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A 75-year-old man diagnosed as having ischemic dilated cardiomyopathy, congestive heart failure and mitral regurgitation underwent left ventricle volume reduction operation (Batista), coronary bypass grafting and mitral valve replacement because myocardial infarction had developed at lateral, inferior and small area of apex wall, not at interventricular septum. Left ventricular endodiastolic volume index and left ventricular endosystolic volume index decreased from pre-operative values of 155, and 128 ml/m2 to post-operative values of 113, and 82 ml/m2, respectively. Left ventricular ejection fraction increased from a pre-operative value of 17% to a post-operative value of 27%. This evaluation was performed by myocardial scintigraphy (quantitative gated spect: QGS). This method was bloodless and useful for determination of indication of left ventricle volume reduction surgery including Batista operation and pre- and post-operative evaluation of this type of surgery. Today, Batista operation is, generally speaking, performed for non-ischemic dilated cardiomyopathy. In this case, however, Batista operation was applied to ischemic dilated cardiomyopathy and was very effective.

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Recent researches on vascular grafts are introduced in this paper. A goal in development of small diameter vascular graft is to obtain their long-term patency and various approaches have been tried. On the other hand, renovation has been made aiming at further refinement of middle to large diameter vascular grafts although their long-term patency have been almost satisfactory. Endothelialization at graft inner surfaces is a very important key to achieve long-term patency and to prevent graft infection. Tissue engineering, which includes technologies on proteins, cells, genes, adhesive proteins, cytokines and so on, has been recently induced in development of vascular grafts. It is expected that excellent vascular grafts would be fabricated in the near future.

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Vascular prostheses coated with collagen carefully prepared to avoid contamination were tested to see if it could induce endothelial cell lining throughout the graft surface in a natural way. The collagen fibers were succinylated. Hydrogel produced with the succinylated collagen was used for the sealant to reduce the amount of solid substance. To avoid contamination and the side effects of chemical reagents, the collagen thermally crosslinked under sterile conditions. A suspension of the collagen fibers was enmeshed in the interstices of Dacron fibers of fabric prostheses, which were then thermally crosslinked at 130 degrees C for 20 h. The prostheses were porous when the collagen fiber network was dry. Under wet conditions, however, the water permeability of the grafts was reduced to 0.1 ml/min from the 1,250 ml/min of the original prostheses. Three weeks after implantation in the abdominal aortas of dogs, 81.2 +/- 11% of the luminal surface was macroscopically thrombus free, and 56 +/- 14% was endothelialized. More than 95% of the coated collagen had been absorbed. Numerous fibroblasts had migrated into the graft walls, and capillary blood vessels had infiltrated the inside of the graft walls without foreign body reaction. In the controls, thrombus free areas averaged 9.0 +/- 5%, and endothelialized areas averaged 5.2 +/- 4%. Many giant cells, plasma cells, and lymphocytes had migrated into the graft walls, but no fibroblasts. These results suggest that rapid endothelialization is possible when clean collagen is used.

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Preparation of cells and tissues for bioartificial vascular grafts is discussed from the viewpoint of tissue engineering. In general, a neointima is not formed on vascular prostheses except at the anastomotic sites. Graft surfaces do not heal and are covered with fresh thrombi for a long period of time after implantation. The delayed healing is, so to speak, an intractable ulcer of the vascular wall. To overcome this problem, we have developed a tissue fragment transplantation method. We consider that neointima formation of vascular prostheses after implantation is a product of tissue engineering in vivo. Therefore, 3 essential elements for tissue engineering, i.e., cells, extracellular matrices, and cytokines, are required for neointima formation. Synthetic vascular prostheses lack one or more of these elements. In this study we demonstrated a standard healing process of fabric vascular prostheses and an antithrombogenic polymer graft using animal models. Then we showed the tissue fragment transplantation method using venous tissues, adipose tissues, and bone marrow. This method provided the 3 essential elements to the prostheses. To allow these elements to be actively engaged in neointima formation, we treated cells and tissues as clumps without enzymatic digestion. We also took advantage of the in vivo environment. With the results we demonstrate our way of thinking in relation to bioartificial vascular grafts.

