6-ketoprostaglandin-f1-alpha and Graft-Occlusion--Vascular

This animal study was designed to compare a collagen coated heparin bonded vascular graft (CHG) versus a collagen coated vascular graft (CG) regarding intraoperative blood loss and healing process. 24 polyester vascular grafts (12 CHG and 12 CG) of 6 mm in diameter and 5 mm in length were implanted between the common iliac and external iliac artery in 12 adult dogs. The grafts were explanted between the first and the sixth months which followed the implantations. The healing process was observed by gross examination, microscopic and scanning electron microscopic examination. Prostaglandin PGE2, TXB2, 6 keto PGF1 alpha and PGF2 alpha were measured by radioimmunologic assay from samples retrieved from the medium part of the graft. During implantation, there was no notable difference in blood loss through the graft. At the time of explantation, 20 grafts were patent (10 CHG, 10 CG). In both grafts, the healing process developed progressively between 2 and 6 months and 90% of the internal surface of the grafts were covered with endothelial like cells. At 6 months, the internal layer was thinner in heparinized graft. PGI2 secretion was found with the two types of grafts. In conclusion, the present study showed no difference in the blood loss or healing characteristic of CHG and CG except for a potentially thinner internal layer with CHG. Comparative studies in humans are necessary to evaluate the potential benefit of heparin bonded graft in clinical practice.

Topics: 6-Ketoprostaglandin F1 alpha; Anastomosis, Surgical; Animals; Blood Loss, Surgical; Blood Vessel Prosthesis; Collagen; Dinoprost; Dinoprostone; Dogs; Epoprostenol; Graft Occlusion, Vascular; Heparin; Iliac Artery; Microscopy, Electron, Scanning; Polyesters; Radioimmunoassay; Thrombosis; Thromboxane B2; Vascular Patency

To investigate the function and morphology of endothelial cell (EC) seeded grafts.. Experimental, open study.. Endoluminal release of prostacyclin (6-Keto-PGF1 alpha) and thromboxane B2 (TxB2), patency, EC coverage and cell identity.. In 12 sheep, segments of both carotid arteries were excised. On one side a seeded and on the other an unseeded dacron graft were inserted. After 3 months the grafts were excised. In grafts and arteries, the endoluminal release of 6-keto-PGF1 alpha and TxB2 was determined in a perfusion system. Scanning electron microscopy (SEM) and light microscopy were used to determine the EC coverage and cell identity.. Eight animals survived. Three seeded and two unseeded grafts were occluded. Prostacyclin release did not differ significantly between seeded and unseeded grafts and arteries, when the arteries were looked upon as one group. When the graft was compared with its corresponding artery, i.e. the artery it replaced, a significantly lower release was found in the unseeded group. Thromboxane release was undetectable in arteries but significantly higher in both graft groups. SEM revealed a cellular coverage of 75% in the seeded grafts and 50% in the unseeded (not significant). Light microscopy showed a patchy staining for Factor VIII-related antigen in some grafts in both groups.. Prostacyclin release in unseeded and seeded dacron grafts did not differ 3 months after implantation in sheep, except when the graft was compared with its corresponding artery. The significance of this remains to be settled. Seeded grafts did not have a higher proportion of endothelial coverage than unseeded grafts.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Vessel Prosthesis; Carotid Arteries; Cell Transplantation; Endothelium, Vascular; Epoprostenol; Graft Occlusion, Vascular; Male; Microscopy, Electron, Scanning; Platelet Aggregation Inhibitors; Polyethylene Terephthalates; Prosthesis Design; Sheep; Surface Properties; Thromboxane B2; Vascular Patency; von Willebrand Factor

