Yoshihiro Wada

Inhibition by Eicosapentaenoic Acid of Oxidized-LDL- and Lysophosphatidylcholine-Induced Human Coronary Artery Smooth Muscle Cell Production of Endothelin

The objectives of the present study were (1) to determine whether oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (lyso-PC), a major phospholipid component of oxidized LDL, stimulate the production of endothelin-1 (ET)-1 in cultured human coronary artery smooth muscle cells (SMCs), and (2) to examine the possible effect of an antiatherogenic agent, eicosapentaenoic acid (EPA), on oxidized-LDL- and lyso-PC-stimulated ET-1 production in these cells. Oxidized LDL (10–50 µg/ml) and lyso-PC (10–7 to 10–5 mol/l) stimulated ET-1 production in a concentration-dependent manner. By contrast, the effects of native LDL and phosphatidylcholine were modest or absent. Lyso-PC (10–7 to 10–5 mol/l) and oxidized LDL (10–50 µg/ml) significantly induced particulate protein kinase C (PKC) activation. Lyso-PC- and oxidized-LDL-stimulated ET-1 production was significantly inhibited by PKC inhibitor, PKC (19–36). EPA (80–160 µmol/l) clearly suppressed ET-1 production stimulated by oxidized LDL and lyso-PC in a concentration-dependent manner. Furthermore, EPA (160 µmol/l) significantly inhibited lyso-PC (10–5 mol/l)- and oxidized LDL (50 µg/ml)-induced particulate PKC activation. Results suggest that oxidized LDL and lyso-PC stimulate ET-1 production by a mechanism involving activation of PKC, and that EPA suppresses ET-1 production stimulated by lyso-PC as well as oxidized LDL probably through the modulation of PKC in human coronary artery SMCs. EPA may exert an antiatherosclerotic effect, in part, through these mechanisms.

Prevention of cerebral thromboembolism by low-dose anticoagulant therapy in atrial fibrillation with mitral regurgitation.

Controversy exists regarding the influence of mitral regurgitation (MR) on thromboembolic risk in patients with atrial fibrillation. We aimed to investigate retrospectively a reduction of risk for stroke due to MR in atrial fibrillation and to evaluate the effectiveness of low-intensity anticoagulation therapy. In 313 patients with atrial fibrillation, transthoracic echocardiography was performed and MR was graded. Between the groups with no or mild MR (n = 209) and with moderate or severe MR (n = 104), age, sex, treatment, history of diabetes, hypertension, hyperlipemia and mitral stenosis, and previous stroke were compared. No significant differences in clinical characteristics, treatment, or history were observed between the two groups. The incidence of thromboembolism was significantly higher in the group with no MR (48 patients [23%]) than in the group with MR (14 patients [13%], p < 0.05). In the MR group, previous stroke was frequently observed in patients without warfarin treatment (11 of 51 patients) compared with patients with low-dose warfarin treatment (international normalized ratio of 1.6–1.8) (3 of 53 patients, p < 0.05). Consequently, the thromboembolic event was markedly prevented by low-dose warfarin treatment.

Contrast transesophageal echocardiography in diagnosing congenital enlargement of the right atrium: A case report

Congenital malformation of the right atrium or the coronary sinus is rare, and cases are clas sified into 1 of the following 4 categories: (1) congenital enlargement of right atrium, (2) single diverticulum, (3) multiple diverticula of the right atrium, and (4) diverticulum of the coronary sinus. This report presents a 63-year-old man with cardiomegaly and no chest symptoms. A chest radiograph revealed an enlarged cardiac silhouette with a prominent right heart border. Although a transesophageal echocardiography revealed marked enlargement of the right atrium, neither further anomaly nor massive regurgitation was observed. The systolic pulmonary artery pressure derived from the peak velocity of mild tricuspid regurgitation was 38 mm Hg. Secondary enlargement of the right atrium due to atrial septal defect or pulmonary venous connection anomaly was deemed negligible by use of transesophageal contrast echocardiography, and primary enlargement of the right atrium was confirmed. Trans esophageal echocardiography using ultrasound contrast was determined to be feasible for diagnosing congenital malformation of the right atrium.

A novel color M-mode Doppler echocardiographic index for left ventricular relaxation: depth of the maximal velocity point of left ventricular inflow in early diastole

Abstract Color M-mode Doppler echocardiography (CMD) has been utilized in assessing left ventricular (LV) filling dynamics. We tested a novel CMD index, the depth of the spatiotemporal maximum of early diastolic inflow (D-maxV) in the left ventricle, to clarify its significance in assessing LV diastolic function. In 26 normal subjects and 32 patients with ischemic heart disease, D-maxV was determined with CMD as the distance from the mitral valve opening point to the center of the aliasing area in early diastole. Transmitral flow velocity was measured with pulsed Doppler. During routine catheterization, high-fidelity LV pressure measurements yielded diastolic variables in patients. D-maxV was significantly lower in the patients than the normals (13.0 ± 7.0 vs 23.4 ± 6.8 mm, P < 0.0001). D-maxV exhibited significant linear correlations with the minimal first derivative of LV pressure (r = 0.72, P < 0.01), the time constant of isovolumic relaxation (r = −0.67, P < 0.01), and LV minimal pressure (r = −0.53, P < 0.02) in the patients with wide ranges of peak early to late inflow velocity ratio (0.43–3.9) and deceleration time of early filling (79–293 ms). D-maxV showed an inverse correlation with LV end-diastolic pressure (r = −0.53, P < 0.02) and no significant correlation with mean pulmonary capillary wedge pressure. Moreover, Kaplan-Meier analysis focusing on the patients with myocardial infarction revealed that the group with D-maxV < 10.4 mm (n = 13) exhibited a lower cumulative cardiac event-free rate than that with D-maxV ≥ 10.4 mm (n = 14) (49.4% vs 92.9% at 5 years, P < 0.05). The depth of the spatiotemporal maximum of early diastolic LV inflow velocity reflects LV relaxation and is free of pseudonormalization. Evaluation of the LV relaxation separately from preload may have a prognostic value for myocardial infarction.

Suppression of Fatty Acid Metabolism After Exercise Stress in Patients with No Electrocardiographic ST Segment Shift During Balloon Angioplasty

Although ST segment shift is a marker of myocardial ischemia, some patients have no ST segment shift during percutaneous transluminal coronary angioplasty (PTCA). The aim of this study is to investigate myocardial perfusion and metabolism in adaptation for ischemia using 201TI and 123I-BMIPP dual exercise stress myocardial single photon emission computed tomog raphy (SPECT) (dual stress SPECT). In 28 patients with coronary artery disease, dual stress SPECT was performed 3 weeks before PTCA. Early and delayed images were obtained at 5 minutes and at 3 hours after termination of ergometer stress, respectively. During PTCA, 12- lead ECG was recorded, and a significant ST segment shift was defined as more than 1 mm elevation or a depression of the J-point at the first ballooning. No collateral circulation on the coronary angiogram or 201TI filling on the delayed images were observed on any of the target regions of PTCA. Patients were divided into 2 groups: with (Group A: n = 15) and without (Group B: n = 13) significant ST segment shift during PTCA. A redistribution of TI was observed in 14 (93%) of Group A and 10 (77%) of Group B patients. Incidence of BMIPP redistribution was significantly higher in Group B (11 [85%]) than in Group A (3 [20%]) (p < 0.05). Redistribution of BMIPP means suppression of fatty acid metabolism during exercise stress. Augmentation of glucose metabolism is speculated to be an energy source in ischemic preconditioning.