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We review recent findings in human brain imaging, for example, which brain areas are used during perception of colors, moving objects, human faces, facial expressions, sadness and happiness etc. One study used fluorine-18-labeled deoxyglucose positron emission tomography (PET) in patients with unipolar depression and bipolar depression, and found hypometabolism in the left anterolateral prefrontal cortex. Another study reported increased regional cerebral blood flow in the amygdala in familial pure depressive disease. Using 11C-glucose PET, we reported that the glutamic acid pool was reduced in cortical areas of the brain in patients with major depression. We also found that the thalamic and cingulate areas were hyperactive in drug-naive (never medicated) acute schizophrenics, while the associative frontal, parietal, temporal gyri were hypoactive in drug-naive chronic schizophrenics. Brain biochemical disturbances of schizophrenic patients involved glutamic acid, N-acetyl aspartic acid, phosphatidylcholine and sphingomyelin which are important chemical substances in the working brain. The areas of the thalamus and the cingulate which become hyperactive in acute schizophrenic patients are important brain areas for perception and communication. The association areas of the cortex which become disturbed in chronic schizophrenia are essential brain areas in human creativity (language, concepts, formation of cultures and societies) and exist only in human beings.

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Blunt trauma followed by aortic valvular insufficiency is a rare occurence. In one case, a male high-school student who had sustained a non-penetrative chest injury suffered from aortic regurgitation resulting from the rupture of the normal aortic valve. A sizable tear in the non-coronary cusp caused aortic insufficiency. The case was treated successfully by surgical replacement of the aortic valve with a No. 21 SJM prosthesis.

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This article points to the importance of penetrating micropores through the graft wall to minimize thrombosis and to enhance endothelialization in small diameter polymer skin coated vascular grafts. Four types of spongy polyurethane-polydimethylsiloxane vascular grafts (PUG) fabricated by a spray, phase-inversion technique, 1.5 mm inner diameter, 1.5-1.9 cm in length, were implanted end-to-end in the infrarenal aorta of 26 adult rats. Some had a continuous inner skin and a hydraulic permeability (HP) of 0 ml/min/cm2/ 120 mmHg (PUG-S-O). Some had an inner skin with varying amounts of isolated penetrating micropores and a mean hydraulic permeability of 11 (PUG-S-11), 37 (PUG-S-37), or 58 ml/min/cm2/120 mmHg (PUG-S-58). Twelve PUG-S-O, 6 PUG-S-11, 4 PUG-S-11, and 4 PUG-S-58 were evaluated between 2 hr and 3 months after implantation. All PUG-S-O occluded soon after implantation. The PUG that had a HP of more than 11 ml/min/cm2 showed acceptable patency. However, endothelialization was limited to anastomoses in patent PUG-S-11. In contrast, the patent PUG-S-37 and PUG-S-58 were largely endothelialized. In all patent grafts at 3 months, numerous host cells had migrated, and newly formed capillaries were seen in the voids of the graft wall, which appeared moderately to highly cellular. In conclusion, it appears that penetrating micropores through the graft wall increase patency and that a highly porous structure is needed to achieve extensive endothelialization in small diameter polymer skin coated vascular grafts.

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Angiogenesis by basic fibroblast growth factor (bFGF) is important for endothelialization in vascular prostheses and is significant from shortly after implantation. Canine adipose tissue was resected, minced into fragments, and suspended. This mixture was sieved through the wall of a fabric vascular prosthesis. Tissue-fragmented grafts (TF-grafts, 6 mm internal diameter, 6 cm long) were implanted into the abdominal aortae of four dogs, and four preclotted grafts were used as control subjects. Grafts were removed at 1-7 days after implantation. Removed grafts were evaluated microscopically, immunohistologically, and by scanning electron microscope. At day 1, a thrombus layer was on the TF-graft lumen. At day 3, cell proliferation and migration were observed. At day 5, endothelial-like cells were extending onto the luminal thrombus. Cell proliferation around the fragments was active, and those cells were bFGF positive. In the control subjects, at day 7, the perigraft tissue was bFGF positive, whereas no endothelialization on the lumen or no capillary infiltration into the graft wall was observed. Furthermore, bFGF was negative in the sites of thrombus and infection. These results demonstrate that endogenous bFGF is important for endothelialization due to angiogenesis in fabric vascular prostheses, whereas thrombus and infection might have a negative effect.

