Akira Kusaba

Radical open endvenectomy with autologous pericardial patch graft for correction of Budd-Chiari syndrome.

A surgical technique for the treatment of Budd-Chiari syndrome associated with vena caval obstruction has been devised. The occluded hepatic vena cava and hepatic veins were reconstructed by open endvenectomy, using an autologous pericardial patch graft and a femorofemoral bypass technique. The hepatic artery and portal vein were not controlled with vascular clamps during the surgery. Between 1979 and 1994, 29 patients were treated using this technique and achieved good results. All the patients did well with good function of the reconstructed vena cava and of the hepatic veins, and showed acceptable reduction of symptoms caused by portal hypertension and caval stagnation.

Lymphatic vessel-to-isolated-vein anastomosis for secondary lymphedema in a canine model.

To design a more rational and effective surgical method of performing lymphatic-venous anastomosis to treat secondary lymphedema of the lower extremities, the following experiments were conducted on three groups of dogs: group A underwent an end-to-side lymphatic node-to-vein anastomosis at the inferior vena cava; group B underwent a “burying” lymphatic vessel-to-vein anastomosis at the femoral vein; and group C underwent a burying lymphatic vessel-to-isolated-vein anastomosis at the femoral vein. In group C, the femoral venous segment was isolated by distal ligation and proximal valvuloplasty and the patency of the anastomosis was investigated by infusing yellow Microfils through the distal lymphatic vessel. The patency of the anastomosis was nil in group A by 10 days after the anastomosis, 40% in group B by 180 days; and 71.4% in group C by 180 days, respectively. Thus, we clinically applied the technique of lymphatic vessel-to-isolated-saphenous-vein anastomosis in a patient with secondary lymphedema of the bilateral lower extremities. A satisfactory reduction in the size of the limbs was achieved and there has been no further recurrence of cellulitis in the 42 months since her surgery. This study shows that lymphatic vessel-to-vein anastomosis is an effective technique for the surgical management of secondary lymphedema, so long as the anastomosis is completely protected from any contact with blood.

Microscopic and immunohistological studies on intimal hyperplasia of the arterially implanted autovein graft and its anastomosis in dogs

The fate of intimal hyperplasia of arterially implanted autovein bypass grafts and their distal end-to-side ananstomoses in dogs was studied microscopically and immunohistologically. The bypass grafting was done under conditions of abnormal blood flow and high peripheral resistance. Intimal hyperplasia of the graft first became evident 7 days after implantation and the thickness increased to about 500 μm 3 months or more after the implantation. The intimal hyperplasia was related to an active proliferation of smooth muscle cells which proved positive for alpha-smooth muscle actin staining. Moreover, it was more dominant at the toe and heel of the anastomosis and moderately apparent on the floor of the host artery. The constituent elements of the hyperplastic intima at the anastomosis were fibroblast-like cells and extracellular collagen fibers which were negative for alpha smooth muscle actin staining. This study revealed that the features of intimal hyperplasia at the distal anastomosis in autovein bypass grafting differed from those of the implanted autovein graft itself; the former being related to excessive proliferation of fibroblasts and collagen fibers while the latter displayed an active proliferation of smooth muscle cells.

Clinical studies on the vasodilating and anti-platelet effects of OP-41483, a prostacyclin derivative

The vasodilating and anti-platelet actions of OP-41483 was studied to determine the effective dose of this drug for the treatment of ischemic lower limbs. The compound was given to 11 patients intravenously at rates of 2.5, 5.0 and 10.0 ng/kg/min. Infusion at a rate of 10 ng/kg/min increased the mean flow rate of the tibial arteries from 3.15±1.77 ml/min before the infusion, to 7.89±2.51 ml/min (p<0.001) and to 6.38±3.19 ml/min (p<0.001), at the time of, and 60 minutes after the cessation of the infusion, respectively. The peripheral flow resistance of the tibial arteries was reduced from 2.1±1.12×105 dyne·sec/cm5 before the infusion to 0.9 ±0.33×105 dyne·sec/cm5 (p<0.001) and to 1.2±0.78×105 dyne·sec/cm5 (p<0.05), at the time of, and 60 minutes after the cessation of the infusion. ADP-induced platelet aggregation was reduced from 73.3±17.6% before the infusion to 50.7±24.5% (p<0.01) and to 64.0±23.5% (p<0.05), at the time of, and 60 minutes after the cessation of the infusion, respectively. Collageninduced platelet aggregation was also reduced from 71.4±24.0% to 66.6±21.5% before and after the infusion (p<0.05).

Distribution and localization of cells and collagens in the proliferated intima of arterially implanted autovein grafts

We examined the microscopic features and distribution of collagens in the hyperplastic intima of arterially implanted autovein bypass grafts under conditions of a reduced blood flow with a poor distal outflow. Vascular anastomosis was made using 7–0 nonabsorbable polypropylene sutures (PP group), or absorbable polydioxanone sutures (PDS group). On the contralateral limb, an autovein bypass graft was performed under normal flow conditions (NF group). The thickness of the intima in the NF group was approximately 50μm throughout the duration of the study, while in the PP and PDS groups, intimal hyperplasia progressed to 290±112μm and 267±123 μm, respectively, at 13 months after grafting. Collagen accumulated significantly in both the PP and PDS groups; types IV and V collagen in particular increased considerably in the deep layer. Regardless of the suture materials, the progression of intimal hyperplasia was considered to be closely related to the poor distal outflow to be and caused by the proliferation of myofibroblasts and active production of collagen. The increase in types IV and V collagen, particularly in the deep layer of the hyperplastic intima, was due to development of numerous vasa vasora in this region.