It is known that vein grafts can be salvaged by clot removal, but patency rates are diminished. This study was designed to determine the effects of thrombus on vascular endothelium and the ability of the endothelium to recover normal function.. Thirty external jugular vein grafts were placed as bilateral femoral artery interposition grafts in 15 mongrel dogs and allowed to arterialize for a period of at least 12 weeks. Six control grafts were not exposed to thrombus (C-NT). Six other control grafts were exposed to thrombus for 7 days and removed, ie, allowed no in vivo recovery (C-T). The remaining 18 grafts in 9 canines were exposed to autologous thrombus for 5 days and then flow was restored. The right femoral graft was removed 7 days after thrombectomy and the left removed 30 days after thrombectomy. At the time of removal, the grafts were perfused with a balanced salt solution alone and then with arachidonic acid added to the same volume of the salt solution. Perfusates were collected at 5, 15, and 30 minutes. These perfusates were assayed for the presence of 6-keto-prosglandin F1 alpha (6-keto-PGF1(1 alpha)), a metabolite of prostacyclin (PGI2). Over the 30-day recovery period, the amounts of 6-keto-PGF1(1 alpha) produced with and without arachidonic acid added were compared to assess endothelial response. Electron micrographs of the endothelium of all vein grafts were compared to the assay findings.. When arachidonic acid was added to the perfusion system, there was a several fold increase in the production of 6-keto-PGF1(1 alpha) over baseline in all grafts allowed recovery. Grafts (C-T) that were allowed no in vivo recovery had no response to arachidonic acid. Ratios of 6-keto-PGF1(1 alpha) production with arachidonic acid stimulation to 6-keto-PGF1(1 alpha) production without stimulation were calculated to compare endothelial function. The electron micrographs showed the vascular endothelium to be severely injured after contact with thrombus, but recovered by 7 days.. This study suggests that the endothelium of canine vein grafts is injured by contact with thrombus for 5 days but can recover structure and function. This recovery is detectable at 7 days post-thrombectomy.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Disease Models, Animal; Dogs; Endothelium, Vascular; Graft Occlusion, Vascular; Jugular Veins; Microscopy, Electron, Scanning; Sodium Chloride; Thrombosis; Time Factors

Greyhounds (n = 38) were randomized to aspirin and dipyridamole (ASA + DPM), the thromboxane synthetase inhibitor (TSI) CGS12970 (CIBA-GEIGY) or placebo twice daily for 48 hours prior to bilateral implantation of femoral artery Dacron grafts. In-vivo 111In-platelet deposition on grafts was measured at 5 days and 2 months. Grafts were removed at 2 months when ex-vivo graft and arterial release of 6-ketoprostaglandin F1a (6-keto PGF1a) was measured by radioimmunoassay. Graft 6-keto-PGF1a was significantly increased by CGS12970 but ASA + DPM had no significant effect. ASA + DPM significantly reduced arterial 6-keto-PGF1a although this was marginally increased by CGS12970. Neither active treatment reduced in-vivo 111In-platelet deposition. Preservation of vascular or graft prostacyclin by thromboxane synthetase inhibitors may represent an alternative strategy in preventing prosthetic graft thrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Blood Vessel Prosthesis; Dipyridamole; Dogs; Drug Therapy, Combination; Female; Femoral Artery; Graft Occlusion, Vascular; Pyridines; Radiography; Random Allocation; Thromboxane-A Synthase

This study evaluated morphologic and functional characteristics of tissue reactions to compound prostheses of 69% absorbable polyglactin 910 (PG910) and 31% nonabsorbable polypropylene in the rabbit. Forty-two woven PG910/polypropylene prostheses (24 X 4 mm internal diameter) implanted into rabbit infrarenal aortas were harvested after 2 weeks to 12 months. Each explant was photographed and sectioned for light microscopy and transmission and scanning electron microscopy. Randomly selected explants underwent either compliance and bursting strength measurements or assays of production of prostacyclin and thromboxane metabolites by luminal surfaces of both regenerated conduits and normal control aortas in response to administered sodium arachidonate. Results showed 100% patency with no aneurysms and 2% stenoses (1 of 42 prostheses). Confluent endothelial-like cellular luminal surfaces covering oriented smooth muscle-like myofibroblasts comprised the inner capsules whose thicknesses stabilized at 1 to 2 months. Only residual polypropylene remained in the prostheses after 2 months. Compliance studies reflected a 0.65 mm (14%) change over a pressure range of 0 to 160 mm Hg. All regenerated prosthesis-tissue complexes had bursting strengths greater than the proximal perianastomotic native aortas, which burst between 600 and 2000 mm Hg. At 1 month the rate of production of 6-keto-PGF1 alpha per square millimeter of surface area of experimental segments was normal. Production of 6-keto-PGF1 alpha by experimental segments at 3 months had increased fourfold whereas thromboxane B2 (TxB2) production remained unchanged. The 6-keto-PGF1 alpha/TxB2 ratio increased from 1 to 4 months. This study demonstrates clinically efficacious morphologic, mechanical, and biochemical characteristics of PG910/polypropylene-elicited vascular prosthesis-tissue complexes.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Abdominal; Biocompatible Materials; Blood Vessel Prosthesis; Female; Foreign-Body Reaction; Graft Occlusion, Vascular; Microscopy, Electron; Microscopy, Electron, Scanning; Plastics; Polyglactin 910; Polymers; Polypropylenes; Rabbits; Tensile Strength