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A 62-year-old man was given a diagnosis of small cell lung cancer, and received 6 courses of combination chemotherapy (PE therapy) composed of cisplatin (80 mg/m2, day 1) and etoposide (100 mg/m2, days 1, 2, 3). Multiple brain metastases were found, and whole brain irradiation (44 Gy) was given. Eleven months after radiotherapy, he suffered from dizziness and abnormal gait. Enhanced CT of the head showed slight enlargement of the lateral ventricles and markedly low density of the white matter, but no evidence of intracranial tumor involvement. A magnetic resonance scan (axial T2-weighted) showed symmetric extensive hyperintensity in the white matter. Treatment-related leukoencephalopathy caused by the PE therapy and whole brain irradiation was diagnosed. He was alive 8 months after the appearance of neurological symptoms, without recurrence of lung cancer. A search of the literature revealed no previous report of leukoencephalopathy related to PE therapy.

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Six types of skinned and microporous vascular prostheses (1.5 mm ID) with different hydraulic permeabilities (HP) were fabricated with either a polyurethane polydimethylsiloxane (PU-PDMS) or a polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE) by the spray phase inversion technique: skinned PU-PDMS grafts with an HP of 0 ml/min/cm2 (PU-PDMS-S-0), microporous surfaced PU-PDMS grafts with an HP of 2.7 ml/min/cm2 (PU-PDMS-2.7), microporous surfaced PU-PDMS grafts with an HP of 39 ml/min/cm2 (PU-PDMS-39), poled skinned PVDF-TrFE grafts with an HP of 0 ml/min/cm2 (poled PVDF-TrFE-S-0), poled microporous surfaced PVDF-TrFE grafts with an HP of 41 ml/min/cm2 (poled PVDF-TrFE-41), and unpoled microporous surfaced PVDF-TrFE grafts with an HP of 41 ml/min/cm2 (unpoled PVDF-TrFE-41). Straight segments of these grafts (1.5-2.2 cm in length) and one loop PU-PDMS-39 (10 cm in length) were implanted in the rat infrarenal aorta. Graft surface morphology and wall porosity as reflected by hydraulic permeability were the main determinants of early patency and completeness of healing including endothelialization.

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A vascular prosthesis that can induce a neointima similar to a natural arterial wall is reported. The authors have developed a sealing method using autologous tissue fragments. The sealed graft showed many advantages, with characteristic neointima formation in an animal study. The grafts were implanted in the thoracic descending aortae of 40 dogs and were removed from 1 hour to 608 days after implantation. Another 40 dogs, used as controls, had a fabric graft implanted using the preclotting method. The luminal surface of the sealed graft was completely endothelialized and the original adipose tissue fragments were absorbed within 1 month. Smooth muscle cells infiltrated and proliferated at the same time as endothelialization took place. Most of the smooth muscle cells were arranged in parallel rows and oriented circumferentially within the graft. At 1 month, elastic fibers appeared around the smooth muscle cells near the anastomotic sites. In the long-term specimens, these elastic fibers constituted a fine lamina in the neointima. Intimal hyperplasia and degenerative changes in the neointima were not observed. These results indicated that the sealing method could induce a very stable neointima with a smooth muscle cell layer and elastic laminae similar to a natural arterial wall within a short period of time throughout the graft wall, with maintenance of the neointima for a long period of time after implantation.

