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The process of reendothelialization was studied in a deendothelialized 3 cm segment of the canine descending thoracic aorta from which peripheral endothelial cell ingrowth had been prevented by impervious prosthetic graft sleeves. Three preparations were studied: (1) removal of only the endothelial cells, accomplished by flow surface drying and balloon catheter denudation, (2) removal of the superficial portion of the nonvasal media, accomplished by endarterectomy to a depth of 200 to 300 micron, and (3) removal of the entire inner (nonvasal) media, accomplished by endarterectomy to a depth of 500 to 600 micron to reach the outer (vasal) media. A total of 44 specimens were studied after implantation periods of 7, 14, 28, and 56 days. In all cases endothelial cell ingrowth from the host aorta into the test specimen was prevented by the impervious graft sleeves. In the deep endarterectomy group there were scattered areas of reendothelialization at 1 week, extensive reendothelialization at 2 weeks, almost complete reendothelialization at 4 weeks, and confluence by 8 weeks. However, in the superficial endarterectomy group scanning electron microscopy showed scattered areas of factor VIII/von Willebrand factor (FVIII/vWF)-negative, endothelial-like cells at 4 weeks, whereas at 8 weeks most of the surface was covered by endothelial cells identified by FVIII/vWF. In those specimens subjected to balloon catheter removal of endothelial cells only, reendothelialization was not seen, even at 8 weeks.

This study was designed to establish the influence of the recipient's thrombotic potential on the patency of small-caliber prostheses and to evaluate the subsequent improvement of graft performance by medicinally altering the prostaglandin balance in subjects predisposed to graft occlusion. Mongrel dogs were pretested and classified as low and high responders according to their thrombotic potential, measured as prostaglandin metabolite balance and platelet aggregability. High responders were randomly divided into two groups. Those assigned to serve as the medicated subjects were pretreated 1 week before surgery with a single oral daily administration of combined dazmegrel (UK-38,485) and aspirin in equal dosages of 3 mg/kg. Medication was continued throughout the experiment. Dacron grafts were implanted bilaterally in the carotid artery site in all subjects. Following a 3-week implantation period, the patency rate for the group with low thrombotic potential was 100%. In the animals with high thrombotic potential the patency rate was 10% for nonmedicated subjects and 100% for medicated subjects. These data support the concept that the thrombotic potential largely determines the capacity of the recipient's blood to thrombose small-caliber prostheses. Effective medicinal alteration of prostaglandin balance results in exceptionally increased patency of synthetic grafts.

The effects of tissue ingrowth on the compliance of porous Dacron grafts were studied in 8 mm external-velour warp-knit Dacron grafts implanted in the canine descending thoracic aorta. The compliance of these grafts was measured before implantation and after implant periods of two weeks and one, two, four, and six months. Compliance, which initially was 0.043 +/- 0.008% mm Hg, decreased less than 10% after implantation (no statistical difference at p less than 0.05). No anastomotic neointimal hyperplasia was observed. Although the total thickness of the graft wall increased two- to three-fold after implantation, the benign healing process observed in this study had very little influence on graft compliance followed to six months.

Because repeat sternotomies are becoming much more prevalent with repeat coronary bypass operations, prevention of direct adhesions of the heart and grafts to the back of the sternum by use of synthetic or xenograft material to close the pericardiotomy has become a matter for investigation. In this study bovine and equine glutaraldehyde-processed xenografts were implanted bilaterally in dogs for implant intervals of 6 weeks and 3, 6, 9, and 12 months. The bovine and equine xenografts both performed well in resisting the adhesion of the heart to their inner surfaces and less well in resisting adhesion of the lung and chest wall to their outer surfaces. The bovine xenograft had a higher percentage of adhesion-free surface on all the surfaces evaluated; however, one of our 12-month bovine pericardial xenograft implants exhibited significant multifocal calcific degeneration. Although pericardial xenografts generally have performed well when implanted in the dog, Gallo, Artiñano, and Duran recently expressed concern about their performance in humans. Along with our finding of calcification, their concern suggests a cautious approach to clinical application.

