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Biomedical subjects

T Okoshi

Publications and source records attributed to T Okoshi.

46 records · Page 3Linked to original sources

Healing process of vascular prostheses seeded with venous tissue fragments.

Rapid neointima formation in fabric vascular prostheses seeded with autologous venous tissue fragments was examined. A piece of peripheral vein was minced into small fragments and stirred into 20 ml of saline. This tissue suspension was sieved through the wall of Dacron prostheses. The prostheses implanted in the descending aortae of dogs showed extremely rapid healing of the neointima. Endothelial cells lined the entire luminal surface within 14 days. There was no difference in the healing process between the area near anastomotic sites and the center.

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In vivo evaluation of porous versus skinned polyurethane-polydimethylsiloxane small diameter vascular grafts.

Two types of spongy polyurethane-polydimethylsiloxane (PU-PDMS) vascular grafts (1.5 mm ID, 450 microns wall thickness) were fabricated with either a skinned (SG) or a porous (PG) luminal surface and an open mesh filamentous external surface by a spraying, phase-inversion technique. Tubular membranes, 15-20 mm in length, were all implanted by the same surgeon as infrarenal aorta replacements in male Sprague-Dawley rats weighing 250-350 g (SG: n = 12, PG: n = 23). The patency rates at 2 weeks and 3 months were 0% (0/7) and 0% (0/1) for SG, 72% (8/11) and 8% (1/12) for PG. Because the wall structure of these grafts was relatively compact and did not provide enough communicating voids, another series of 15 highly porous luminal surface grafts was fabricated with a higher void to material ratio. These grafts (HPG) exhibited a 73% patency at 3 months, with a fully endothelialized surface. The authors conclude that a very open luminal surface structure, and a high wall porosity, are significant factors of graft patency in small diameter vascular prostheses made of a porous material.

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Neointima formation on an antithrombogenic cardiac wall substitute that can be reconstructed by host cells.

The authors previously reported on a new cardiac wall substitute (collagen-coated ultrafine polyester mesh, CUFP), which in an animal study showed satisfactory antithrombogenicity due to its hydrophilicity and excellent neointimal formation because it induced cell migration and proliferation. Both the ultrafine polyester mesh, and the collagen cross-linked with a hydrophilic reagent, have a special affinity for host cells. In the current study, the focus was on neointima formation on the CUFP, compared with that on glutaraldehyde-treated equine pericardium (GA graft), over longer time periods. Twenty-one CUFPs, and 19 GA grafts as controls, were implanted as patches in the right ventricular outflow tract in 40 dogs. In the CUFP at 28 days, a thin neointima, which was almost endothelialized, had been formed. Fibroblasts and vasa vasorum were seen inside both the neointima and the graft wall. The CUFP showed a white, shiny, smooth, thin, and uniform neointima with endothilialization at 486 days, and the neointima was firmly anchored by day 699. In the GA graft at 484 days, however, the neointima was partly detached from the GA graft and almost no fibroblasts had infiltrated the graft wall. Therefore, neointimal formation on the CUFP is almost completed within 1 month and maintained over the long term.

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Development of a soft, pliable, slow heparin release venous graft.

To prevent their collapse, a certain amount of stiffness is generally required for prosthetic venous grafts, so EPTFE grafts have been used. However, the native vein is pliable without any stiffness. We developed a soft and pliable graft that can maintain patency of the lumen because of its compliance. Fresh porcine ureter was incubated in a ficin solution to remove cell components and noncollagenous proteins. One percent protamine sulfate solution was injected into the ureter lumen to impregnate the inner surface. The ureter was then crosslinked with a 1% glutaraldehyde solution, dipped into a 1% heparin solution for 5 hours, and rinsed with distilled water. This procedure made the ureter very soft and pliable, and also conferred antithrombogenicity to the graft by heparinization. The grafts were implanted into the posterior vena cavae of 20 dogs and were removed from 1 to 878 days after implantation. Eighteen grafts were patent, but two grafts were occluded at the anastomotic site at 218 and 107 days, respectively. As a control experiment, nonheparinized grafts were implanted into 15 dogs; all were occluded with fresh thrombi. All the patent grafts kept their original elasticity, which allowed them to heave in unison with the heartbeat, and were similar in appearance to the native vena cava. Heparinization was effective in preventing thrombus formation. These results indicate that this type of graft is an ideal prosthesis as a venous graft, having physiologic properties such as compliance and antithrombogenicity.

