After five weeks and 12 weeks, anastomotic tensile strength of polytetrafluoroethylene (10.6 +/- 0.6 kg) and Dacron (10.8 +/- 0.5 kg) replacement grafts was similar to that of uninfected control grafts. In situ replacement of vascular prostheses infected by S epidermidis can result in graft healing with normal anastomotic bonding.     

Effect of a selective thromboxane synthase inhibitor on arterial graft patency and platelet deposition in dogs

This study examined the effect of selective thromboxane synthase inhibition and nonselective cyclooxygenase inhibition on vascular graft patency and indium 111-labeled platelet deposition in 35 mongrel dogs undergoing carotid artery replacement with 4 mm X 4 cm polytetrafluoroethylene (PTFE) (one side) and Dacron (opposite side) end-to-end grafts. Aspirin-dipyridamole therapy improved one-week graft patency, from 46% in untreated dogs to 93% in treated dogs. Thromboxane synthase inhibition (U-63557A) improved graft patency in these dogs to 81%. Both drug treatments reduced platelet deposition on Dacron and PTFE grafts by 48% to 68% compared with control dogs. Dacron grafts accumulated significantly more platelets than PTFE grafts but had comparable patency rates. Low-dose aspirin therapy had no significant effect on either graft patency or platelet deposition. All treatment groups showed a 60% to 76% reduction in serum thromboxane B2, but only thromboxane synthase inhibitor treatment increased plasma 6-keto-prostaglandin F1 alpha by 100%. Selective thromboxane synthase inhibition improved small-caliber prosthetic graft patency to the same extent as did conventional cyclooxygenase inhibition in this preliminary study.     

Influence of endothelial cell seeding on platelet deposition and patency in small-diameter Dacron arterial grafts

Serial platelet deposition, surface topography, and patency were evaluated in control (N = 28) and endothelial cell-seeded (N = 28) small-diameter (4 mm inner diameter) USCI Dacron grafts implanted in the carotid and femoral arteries of dogs. All dogs received aspirin (325 mg) daily for 2 weeks starting 24 hours prior to graft implantation. Endothelial cell seeding was performed by mixing suspensions of autologous endothelial cells that had been enzymatically harvested from segments of external jugular vein with blood that was used to preclot the prostheses. The platelet deposition on each graft was quantitated by means of indium 111-labeled platelets and technetium 99m-labeled red cells in a dual-isotope platelet-imaging technique. Platelet deposition on seeded grafts 24 hours after implantation was significantly higher than on the controls (p less than 0.05). Two weeks after implantation platelet deposition on seeded prostheses had decreased to a level significantly lower than that on the controls and continued to decline on serial studies up to 7 months. In contrast to seeded grafts, platelet accumulation on control grafts dramatically increased after the withdrawal of aspirin therapy and was associated with a sharp rise in control graft thromboses. Gross and scanning electron microscopic evaluation of endothelial cell-seeded grafts after 1 month indicated complete neointimal coverage, whereas none of the control grafts explanted at 1 month or later exhibited a continuous neointimal lining. Cumulative 7-month patency for seeded prostheses was significantly higher than for the controls (96% and 29%, respectively; p less than 0.001). We conclude that endothelial cell seeding in combination with short-term aspirin therapy is a simple, reliable diameter Dacron prostheses. Abrupt withdrawal of aspirin therapy may be contraindicated in nonseeded control grafts because it results in increased platelet deposition and thrombosis.     

Accelerated Healing of Dacron Grafts Seeded by Preclotting with Autologous Bone Marrow Blood

> Studies have suggested that bone marrow-derived cells in the circulation may have the capacity and potential to endothelialize and heal vascular graft surfaces. We have investigated whether accelerated endothelialization could be achieved for Dacron grafts seeded by preclotting with bone marrow blood (BMB). Five 8 mm x 6 cm Dacron grafts seeded and preclotted with BMB and four controls preclotted with peripheral blood were implanted in the descending thoracic aorta (DTA) of mongrel dogs for 2 and 4 weeks. Two additional BMB DTA grafts were studied for 3 months. Five pairs of BMB and control grafts (4 mm x 6 cm) were bilaterally implanted into the carotids of dogs for 1 week and five pairs for 4 weeks. All grafts remained patent. BMB seeding/preclotting was a simple, effective method to accelerate early graft endothelialization without increasing thrombogenicity. Further studies are needed before clinical application can be recommended.