Organization of a venous thrombus proceeds much faster than that of an arterial thrombus. Two different double-ligation procedures were used for study of the time sequence of thrombus organization by the vascularized (in situ) and devascularized (dissected) walls of the external jugular vein and common carotid artery in 21 mongrel dogs. Blood in the ligated segments of the in situ veins remained mostly fluid. In these segments, intimal hyperplasia was observed after 4 weeks with apparent preservation of an endothelial lining. However, in the dissected veins, the trapped blood rapidly thrombosed. Remarkable cell proliferation quickly occurred in these dissected walls with rapid invasion of the thrombus to achieve complete organization by 4 weeks. In contrast, a thrombus formed in the ligated segments of all arteries, whether in situ or dissected, and organization was much slower, requiring about 4 months for completion. Full-wall viability was maintained in 100% of the in situ veins and in 95% of the devascularized veins, but inner wall viability was lost in 30% of the in situ arteries and in 95% of the devascularized arteries.

This study characterizes the effect of dazmegrel, a thromboxane synthetase inhibitor, on platelet function in the dog and introduces its potential use in combination with aspirin therapy. Ex vivo testing of dazmegrel alone was performed with three dosages and three administration regimens. Platelet aggregation response, malondialdehyde formation and prostaglandin metabolites generation were evaluated. To maintain complete thromboxane A2 inhibition, dazmegrel had to be given 3 times per day at dosages of not less than 6 mg/kg. The same result was achieved with a single daily administration of combined dazmegrel and aspirin in equal dosages of 3 mg/kg. Dazmegrel, both alone and with aspirin, increased and sustained heightened levels of prostacyclin, unlike the simultaneous inhibition of both prostaglandin metabolites seen with aspirin therapy alone. Because the combination of dazmegrel and aspirin effectively blocks thromboxane A2 formation and also enhances prostacyclin formation, the synergistic action of these agents increases their combined antiplatelet effect to a level not attainable by either agent alone. The significance of this combined therapy warrants further experimental study and may soon merit clinical trial for the prevention of stroke and other major thrombotic complications.

Six external velour (Bionit C. R. Bard, Inc.; Billerica, MA) and 11 double velour (Microvel Meadox Medicals, Inc.; Oakland, NJ) warp-knit Dacron grafts with lengths of 6 cm and diameters of 8 mm were implanted in the canine upper descending thoracic aorta for 56 days. Differences were observed: four of 11 double velour grafts developed major perigraft hematomas, while none of the external velour grafts exhibited this complication. Healing of the external velour grafts was virtually complete (average full wall healing and endothelial-like cell coverage of 97.0%, SD 5.9%) in contrast to the seven (of 11) double velour grafts that were free of perigraft hematoma (average full wall healing and endothelial-like cell coverage of 40.9%, SD 20.9%).

Dacron prostheses with differing degrees of inner wall filamentousness were implanted in the canine descending thoracic aorta for 56 days (n = 14) and the carotid arteries for 21 days (n = 40). In the thoracic aorta the healed inner capsule of 8 mm internal velour grafts was approximately three times as thick as the inner capsule of external velour knitted prostheses. However, the early patency and rapidity of healing of these two types of prostheses were essentially the same. In the carotid arteries the patency of the 4 mm external velour prostheses was greater than that of the internal velour prostheses and the mean thrombus-free surface area of the external velour grafts was significantly greater than that of the internal velour grafts. These observations suggest that an internal velour surface is not deleterious to early patency in a large-caliber, high-flow artery but that it may be in a small-caliber, low-flow artery.

The influence on healing of three materials for closure of interstices in a macroporous Dacron arterial prosthesis were evaluated by 56-day implantation in the canine descending thoracic aorta. The materials studied were: the nondenatured fibrin deposited as a result of a 4-step preclot with autogeneic blood (n = 6), heat-coagulated autogeneic blood deposited by autoclaving the blood-soaked prosthesis (n = 6), and cross-linked human albumin (n = 6). Healing of autogeneic fibrin was superior with little difference between the other two materials.