Pathophysiological features of intimal hyperplasia of the arterially implanted autovein graft and its anastomosis in dogs

We investigated pathophysiological features of intimal hyperplasia of arterially implanted autovein graft and its distal end-to-side anastomosis under conditions of poor distal runoff. Intimal hyperplasia of the graft was significantly evident, became 70.5±38.5 µm thick at 14 days with infiltration of myofibroblasts, and increased to 420±199.7 µm at 6 months. The proliferated neointima was strongly positive for alpha-smooth muscle (A-sm) actin staining. Cells in the entire layer of the graft were diffusely labeled with BrdU at 14 days. At 3–6 months after grafting, cells in the superficial layer of the neointima were scarcely labeled with BrdU, however, cells in the deeper layer were strongly labeled. At the distal end-to-side anastomosis, mural thrombi deposited on the suture line were replaced by fibrous tissues with infiltration of fibroblast-like cells within 14 days, and proliferated considerably at 3–6 months. The neointima at the toe portion was thickened to 82.5±50.7 µm at 14 days and increased to 370.6±40.0 µm at 6 months. The superficial layer of the proliferated neointima consisted of mature smooth muscle cells positive for A-sm actin staining and scarcely labeled with BrdU. However, the deeper layer was negative for A-sm actin staining and strongly labeled with BrdU. In conclusion, intimal hyperplasia is caused by infiltration of myofibroblasts in the graft and of fibroblast-like cells at the anastomosis. Proliferation of these cells is progressive at the deeper layer of the neointima, even at 6 months after grafting.

Development of Luminally Originating Vasa Vasorum in Arterially Implanted Autogenous Vein Graft and Related Anastomosis in Dogs

Using light and scanning electron microscopes, the authors examined the development of luminally originating vasa vasorum in the course of intimal hyperplasia of vein grafts implanted to the canine femoral artery under conditions of abnormal blood flow with a high peripheral resistance. Five days after the implantation, the luminally originating vasa vasorum in the autogenous vein grafts developed dominantly near the anastomosis and often at the site of the area of valvular sinus. This vasa vasorum took the form of numerous small holes on the luminal surface of the graft and along the suture materials at the site of the anastomosis. These holes were lined with endothelial-like cells two weeks after the implantation, and four weeks later these cells were distributed in the thickened neointima connecting the vasa vasorum in the media and adventitia. This vasa vasorum observed on the thickened neointima at the area of the valvular sinus of the vein graft at more than five days after the implantation was considered to have developed in the course of organization of the mural thrombi deposited on the suture line at and on the area of the valvular sinus. Thus, numerous interstices of the vessel wall, formed along the suture materials at the anastomosis, and some clefts, formed with shrinkage of the deposited mural thrombi at the area of the valvular sinus, are the source of the luminally originating vasa vasorum.

Tissue and cellular distribution of alpha-L-iduronidase in the pig.

We investigated the alpha-L-iduronidase activity of various pig tissues. Furthermore, we examined the tissues using antibody, enzyme immunoassay (EIA), and immunohistochemical methods. The amounts of enzyme measured by the EIA method in the various tissues were proportional to their enzyme activities and also to their immunohistochemical characteristics. The tissues could thus be classified into three groups: a high enzyme activity group composed of the liver, kidney, and spleen; a moderate activity group comprising the lung, lymph nodes, stomach, ileum, colon, and pancreas; and a low activity group consisting of the heart, diaphragm, iliopsoas muscle, cerebrum, cerebellum, and skin. The molecular weight of the enzyme in each tissue did not reveal any heterogeneity, having two components of 70 KD and 62 KD by Western blot analysis. Immunohistochemically, alpha-L-iduronidase was strongly detected in the lysosomal membranes of cells of the mononuclear phagocyte system, epithelial cells of the proximal tubules in the kidney, and some blastic cells, whereas hepatocytes revealed weak positive reactions. The tissue and cellular distribution of the enzyme appeared to have a close relation to tissues that manifest or are affected by alpha-L-iduronidase deficiency.

Idiopathic arterial calcification in 9-year-old boy: a successful reconstruction for ilio-femoral occlusion

We treated a 9-year-old boy suffering from underdevelopment of the length as well as circumference of the left lower extremity due to idiopathic arterial calcification of the left ilio-femoral artery. There was no deposition of calcium on the other arteries and tissues of the body. He had undergone aorto-internal iliac bypass graft with resection of the calcific iliac and superficial femoral arteries in the National Fukuoka Central Hospital when he was 4 years old, but the graft became occluded. He was admitted to the University of the Ryukyus Hospital. The common femoral artery was completely occluded with severe deposition of calcium on the wall and with gritty contents. The profunda femoris artery and the proximal part of the superficial femoral artery were also completely occluded with organized thrombi. Re-establishment of blood flow to the ischemic left lower extremity was performed with an ilio-femoral cross-over synthetic bypass and femoro-popliteal saphenous vein bypass graft,in situ. The patient has been well with adequate pulses of the pedal and posterior tibial artery 8 months after surgery.