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We investigated the alteration of glycosaminoglycans (GAGs) induced by recombinant human tumor necrosis factor alpha (rhTNF alpha) using confluent cultures of bovine aortic smooth-muscle cells, bovine aortic endothelial cells, Chang liver cells and porcine kidney LLC-PK1 cells. It was found that the incorporation of both [35S]sulfate and [3H]glucosamine into GAGs in the trypsinate fraction of the cell layer was significantly decreased by rhTNF alpha in vascular smooth-muscle cells and vascular endothelial cells; the incorporation of [35S]sulfate was increased but that of [3H]glucosamine was unchanged in Chang liver cells; the incorporation of both [35S]sulfate and [3H]glucosamine was increased by rhTNF alpha in LLC-PK1 cells. In the conditioned medium, the incorporation of both [35S]sulfate and [3H]glucosamine was not greatly changed by rhTNF alpha in all tested cell types. Characterization of GAGs revealed that each cell type uniquely altered its GAGs after rhTNF alpha treatment; the cytokine-induced alteration of each GAG component was not necessarily the same among different cell types. It was therefore concluded that rhTNF alpha-induced alteration of GAGs is dependent upon cell type.

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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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We have previously demonstrated rapid and complete endothelialization in synthetic fabric vascular prostheses that have been pretreated with autologous venous tissue fragments. However, significant thrombogenicity has been a major problem when this method has been applied to small-diameter grafts. By masking the positively charged collagen fibrils in the tissue fragments with negatively charged heparin, we were able to overcome this problem. A canine jugular vein was resected, minced into tissue fragments, and suspended. This mixture was sieved through the wall of a highly porous vascular prosthesis with a water porosity value of 4,000 ml/cm2 per minute by pressurized injection, which caused the tissue fragments to be trapped in the graft wall. Tissue-fragmented grafts (7 mm inside diameter, 5.7 cm long) were implanted into the thoracic aorta of 35 dogs. In addition, tissue-fragmented grafts of small diameter (4 mm inside diameter, 3.5 cm long) were pretreated with heparin and implanted into the carotid arteries of 16 dogs (32 grafts). Preclotted grafts without tissue fragmentation were implanted into the thoracic aorta (25 dogs) and carotid arteries (6 dogs, 12 grafts) as controls. Grafts were explanted from 1 to 495 days after implantation. New arterial wall formation was complete throughout the tissue-fragmented grafts within 2 weeks; however, in the control grafts, neointima formation was limited to the anastomotic sites even after 2 months. Twenty small-caliber tissue-fragmented grafts that were pretreated with heparin in the carotid position were patent, but all the control grafts were occluded within 1 week. These results demonstrate that neointima formation can be enhanced in synthetic fabric prostheses; furthermore, long-term patency of vascular grafts of small caliber is possible in dogs with this tissue-fragmentation technique.

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Two types of spongy polyurethane-polydimethylsiloxane blend (Cardiothane 51, Kontron Instruments, Inc., Everett, Mass.) vascular grafts with an internal diameter of 1.5 mm were fabricated by a spray, phase-inversion technique. Low-porosity grafts with hydraulic permeability of 2.7 +/- 0.4 ml/min per square centimeter and medium-porosity grafts with hydraulic permeability of 39 +/- 8 ml/min per square centimeter displayed good handling properties and suturability. Twelve straight low-porosity grafts, 17 straight medium-porosity grafts (1.5 to 2.0 cm in length), and one loop medium-porosity graft (10 cm in length) were implanted by the same surgeon end to end in the infrarenal aorta of 30 male Sprague-Dawley rats. Three months after implantation, patency was 8% for low-porosity grafts (1/12) and 76% for straight medium-porosity grafts (13/17). The loop medium-porosity graft was also patent. The sole patent low-porosity graft showed neointimal hyperplasia and incomplete endothelialization. All but one of the patent straight medium-porosity grafts showed a glistening and transparent neointima with complete endothelialization and no anastomotic hyperplasia. The loop medium-porosity graft displayed endothelialization from each anastomosis and in many islands in the middle portion of the graft, totalling 47% of the luminal surface by morphometric analysis. Thick mural thrombus, anastomotic hyperplasia, or aneurysm formation were not observed in any patent medium-porosity graft. These data indicate that in the rat aortic replacement model it is possible to achieve patency and a high degree of endothelialization in very small-diameter prostheses of appropriate porosity.