The study objective was to determine the optimal water porosity for a warp-knit, externally veloured Dacron arterial prosthesis. Preclotting efficiency, surgical handling characteristics, thrombogenicity, and 56-day healing in the descending thoracic aorta of mongrel dogs were measured for seven different arterial prostheses of the same basic design constructed to test the influence of decreased porosity produced by increased yarn denier at a constant needle density. The six prototypes tested were 160, 180, 200, 220, 240, and 280 denier. The 140 denier prosthesis (Bionit, C. R. Bard, Inc., Billerica, MA) served as the control. The water porosity of these prostheses varied from 2036 ml/cm2/min at 120 mmHg for the control to 286 for the 280 prototype. The preclotting efficiency increased with decreased water porosity and with increased outer-wall filamentousness. Desirability of surgical handling characteristics decreased with lowered water porosity, while the degree of outer-wall filamentousness had little influence. All the prostheses showed excellent through-wall healing at 56 days, including endothelialization. The 160 prototype represented an optimal blend of high preclotting efficiency, desirable surgical handling characteristics, and excellent 56-day healing. These studies are pertinent to the future development of porous, warp-knit Dacron arterial prostheses.

An in vitro method for comparing the penetration of bovine fibroblasts seeded on the external surface of porous vascular prostheses was devised. The effects of water porosity reduction and differing manufacturing constructions (warp-knit Dacron, woven Dacron and polytetrafluoroethylene) on the ability of the bovine fibroblasts to penetrate transmurally was investigated. Of the warp-knit external-veloured Dacron prostheses, the highest porosity 140-denier prototype had the highest luminal surface cell count and the lowest porosty 280-denier prototype the lowest luminal surface cell count. The intermediate prototypes had values between these two extremes. The woven Dacron prostheses, which were of even lower porosity but with a much thinner wall, had cell counts midway between the 140-denier and the 280-denier prototypes. The microporous polytetrafluoroethylene prostheses did not allow fibroblast penetration despite adherence of cells to the outer surface. These findings agree with in vivo healing studies of the same materials in the descending thoracic aorta of the dog, demonstrating that this rapid in vitro assay method can help predict the healing potential of a vascular prosthesis.

Eight currently used arterial prostheses with differing constructions and materials were implanted in the descending thoracic aorta of mongrel dogs. The prostheses were Gore-Tex (polytetrafluoroethylene), DeBakey Woven, Cooley Woven, Meadox Woven Double Velour, Cooley Knitted Double Velour, Microvel, Vasculour II, and Bionit II. Five series of these eight prostheses were serially implanted in heparinized subjects. During the 40 implantations, attention was focused on three major characteristics: preclotting efficiency, surgical handling characteristics, and healing. Gore-Tex is impervious to blood. The DeBakey and Cooley woven grafts are nearly so. The remaining prostheses required preclotting. The Meadox Woven Double Velour became impervious after two preclotting steps, the Cooley Knitted Double Velour and the Bionit II required three, and the Vasculour II and the Microvel required four. The surgical handling characteristics of the knitted prostheses clearly surpassed those of the DeBakey and Cooley woven and Gore-Tex prostheses. Although the Meadox Woven Double Velour prosthesis had better conformability than the nonveloured woven, the tendency of its cut edge to fray was more pronounced. Healing was much more advanced in the knitted and woven prostheses than in the Gore-Tex.

To assess whether ultrasonography is valuable in the diagnosis and management of patients with complete chest X-ray opacification of hemithorax, chest ultrasonography was conducted in 65 patients. There were 54 patients (83.1%) with massive pleural effusion with or without other pathology, six (9.2%) with tumors, two (3.1%) with organized fibrothorax, two (3.1%) with consolidation or atelectasis and one (1.5%) with pseudocyst of the pleura in the sonographic diagnosis. Sonography differentiated effusion from tumor, consolidation and fibrosis. The effusion showed a hypoechoic area with floating fibrin strands and changed shape on respiration. The tumor revealed a homogeneous iso- or hypoechoic mass with a sharp margin. Consolidation or atelectasis showed a lobar or segmental area of heterogeneous isoechoic density with air-bronchogram. The pleural showed an area of hypoechoic density without floating fibrin or a changed shape on respiration. In 24 (37%) patients we could demonstrate complex pathology addition to the pleural effusion. Twenty-one patients had a hidden tumor beneath the effusion. Three patients had consolidation or atelectasis with effusion. In 13 patients, aspiration biopsy was performed under ultrasonic guidance from the tumor and the histological diagnosis was confirmed in 12 patients. We conclude that ultrasonography is a very useful, noninvasive tool in the differential diagnosis of complete chest X-ray opacification of hemithorax. Complex pathology is also easily detected by sonography. Sonographic findings can also be used as a guideline for an appropriate approach to the patient's management.