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Norihide Fukushima

Publications and source records attributed to Norihide Fukushima.

32 records · Page 2Linked to original sources
PubMed2004

Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats.

OBJECTIVE: Hepatocyte growth factor (HGF) is a multi-potent growth factor, which has anti-fibrotic effects for lung injuries. In this study, we investigated whether human HGF gene transfer may attenuate the medial hypertrophy of pulmonary arteries and enhance the ameliorating effect of prostacyclin in monocrotaline (MCT)-induced pulmonary hypertension in rats. METHODS AND RESULTS: The day before MCT injection, HVJ-liposome complex with the cDNA encoding HGF gene (H group), PGIS gene (P group), and both HGF and PGIS gene (HP group) were transfected to the liver of rats as drug delivery system for the lung. Rats transfected with control vector served as controls (C group). Twenty-eight days after MCT injection, histological examination showed marked thickening of medial wall of pulmonary arteries and right ventricular hypertrophy. Percent medial wall thickness (%WT) of peripheral pulmonary arteries, pressure ratio of the right ventricle (RV) to the left ventricle (LV), and weight ratio of the RV to the LV plus septum were significantly increased in the control. Percent medial wall thickness was significantly ameliorated in H group and HP group in comparison with C group. Pressure and weight ratio of RV to LV was significantly ameliorated in P group and HP group in comparison with C group, and was significantly ameliorated in HP group than P group. CONCLUSIONS: In vivo gene transfection with HGF gene attenuated the medial hypertrophy of pulmonary arteries and enhanced the ameliorating effect of prostacyclin for pulmonary hypertension in MCT rats. Thus, gene therapy with HGF and PGIS may be a promising strategy for severe pulmonary hypertension.

Animals↗
PubMed2004

Early result of heart transplantation in Japan: Osaka University experience.

Since the new organ transplantation law was established in 1997, 17 heart transplantations have been performed in Japan, 7 of which were carried out at Osaka University Hospital. Recipient diagnosis was dilated cardiomyopathy in 2, dilated phase of hypertrophic cardiomyopathy in 4, and post-myocarditis cardiomyopathy in 1. Ages ranged from 8 to 49 years with a mean of 35.3 years. Five patients were bridged with a left ventricular assist device. The waiting period was 182-977 days (mean, 643 days). There was no early or late death during follow-up of 1-4.8 years. Under a standard triple-drug regimen using mycophenolate, there were 3 rejection episodes greater than grade 3 in 2 patients, and humoral rejection requiring plasmapheresis in one. A young boy whose donor was a hemodynamically compromised adult developed neurological sequelae after resuscitation following ventricular tachycardia. All patients were discharged and went back to work or their regular daily life. Although the donor shortage is still severe in Japan, the resumption of heart transplantation has been satisfactory, and left ventricular assist devices have played a crucial role.

Adult↗
PubMed2004

Arrhythmias late after repair of tetralogy of fallot: a Japanese Multicenter Study.

BACKGROUND: Arrhythmia is a major late complication in adults with repaired tetralogy of Fallot, although a large-scale study has not been carried out in Japan. METHODS AND RESULTS: A nationwide multicenter study with 512 operative survivors was performed. Actuarial survival rate at 30 years (maximum follow-up) was 98.4%. Fifty-four patients (10.5%) had clinically important arrhythmias, including 23 patients with bradycardia caused by sick sinus syndrome or atrioventricular block (AVB). A patient with complete AVB (CAVB) without pacemaker implantation (PMI) died later. Two patients had sustained ventricular tachycardia (VT) and syncope was reported in 18 patients with ventricular arrhythmias (VA). Atrial tachyarrhythmias were observed in 13 patients. Older age at operation was a risk factor for atrial fibrillation/flutter, longer postoperative survival duration for VA, and QRS duration >120 ms for VT. Perimembranous ventricular septal defect was related to CAVB. Right ventricular outflow patch was not a risk factor. Importantly, 60% of the subjects had QRS duration <120 ms. CONCLUSION: The prevalence of serious arrhythmias is low in Japanese TOF patients as compared with the results from Western countries. CAVB without PMI and VT are the major risk factors for late morbidity and mortality. The excellent result could be related to the narrow QRS after surgery.

Adolescent↗
PubMed2004

Valvuloplasty for anterior mitral leaflet prolapse due to infective endocarditis: report of 2 cases.