The ideal prosthetic vascular graft for the replacement or bypass of small vessels has not yet been developed. Many studies have documented the success of endothelial cell seeding in small-diameter Dacron grafts, but few have reported the application of this protocol to small-diameter PTFE grafts, and none have reported seeding small-diameter PTFE grafts in antiplatelet medicated dogs. The present study was undertaken to assess the efficacy of endothelial cell seeding of small-diameter (4 mm ID) PTFE (Gore-Tex) carotid artery interposition grafts in the antiplatelet medicated dog. Twenty-five male mongrel dogs were included in this study. In each dog one carotid artery was replaced with an endothelial cell seeded PTFE graft; the contralateral artery was replaced with a nonseeded graft. The in vivo progress of graft performance was evaluated from 1 to 4 weeks postoperatively. The endothelial cell seeded grafts achieved significantly higher patencies and mean thrombus-free surfaces than nonseeded grafts. Midgraft endothelium was identified only on the seeded grafts at 3 and 4 weeks, with a maximal luminal coverage of 10-12%. The measurements of prostacyclin (PGI2) production indicated that the antiplatelet agent therapy did inhibit endothelial cell cyclooxygenase. The presence of outer capsule vasa vasora, anastomotic pannus ingrowth, transinterstitial cellular ingrowth, and thin inner capsules characterized the endothelial cell seeded grafts in contrast to the nonseeded grafts. We conclude that enhancement of graft performance is achieved by combining both an antiplatelet regimen and endothelial cell seeding in small-diameter PTFE vascular grafts.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Blood Platelets; Blood Vessel Prosthesis; Dipyridamole; Dogs; Endothelium; Graft Occlusion, Vascular; Graft Survival; Male; Microscopy, Electron; Polytetrafluoroethylene; Vascular Patency

Long-term patency of coronary artery bypass grafts (CABG) with internal mammary artery (IMA) is better than with saphenous vein (SV) grafts. To determine if vascular prostacyclin (PGI2) produced by IMA might contribute to the improved outcome, we compared PGI2 generated by IMA and SV fragments from 26 patients undergoing CABG and tested the effect of preoperative, long-term ingestion of of aspirin. Fresh tissues were incubated in buffer +/- 25 mumol/L of sodium arachidonate at 37 degrees C for 5 minutes to stimulate PGI2 production, measured by radioimmunoassay of its major hydrolytic product, 6-keto-PGF1 alpha. Results were expressed in picograms of 6-keto-PGF1 alpha per milligram tissue wet weight for total PGI2 production by vascular segments and picograms per cm2 surface area for endothelial PGI2 production. Endothelial PGI2 production was compared for IMA and SV in template-stirring chambers that exposed only the luminal surface of the vessel, excluding underlying smooth muscle. Endothelial PGI2 production by IMA was significantly higher than production by SV under both basal (mechanical stimulation only 1436 +/- 224 versus 842 +/- 227 pg/cm2, mean +/- SEM, p greater than 0.05) and stimulated (25 mumol/L sodium arachidonate: 3343 +/- 347 versus 2032 +/- 465 pg/cm2, p less than 0.025) conditions in patients not receiving aspirin. For patients receiving aspirin, endothelial PGI2 production by IMA was significantly higher than production by SV in stimulated conditions (1382 +/- 526 versus 683 +/- 124 pg/cm2, p less than 0.05). Histologic examination of the tissue segments revealed intact endothelium after incubation in both IMA and SV. Thus a high capacity for PGI2 synthesis and diminished inhibition of PGI2 after aspirin were demonstrated for IMA compared with SV tissue and may be a factor in the improved patency of IMA grafts.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aspirin; Coronary Artery Bypass; Dinoprostone; Endothelium; Female; Graft Occlusion, Vascular; Humans; Male; Mammary Arteries; Middle Aged; Preoperative Care; Prostaglandins E; Saphenous Vein; Thoracic Arteries; Time Factors; Transplantation, Autologous