Animals↗

Endothelialization of vascular prostheses by transplantation of venous tissue fragments.

A method to accelerate the endothelialization of vascular prostheses by seeding venous tissue fragments was developed. A piece of peripheral vein was obtained, chopped into small fragments, and stirred into 20 ml of saline, making a tissue suspension. This suspension was sieved through the wall of a highly porous vascular prosthesis (water porosity: 3,600-4,000). The prostheses, (7 mm ID and 5.7 cm in length) seeded with tissue fragments, were implanted into the thoracic descending aortae of 20 dogs, and were removed from 1 to 371 days after implantation. Ten prostheses, preclotted with fresh blood, were used as controls. In the seeded grafts, an infinite number of endothelial cells migrated and proliferated from the fragments. These had produced numerous capillaries by 5 days after implantation that had reached and opened onto the luminal surface of the prosthesis. From these openings, numerous endothelial cells spread out and formed colonies. With the increase in the size of the colonies, the inner surface was completely endothelialized within 5 weeks. This quick neointimal formation by seeding venous tissue fragments might be applicable to several artificial organs.

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A new bioprosthetic cardiac valve with reduced calcification.

A bioprosthetic cardiac valve cross-linked with a glycerol polyglycidyl ether polyepoxy compound (PC) was developed in order to reduce calcification and degeneration, which often occurs in bioprosthetic cardiac valves. Aortic valves harvested from dogs were treated with PC (PC valve). Right ventricle (RV)-pulmonary artery (PA) bypasses were placed in 12 dogs with PC-valved conduits, and the main PA was ligated. X-ray right ventriculography at 36 days (1 dog) and 37 days (1 dog) revealed an excellent open/close performance of the PC valve, and there was no visible thrombus in the valve. In our basic study, PC treated collagen gel disks implanted in the subcutaneous layer of growing rats showed remarkably less calcium deposition than did those treated with glutaraldehyde (GA). Biologic materials cross-linked with PC maintain their pliability, and become more hydrophilic and more hydrated than those cross-linked with GA. The hydrophilicity and hydration provide sufficient antithrombogenicity and a suitable environment for metabolism in the tissue fluid which contains oxygen, nutritive substances, and electrolytes, leading to inhibition of material degeneration. Therefore, PC valves are expected to show good valve function, sufficient antithrombogenicity, and excellent durability with less calcification, when compared to GA treated valves.

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Development of a small caliber biologic vascular graft: evaluation of its antithrombogenicity and the early healing process.

The authors previously showed that a small caliber xenograft using our crosslinking technique was applicable to aortocoronary bypass grafting. In this study of the graft, the antithrombogenicity and healing process was evaluated at an early stage after implantation. Fresh sheep carotid artery (3mm ID) was obtained and cross-linked with polyepoxy compounds, and then used as a small caliber vascular graft. The graft was white and soft. Six cm segments of the graft were implanted into the carotid arteries bilaterally in nine dogs. Sodium heparin was given during the surgery, but no anticoagulant was used postoperatively. Fifteen grafts from eight dogs were removed from 1 hr to 30 days after implantation, and 13 of 15 grafts were found to be patent. Two grafts, one at 3 days, and the other at 14 days, were occluded. The anastomotic area of the occluded grafts felt hard when touched from the outside. In one dog, the grafts were shown angiographically to be patent at 14 days after implantation, and this dog was kept for long-term observation. Macroscopically, no thrombus was observed on any of the patent grafts. Microscopically, the inner surface near the anastomotic lines was covered with endothelial cells, and infiltration of fibroblasts was observed from the outside 7 days after implantation. No foreign body reactions were seen around the graft. After 30 days of implantation, a thin layer of plasma protein at the middle of the graft was observed by scanning electron microscopy (SEM). From these observations, it was concluded that the grafts exhibited satisfactory early antithrombogenicity and healing after implantation.