We report 2 clinical cases of successful repair of an infected mitral valve with a broad-range prolapse of the anterior mitral leaflet (AML) with large vegetation. The chordal transfer technique was used in both cases, and autologous pericardium was transplanted in one case. There was neither residual mitral regurgitation nor recurrence of mitral valve infection. Chordal transfer is a useful technique for AML lesions of infective endocarditis if the corresponding area of the posterior ML remains normal, and even in the case of a broadly destroyed lesion of the AML, it is valuable to try to apply this technique with an autologous pericardial patch.

Adult↗
PubMed2003

The clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery.

BACKGROUND: Minimally invasive cardiac surgery is now becoming standard in the correction of simple congenital cardiac malfbrmations. We introduced a clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery, and assessed the function of the pathway in children with atrial or ventricular septal defects, comparing minimally invasive surgery to repair through a conventional full sternotomy. METHODS: We studied 15 children of school age who underwent repair of an atrial or ventricular septal defect through a lower midline sternotomy, and 10 children undergoing repair through a full sternotomy. The clinical pathway was for extubation to take place in the operating room, echocardiographic evaluation on the 5th postoperative day, and discharge home on the 7th postoperative day, with return to school within 2 weeks, and resumption of all gymnastic activity within 6 weeks of the minimally invasive surgery. RESULTS: In those having a lower midline sternotomy, postoperative hospital stay was 7.4 +/- 0.8 days, with return to school 8.0 +/- 2.4 days after discharge. They resumed gymnastics 41 +/- 11 days after the minimally invasive surgery. In those having a full sternotomy, in contrast, these parameters were 13.5 +/- 2.7, 23.1 +/- 8.4, and 95 +/- 43 days, respectively. Of the 15 children undergoing a minimally invasive approach, 12 (80%) fulfilled the criterions of our clinical pathway. CONCLUSIONS: We conclude that minimally invasive cardiac surgery can safely be performed in children. In addition to its cosmetic role, the technique has added value in promoting early return to normal school life, including gymnastics.

Adolescent↗
PubMed2003

[Heart transplantation in Japan].

Since February 1999, organ transplantation from a brain-dead donor has been started in Japan. For more than 3 years, 91 patients underwent organ transplantation from 22 donors. Until November 2002, 132 patients have been registered to Japan Organ Transplant Network as a heart transplant candidate and 16 and 9 underwent heart transplantation (HTx) in Japan and abroad, respectively, while 37 died during waiting. 11 of 16 HTx recipients were implanted with left ventricular assist device (LVAS: Novacor in 2, TCI-IP in 2 and NCVC in 7). all 16 HTx recipients survived until now. 4 had several rejection episodes which were treated successfully. 5 had infection episodes (pneumonia in 3 and CMV infection in 2). 13 were already discharged and 9 returned to work.

Adolescent↗
PubMed2003

Hypertrophic non-obstructive cardiomyopathy with aortic and mitral regurgitation: an unusual presentation for surgical option.

The case is described of a pediatric patient with hypertrophic non-obstructive cardiomyopathy (HNCM) presenting with aortic and mitral regurgitation. This 17-year-old boy had been followed for HNCM since he was aged 4 years. Serial echocardiography had been showing the emergence and progression of aortic regurgitation and mitral regurgitation since the patient was aged 6 years. He started to have syncope attacks at 16 years of age and fell into congestive heart failure at 17 years. He underwent successful mitral valve repair by means of double-orifice technique, and aortic valve repair with raphe triangular resection, cusp plication and subvalvular annuloplasty.

Adolescent↗
PubMed2002

Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation.

BACKGROUND: In the condition of preexisting vital organ failure induced by heart failure, hepatic failure often progresses despite establishment of adequate hemodynamic support through a left ventricular assist device (LVAD) and results in a high mortality rate. We hypothesized that inflammatory responses, including those induced by infection and their influence on organ perfusion, may contribute to the pathogenesis of this progressive hepatic failure and subsequent multiple organ failure as reported in the current investigation on multiple organ failure after major surgery or trauma. METHODS: Hepatic function and its relation to inflammatory response and hepatic microcirculation were evaluated in 16 consecutive patients who received an implantation of LVAD for end-stage cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5 patients who died from multiple organ failure after severe hepatic failure (group 1) and 11 patients who did not develop severe hepatic failure (group 2). Serum levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator of hepatic sinusoidal function, were measured pre- and postoperatively in both groups. RESULTS: Serum ALT and AST levels during LVAD support were similar in the two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and during the first 20 days of LVAD support were significantly higher in group 1 than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as cholestasis and fibrosis. CONCLUSIONS: Patients with hyperbilirubinemia and inflammatory reactions before LVAD support showed increased hyperbilirubinemia and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics achieved under LVAD support. These results suggest that inflammatory response contributes to subsequent aggravation of hepatic dysfunction, probably with underlying and continuing derangement in hepatic sinusoidal microcirculation even under systemic circulatory support.

