Masaki Kajimoto

Basic fibroblast growth factor slow release stent graft for endovascular aortic aneurysm repair: A canine model experiment

OBJECTIVE Persistent endoleak and endotension, complications after endovascular aortic repair, may be caused by an unorganized thrombus inside the aneurysm. The experimental study was designed to evaluate the effectiveness of stent grafts (S/Gs) with slow release of basic fibroblast growth factor (bFGF) for the organization. METHODS The S/Gs were constructed of self-expanding Z stent covered with expanded polytetra fluoroethylene graft, and coated with elastin to be able to bind and slowly release bFGF. Five elastin-coated S/Gs with bFGF (bFGF-S/Gs) and without bFGF (C-S/Gs) were placed in the normal canine aorta respectively. The thoracic aortic aneurysm models were surgically created with a jugular vein patch in 12 beagles. S/Gs with six holes, for creating endoleaks, were used in the experiment of aneurysmal repair. The bFGF-S/Gs (n = 6) and C-S/Gs (n = 6) were implanted. The beagles were sacrificed at two weeks after the endovascular procedure and examined histologically. RESULTS The bFGF-S/Gs induced six times the intimal proliferation of the C-S/Gs in normal aorta. Twelve animals had successfully created aneurysms, and had endoleaks just after the endovascular procedure. At two weeks after the endovascular procedure, the percentage of fibrous area in the aneurysmal cavity treated with bFGF-S/G (35.7 +/- 4.3%) was significantly greater than C-S/G (13.6 +/- 2.2%) (P < .01). CONCLUSION bFGF-S/Gs are effective for accelerating organization of the aneurysm cavity and developing neointima. Further research on bFGF-S/Gs would clarify the association of endoleaks.

Method of cell transplantation promoting the organization of intraarterial thrombus.

Background—Endovascular aortic repairs have been developed as less invasive treatments for aortic aneurysms. Some aneurismal cavities, however, remain without organization, causing a re-expansion of the aneurysms. We studied cell transplantation into the aneurismal sac to promote the organization of thrombus for the complete healing of aneurysms. Methods and Results—Skin fibroblasts and skeletal myoblasts were isolated from rats for cell transplantation. An intraarterial thrombus model was made by ligation of the carotid artery. Culture medium (medium group, n=11), collagen gel (gel group, n=11), fibroblasts with collagen gel (F group, n=15), myoblasts with collagen gel (M group, n=12), or mixture of fibroblasts and myoblasts with collagen gel (F+M group, n=14) were injected into the thrombus. After 28 days, histologically, the arterial lumens of the F and M groups were partly filled with fibrous tissues, whereas in the F+M group organization was almost completed and luminal sizes diminished. Immunohistochemical staining demonstrated that α-smooth muscle actin-positive cells were more abundantly contained in the organized area of the F+M group than in the other groups. We also analyzed cellular function in vitro with immunofluorescence; coculture of fibroblasts and myoblasts showed that the fraction of α-smooth muscle actin-positive fibroblasts increased. This phenomenon accounts for the rapid organization of thrombus in the F+M group in vivo. Conclusions—Cell transplantation accelerated thrombus organization. Especially, myoblasts enhanced differentiation of fibroblasts into myofibroblasts, contributing to rapid thrombus organization. Cell transplantation into unorganized spaces seems applicable to endovascular treatment of aneurysms.

Patch angioplasty and neo-ostium creation for intramural left coronary artery

Anomalous aortic origin of the coronary artery is a rare cardiac anomaly which induces myocardial ischemia and is associated with sudden death. We operated on a 25-year-old female with syncopal episodes who had an intramural left coronary artery. A neo-ostium was created in the left sinus but the initial neo-ostium seemed small because of the hypoplastic intramural segment of the left coronary artery. Therefore, saphenous vein patch angioplasty was added for ostial enlargement. The patient was symptom-free at one year follow-up and exercise stress test was negative for ischemia.

Development of a New Method for Endovascular Aortic Repair Combination Therapy of Cell Transplantation and Stent Grafts With a Drug Delivery System

Background— Endovascular aortic repair by stent grafts (S/Gs) has been developed as a less invasive treatment for aortic aneurysms. However, some aneurysmal cavities can remain without organization, causing re-expansion. We demonstrated previously that transplantation of a cell combination (myoblasts and fibroblasts) promoted thrombus organization in a rat model. We also developed basic fibroblast growth factor (bFGF) slow-delivery S/Gs coated with elastin and impregnated with bFGF. Here, we evaluated the effects of cell transplantation combined with bFGF slow release on canine thoracic aortic aneurysmal sacs after S/Gs repair. Methods and Results— Thoracic aortic aneurysms were surgically created with jugular vein patches in 15 beagles. Myoblasts and fibroblasts of autologous skeletal muscle were isolated and cultured for cell transplantation. The S/Gs had 6 holes and produced endoleaks in the excluded cavities. Collagen gel (gel group, n=5) or a mixture of skeletal myoblasts and fibroblasts with collagen gel (cell group, n=5) were injected into the aneurysmal sacs excluded by the S/Gs. We also studied the effects of combined therapy of bFGF slow-release S/Gs and cell transplantation (hybrid group, n=5). After 14 days, histological analyses revealed that the excluded aneurysmal cavities of the gel group were filled with fresh thrombus, whereas the excluded cavities in the cell-transplanted groups were occupied by organized tissue. The percentages of the organized areas relative to the excluded cavities, evaluated by Massons trichrome staining, were 18.1±4.0%, 52.6±4.0%, and 77.1±6.9% in the gel, cell, and hybrid groups, respectively. Collagen fibers had already appeared, and increased numbers of &agr;-smooth muscle actin–positive cells were observed in the hybrid group. Conclusions— Cell transplantation accelerated thrombus organization. Moreover, slow release of bFGF enhanced the effects of cell transplantation. Cell transplantation into unorganized spaces may improve the outcomes of endovascular treatments of aortic aneurysms.

Congenital pulmonary vein stenosis with anomalous pulmonary venous connection.

An 11-month-old boy with congenital pulmonary vein stenosis, partial anomalous pulmonary venous connection, and ventricular septal defect is described. Angiocardiography demonstrated stenosis between the right upper pulmonary vein and high superior vena cava and obstruction of the right lower pulmonary vein. For pulmonary vein stenosis, we performed transverse sutured plasty for the right upper pulmonary vein, followed by right lower lobectomy. In some patients, combined management for pulmonary vein stenosis is effective.