Fumihiko Hara

Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.

BACKGROUND Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. METHODSANDRESULTS Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated β-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs. CONCLUSIONS H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).

Assessment of left ventricular diastolic function using color kinesis: differentiation between normal and pseudonormalized patterns

PurposeDoppler examination of transmitral flow has been widely used to noninvasively assess left ventricular (LV) diastolic function. However, it has been demonstrated that transmitral flow velocity is dependent on LV relaxation and left atrial pressure. Increases in left atrial pressure compensate for the effects of impaired LV relaxation, frequently resulting in a “pseudonormalization” of the transmitral flow pattern. The purpose of this study was to assess whether analysis of diastolic color kinesis (CK) can be applied to differentiation between normal and pseudonormalized (PN) patterns of LV inflow.MethodsWe studied 60 subjects with a ratio of early to late transmitral peak velocities (E/A) greater than 1.0 according to conventional Doppler echocardiography. All subjects simultaneously underwent measurement of the early diastolic mitral annular velocity (e′), which was measured by tissue Doppler imaging, and LV ejection fraction (EF), which was calculated by the modified Simpson method. Study subjects were classified into the following three groups according to the value of e′ and EF: (1) the normal group (e′ > 10 cm/s, EF > 60%), including 20 subjects (mean age 35 ± 10 years); (2) the PN1 group (e′ < 7 cm/s, EF > 50%), consisting of 20 patients [mean age 63 ± 11 years, 15 patients with hypertensive heart disease (HHD), 5 patients with aortic valve stenosis]; and (3) the PN2 group (e′ < 7 cm/s, EF < 50%), consisting of 20 patients (mean age 61 ± 17 years, 18 patients with dilated cardiomyopathy, 2 patients with HHD). Diastolic CK images were obtained for each subject from the LV midpapillary short-axis view. Analysis of CK diastolic images was performed using ICK software. The CK-diastolic index (CK-DI) was defined as the calculated LV segmental filling fraction during the first 30% of diastole, expressed as a percentage. The mean CK-DI was determined from the average CK-DI of six LV segments.ResultsThe mean CK-DI was 70.9% ± 6.5% in the normal group, 46.3% ± 10.4% in the PN1 group, and 36.3% ± 5.1% in the PN2 group. The mean CK-DI was significantly reduced in the PN1 and PN2 groups compared with the normal group (P < 0.0001). Although there was no difference in e′ (PN1 group: 4.6 ± 1.8 cm/s, PN2 group: 4.4 ± 1.7 cm/s) between the two pseudonormalized patient groups, the mean CK-DI was significantly reduced in the PN2 group compared with the PN1 group (P < 0.005). The reduction in mean CK-DI was seen not only in pseudonormalized patients with LV systolic dysfunction but also in those with preserved LV systolic function.ConclusionThe analysis of diastolic CK with ICK software is a useful method for detecting delayed early diastolic relaxation. We concluded that diastolic CK images may be applied to differentiating between normal and pseudonormalized patterns of LV inflow.

Transcatheter atrial septal defect closure in a patient with paradoxical brain emboli: who should treat it and who should be treated?

This report presents the case of a 51-year-old female who was admitted to a local hospital because of a persistent headache. A diagnosis of multiple cerebral infarctions was thereafter made, but there was no evidence of either atherosclerosis or atrial fibrillation. The case was thought to be a cryptogenic stroke, however, Doppler ultrasonography of the lower extremities showed venous insufficiency. Transesophageal echocardiography revealed a secundum atrial septal defect (ASD) with a left to right shunt. Therefore, the final diagnosis was paradoxical brain emboli, and transcatheter ASD closure was successfully performed by cardiologists without any sequelae.

Comparison of Direct Oral Anticoagulants and Warfarin in the Treatment of Deep Venous Thrombosis in the Chronic Phase: A Large, Single-Center, Observational Study

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.