Adult↗
PubMed2002

Selective chemokine and receptor gene expressions in allografts that develop transplant vasculopathy.

BACKGROUND: Chemokine systems probably play a role in transplant vasculopathy; however, a comprehensive study of the expression of chemokines and their receptors in this disease has not been performed. METHODS: The expression of all the rat chemokines and chemokine receptor genes for which the nucleotide sequences are known were quantitatively monitored using the fluorescence-based real-time reverse-transcriptase polymerase chain reaction technique, and selected cytokine-receptor pairs were determined using immunohistochemical staining. The analysis covered the whole time course of transplant vasculopathy in 2 different graft models (cardiac and aortic grafts) with 4 different strain combinations of rats. RESULTS: Among the 13 receptor genes examined, the CXCR3, CCR5, and CCR2 genes and those of their corresponding ligands were selectively and strongly induced in grafts that develop transplant vasculopathy. The expression patterns of the receptors were similar in both cardiac and aortic allografts, although their induction and their absolute levels of expression were amplified several fold in the grafted aorta compared with heart grafts. The genes were induced before morphologic changes became apparent and expression was sustained during the whole period of neointimal formation. Interestingly, immunohistochemical staining for CXCR3 showed a unique pattern of expression: we found weak expression on cells in the outer layer of the neointima and adventitia and found the strongest staining in the innermost layer of the neointima. CONCLUSIONS: This study suggested diagnostic as well as potential functional roles of the chemokine-receptor pairs IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2 in rat models of transplant vasculopathy.

Animals↗
PubMed2002

Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats.

BACKGROUND: As one of the future strategies of advanced pulmonary hypertension, intrinsic prostacyclin drug delivery using gene therapy may be useful. We investigated whether transfer of the prostacyclin synthase gene into the liver could ameliorate monocrotaline-induced pulmonary hypertension in rats. METHODS: The human prostacyclin synthase gene was transfected into the liver of rats with monocrotaline-induced pulmonary hypertension. Hemodynamic indices, blood samples, lung tissues, and survival curves were evaluated between rats receiving the gene and control rats. RESULTS: High levels of prostacyclin synthase gene expression were found in the hepatocytes of the prostacyclin synthase group. The level of 6-keto-prostaglandin F(1alpha) was significantly higher in the prostacyclin synthase group (prostacyclin synthase, 35.4 +/- 4.4 ng/mL; control, 22.3 +/- 3.3 ng/mL; P =.0436). The right ventricular/femoral artery pressure ratio was significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 0.60 +/- 0.039; control, 0.88 +/- 0.051; P =.0036). The endothelin-1 levels in the lung tissues were significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 10.42 +/- 2.01 pg/mg protein; control, 19.94 +/- 2.82 pg/mg protein; P =.0176). The survival ratio was significantly higher in the prostacyclin synthase group than the control group (P =.0375). CONCLUSION: This drug delivery system using gene transfer can be considered as an alternative for continuous intravenous prostacyclin infusion for pulmonary hypertension.

Animals↗
PubMed2002

[Heart transplantation].

Since February 1999, organ transplantation from brain-dead donors has started in Japan. During the more than 3 years since, 77 patients have received organ transplantations from 19 donors (heart in 13, lung in 10, liver in 17, pancreas-kidney in 6, pancreas alone in 1, small intestine in 1, and kidney in 29). As of April 2002, 116 patients were registered with the Japan Organ Transplant Network as heart transplant (HTx) candidates, and 13 and 8 underwent HTx in Japan and abroad, respectively, while 32 died while on the waiting list. Ten of 13 HTx recipients were implanted with a left ventricular assist device (LVAS; Novacor in 2, TCI-IP in 1, and NCVC in 7). All 13 HTx recipients were alive at the time of writing. Two had several rejection episodes that were treated successfully. Three had infection episodes (pneumonia in 2 and CMV gastritis in 1). Eleven had been released from hospital, and 8 had returned to work.

Adolescent↗