When the saphenous vein is used in the in situ position for arterial bypass surgery, it is associated with more optimal preservation of the endothelial lining and with improved graft patency compared with reversed vein grafts. However, it is not clear whether preservation of endothelial integrity persists after arterialization. The goal of this study was to establish whether preservation of the endothelium before arterialization is a critical factor in the development of late functional and morphologic abnormalities of autogenous vein grafts. Paired reversed and in situ vein grafts were created in 75 mongrel dogs. Veins to be used in the reversed position were excised and stored in either heparinized whole blood at 37 degrees C or saline solution at 4 degrees C. Veins were studied before and after arterialization. The veins were arterialized by anastomosis to the carotid artery and excised at intervals of 1 day to 12 weeks for studies of the luminal production of prostacyclin and thromboxane A2 in addition to luminal morphology. Before arterialization, normothermic whole blood preserved biochemical function of the endothelium significantly better than hypothermic saline solution, but not as well as the in situ vein procedure. Soon after arterialization, all three vein grafts showed significant functional and morphologic abnormalities consistent with injury of the vein graft. Morphologic healing of the endothelial monolayer progressed slowly back to normal; however, the biochemical capacity of the vein graft never matched that of the prearterialized vein, nor that of normal host arteries. Regardless of surgical technique, all vein grafts exhibited a period of abnormal structure and function, which exposed them to the risk of thrombogenesis. This period of potential leukocyte or platelet interaction with the vein wall could lead to release phenomena as well as proliferative changes in the vessel wall.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dogs; Endothelium; Epoprostenol; Graft Occlusion, Vascular; Microscopy, Electron, Scanning; Pressure; Saphenous Vein; Thromboxanes; Transplantation, Autologous; Vasa Vasorum

Prostacyclin (PGI2) production and platelet adhesion were studied in veins grafted into the arterial system of rabbits. Animal groups consisted of: no treatment; low dose aspirin (ASA) (0.5 mg . kg-1 X 24 h-1) plus dipyridamole (2 mg . kg-1 X 6 h-1); high dose ASA (40 mg . kg-1 X 24 h-1) plus dipyridamole (2 mg . kg-1 X 6 h-1); dipyridamole (2 mg . kg-1 X 6 h-1) alone. Results showed that vein grafts from animals treated with high dose ASA plus dipyridamole produced significantly less PGI2 than the other three groups (p less than 0.05 compared with the dipyridamole group; p less than 0.01 compared with the other two groups). In addition, there was significantly greater platelet deposition on the vein grafts from this high dose ASA group as compared to the low dose ASA group (p less than 0.05). By contrast, animals treated with dipyridamole alone had significantly less platelet deposition compared to both the control and high dose ASA groups (p less than 0.05). High dose ASA given to prevent thrombotic occlusion following coronary artery bypass grafting may, by reducing PGI2, result in enhanced platelet deposition. This in turn is likely to increase intimal hyperplasia as has been demonstrated previously with high dose ASA. Clinical studies, which have shown the early anti-thrombotic benefits of high dose ASA plus dipyridamole, have not measured graft intimal thickness. Since this process is an important cause of graft narrowing, ASA, in high dose, may adversely affect long-term graft survival.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Autoradiography; Carotid Arteries; Dipyridamole; Epoprostenol; Graft Occlusion, Vascular; Jugular Veins; Models, Biological; Platelet Adhesiveness; Rabbits