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Development of a small-caliber vascular graft with antithrombogenicity induced by extreme hydrophilicity.

A small-caliber vascular graft with an excellent patency rate, which has satisfactory antithrombogenicity due to high hydrophilicity, has been developed. It is hemostatic at the anastomotic site and has an affinity for endothelial-like cells, smooth musclelike cells, and fibroblasts. Fresh carotid artery with an ID of 2.5 to 3.0 mm was obtained from a dog and sonicated to induce destruction of the cell components. It was then cross-linked with a hydrophilic polyepoxy compound. As controls, glutaraldehyde (GA) treated grafts were prepared. Twenty-one dogs were used, 14 for the new graft and the other 7 as controls. A segment of the graft, 6 cm in length, was implanted into the carotid artery. Sodium heparin was given during surgery, but no anticoagulant was used thereafter. The compliance of the new graft was similar to that of the native artery. No excessive bleeding was noticed at the anastomotic sites. The patency rate was 70.8% during the longest observation period of 145 days, but was only 10% in the controls. Microscopic observation revealed that by the seventh day after implantation, endothelial-like cells had appeared near the anastomotic lines on the inner surface of the new graft; smooth musclelike cells were observed on the 38th day after implantation. From these results, there is a good possibility that this new graft, with its many advantages, may be used clinically.

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Development of an antithrombogenic cardiac wall substitute which can be reconstructed by infiltration of host cells.

Various kinds of materials, such as glutaraldehyde-treated pericardial heterografts, have been used as a cardiac wall substitute. Some problems were encountered with their use. We clarified these problems in animal experiments and developed a new cardiac wall substitute to overcome them. As one of the best cardiac wall substitutes obtainable at present, glutaraldehyde-treated equine pericardium (Xenomedica, GA-graft), was sutured as a patch in the right ventricular outflow tract (Group 1: 16 dogs). A new cardiac wall substitute, which is composed of collagen-coated polyester mesh (CUFP), was sutured in the same fashion (Group 2: 19 dogs). The problems clarified in the GA graft were insufficient antithrombogenicity and poor healing of the neointima and the graft wall. The CUFP had sufficient antithrombogenicity and good healing quality as a cardiac wall substitute. CUFP should be rapidly infiltrated by host cells, to become a kind of host organ and therefore not degenerate with long-term use.

Animals↗

A functional neointima with regularly arranged smooth muscle cells in a fabric vascular prosthesis transplanted with autologous venous tissue fragments.

Regular arrangement of smooth muscle cells underneath an endothelial cell layer was observed in the neointima of a fabric vascular prosthesis treated with new technology to accelerate endothelialization, i.e., transplantation of autologous venous tissue fragments in the graft wall. This finding indicated that the neointima has a vital function as the intima of the blood vessel. A canine left jugular vein was minced and stirred into 20 ml of saline containing 1,000 IU heparin. It was injected with pressure into a fabric prosthesis (4 mm inner diameter [ID], 3.5 cm in length, Water porosity: 4,000 ml) to create the tissue fragmented, heparinized graft. The graft was implanted into the same animal from which the jugular vein was taken. Forty tissue fragmented heparinized (TFH) grafts were implanted in both carotid arteries of 20 dogs and explanted from 1 hr to 400 days after implantation. In this study, the neointimae of the grafts implanted for more than 1 month are analyzed, with a focus on the arrangement of smooth muscle cells in the neointima. A circumferential arrangement of smooth muscle cells with a thin layer of longitudinally arranged cells underneath was seen in the neointimae, which resemble the arrangement of smooth muscle cells in the natural arterial wall. Some areas had a thin smooth muscle cell layer in the longitudinal direction just under the endothelial cell layer. At anastomotic sites, they ran in parallel rows in the longitudinal direction. The authors previously clarified that the smooth muscle cells arrange in parallel rows in the direction of strain caused by tensile stress.(ABSTRACT TRUNCATED AT 250 WORDS)

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