Kenji Kishida

Implantation of Mesenchymal Stem Cells Overexpressing Endothelial Nitric Oxide Synthase Improves Right Ventricular Impairments Caused by Pulmonary Hypertension

Background— Pulmonary hypertension (PH) is a life-threatening disease. Bone marrow cell transplantation is reported to reduce the development of PH by increasing vascular beds in pulmonary circulation. However, adenoviral overexpression of endothelial nitric oxide synthase (eNOS) in the lung is also known to reduce PH. Because mesenchymal stem cells (MSCs) are potential cell sources for neovascularization, the implantation of MSCs overexpressing eNOS (MSCs/eNOS) may further improve the surgical results. We evaluated the efficacy of MSCs/eNOS implantation in monocrotaline (MCT)-induced PH rats. Methods and Results— MSCs were isolated from rat bone marrow. PH was induced in rats by subcutaneous injection of MCT. One week after MCT administration, the rats received 3 different treatments: MSCs (MSC group), MSCs/eNOS (MSC/eNOS group), or nontreatment (PH group). As the negative control, rats received saline instead of MCT (control group). Right ventricular (RV) hypertrophy and the elevation of RV systolic pressure (RVSP) were evaluated 3 weeks after MCT administration. Moreover, the effects of MSCs/eNOS on survival were investigated in PH induced by MCT 3 weeks earlier. RVSP in both the MSC and MSC/eNOS groups was significantly lower than the PH group. RVSP in the MSC/eNOS group was significantly lower than the MSC group. The RV weight to body weight ratio was significantly lower in the MSC and MSC/eNOS groups than the PH group. The survival time of rats receiving MSCs/eNOS was significantly longer than the nontreatment rats. Conclusion— Intravenous implantation of MSCs/eNOS may offer ameliorating effects on PH-related RV impairment and survival time.

CORONARY RISK FACTORS IN ACUTE KAWASAKI DISEASE : CORRELATION OF SERUM IMMUNOGLOBULIN LEVELS WITH CORONARY COMPLICATIONS

Abstract Background To determine the usefulness of the IgG z‐score (age and sex‐standardized serum IgG level) before intravenous gamma globulin therapy (1VGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD).

Synthetic vascular prosthesis impregnated with mesenchymal stem cells overexpressing endothelial nitric oxide synthase.

Background— Endothelial dysfunction is known to exaggerate coronary artery disease, sometimes leading to irreversible myocardial damage. In such cases, repetitive coronary revascularization including coronary artery bypass grafting is needed, which may cause a shortage of graft conduits. On the other hand, endothelial nitric oxide synthase (eNOS) is an attractive target of cardiovascular gene therapy. The vascular prostheses, of which the inner surfaces are covered with mesenchymal stem cells (MSCs) overexpressing eNOS, are expected to offer feasible effects of NO and angiogenic effects of MSCs on the native coronary arterial beds, as well as improvement of self-patency. Herein, we attempted to develop small caliber vascular prostheses generating the bioactive proteins. Also, we attempted to transduce eNOS cDNA into MSCs. Methods and Results— The MSCs were isolated from rat bone marrow and transduced with each adenovirus harboring rat eNOS cDNA and &bgr;-galactosidase (&bgr;-gal) (eNOS/MSCs and &bgr;-gal/MSCs). The &bgr;-gal/MSCs were impregnated into vascular prostheses, then the expressions of &bgr;-gal on the inner surfaces of them were evaluated by 5-bromo-4-chloro-3-indolyl &bgr;-d-galactoside staining. The NOS activity of eNOS/MSCs was assayed by monitoring the conversion of 3H-arginine to 3H-citrulline. The inner surfaces of the vascular prostheses were covered with MSCs expressing &bgr;-gal. The amount of the 3H-citrulline increased, and eNOS/MSCs were determined to generate enzymatic activity of eNOS. This activity was completely inhibited by NG-nitro-l-arginine methyl ester. Conclusions— The inner surface of expanded polytetrafluoroethylene vascular prostheses seeded with lacZ gene-transduced MSCs exhibited recombinant proteins. Development of eNOS/MSC-seeded vascular prostheses would promise much longer graft patency and vasculoprotective effects.

Quantitative analysis of systolic blood pressure tracking during childhood and adolescence using a tracking index: the Shimane Heart Study.

We used a tracking index to carry out a quantitative analysis of blood pressure tracking in children and adolescents. The index was calculated according to changes in blood pressure quintiles for the whole population during the observation period. The study population consisted of 463 Japanese children living in Izumo, who were examined every 3 years from 6 to 12 years of age in cohort 1, and from 9 to 15 years of age in cohort 2. In both sexes, the tracking index decreased transiently during the period from 9 to 12 years of age and increased again thereafter. The index was higher in girls than in boys except for the period from 12 to 15 years. Correlation coefficients between blood pressure at the first and that at the second examination increased with age in both sexes. We conclude that the tracking index could quantify the degree of tracking. Systolic blood pressure tracked well during childhood and adolescence, and the degree of tracking increased after the age of 12 years in both sexes

Changes of Left Ventricular Isovolumic Relazation Time with Growth in Children

We investigated the changes of left ventricular isovolumic relazation time (LVIRT) with growth and the factors influencing them during childhood, in a 10‐year follow‐up stury.We measured the body height(BH), body weight (BW), lean body weight (LBW), heart rate (HR), Blood pressure (BP), left ventricular muscle volume index (LVMVI), and LVIRT corrected by the preceding R‐R interval) IRT/R‐R), of 187 healthy children at 3‐year intervals (6,9,12,15 years old). IRT/R‐R were prolonged with growth in boys and girls. At the ages of 12 and 15, the IRT/R‐R of girls were longer than those of boys. Significant correlation coefficients for IRT/R‐R on systolic and diastolic, BW and LVMVI were 0.28, 0.31, 0.20, 0.28, respectively. These data suggest that(1)IRT/R‐R is mainly determined by the diastolic BP,(2) left ventricular diastolic function of children develops with growth of body size, especially BW, and(3) left ventricular early diastolic function in adolescents isrelated to sexual maturation.

Relation between Blood Pressure, Left Ventricular Mass and Pulsed Doppler Parameters in Healthy School Children

We analyzed the relations between blood pressure in sitting and supine positions, left ventricular mass (LVM) and Doppler aortic, pulmonary and mitral flow velocity measurements in 163 healthy school children. Systolic blood pressure in a supine position correlated significantly with aortic acceleration (ATc) and ejection time)ETc), corrected by the square of R‐R interval, pulmonary AT and peak flow velocities. Moreover, the systolic blood pressure in a sitting position correlated with pulmonary AT and LVM. LMV correlated with pulmonary ATc, the ratio of AT to ET andaverage acceleration, and aortic ETc and peak flow velocity. These data suggest the following: (1) the posture influences the relation between blood pressure and flow velocity, (2) pulmonary hemodynamics are influenced by systemic blood pressure in healthy children and (3) the development of LVM may be dependentnot only on blood pressure but also on cardiac work in childhood.

Chronic α1 blockade in a patient with Eisenmenger syndromeblockade in a patient with Eisenmenger syndrome

SummaryIn an 18-year-old male with Eisenmenger syndrome cyanosis and erythrocytosis were increasing. The erythrocytosis diminished following oral bunazosin and phlebotomy was not needed during the treatment. When bunazosin was stopped, the erythrocytosis increased, but when it was resumed, the erythrocytosis and general fatigue diminished.