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The spectral properties of a LP(01) ? LP(02) mode converter by using a photoinduced fiber grating are investigated. A fiber with given parameters is considered, and the wavelength dependence of power conversion between the two modes is calculated. The results show that the spectrum can be narrowed by selecting the operating wavelength close to the cutoff wavelength of the LP(02) mode. The methods for obtaining a mode converter with a broadband spectrum and a mode converter with a spectrum having two peaks are also discussed.

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A method was developed to obtain rapid endothelialization of a fabric vascular prosthesis by seeding autologous venous tissue fragments into its wall. In an animal study, complete endothelialization was observed in the entire inner surface of the prosthesis within 2 weeks after implantation. A piece of peripheral vein was minced with scissors and then stirred into saline to create a tissue suspension. This suspension was enmeshed into the wall of a highly porous fabric vascular prosthesis by repeated pressurized injections with a syringe. The prostheses (7 mm inside diameter and 5.7 cm in length), seeded with tissue fragments, were implanted into the descending thoracic aorta of 25 dogs, and they were removed from 1 hour to 2 months after implantation. Twenty-five prostheses, preclotted with fresh blood, were used as control prostheses. In the seeded graft, a thin fibrin layer covered the inner surface just after implantation, but countless numbers of endothelial cells migrated from the fragments and came up to the luminal surface like multiple "mushrooms" under the fibrin layer. Smooth muscle cells made multiple layers underneath the endothelial cell layer. The healing proceeded equally at every part. By this active migration and proliferation, the inner surface was completely healed within 2 weeks.

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The authors successfully applied a method to accelerate endothelialization by tissue fragmentation to a small diameter fabric vascular prosthesis. Tissue fragment seeded grafts showed rapid healing of the neointima. The thrombogenicity of the collagen fibrils in the fragments, however, caused major problems when the method was applied to small diameter grafts: the positively charged collagen fibrils aggregated the negatively charged platelets. The authors masked the fibrils electrostatically with heparin molecules, which are negatively charged. A canine jugular vein was resected, minced into tissue fragments, and suspended in the heparin solution; it then was sieved through the wall of a fabric prosthesis. The grafts (4 mm internal diameter and 3.5 cm in length) were implanted into both carotid arteries of six dogs (12 grafts). Tissue fragment seeded grafts without heparin also were implanted into six dogs. As a control, preclotted fabric grafts were implanted into six dogs (12 grafts). These grafts occluded within 1 week, whereas all the masked grafts were patent without thrombi. In vitro examination of heparin release revealed that approximately 92% of heparin in the graft was released during the first 5 hr, but approximately 6% remained after 25 hr. These results indicate that the method is applicable to small diameter arterial grafts.

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Microporous prostheses of 1.5 mm internal diameter were fabricated with a polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE)n co-polymer by the spray phase inversion technique. Some of the grafts were made piezoelectric by poling under a high electrical field. Overall, 24 poled grafts (P) and 24 unpoled grafts (UP) (15-22 mm in length) were implanted in the infrarenal aorta of 48 adult rats. Patency rates in P were 100% (8/8) at 2 days, 100% (8/8) at 2 weeks, 75% (6/8) at 6 months, and 92% total (22 of 24). Patency rates in UP were 100% (8/8) at 2 days, 63% (5/8) at 2 weeks, 100% (8/8) at 6 months, and 88% total (21 of 24). Thus there was no significant difference in patency between the two types of grafts. Both showed similar macroscopic and microscopic findings. At 2 days, fibrin deposition was somewhat heavier on the poled grafts, but no difference in surface platelet deposition could be detected. Endothelialization was observed from both anastomoses at 2 weeks and was almost complete at 6 months. The excellent biocompatibility of PVDF-TrFE and the microporous structure of the grafts were probably the dominant factors in success with these grafts. Although piezoelectric activity in excised cleaned poled prostheses remained significantly higher than that in the control UP, the charges developed may have been too small to exert a biologic effect, either because of insufficient dipole orientation or inadequate mechanical deformation.

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