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Naoyuki Hasebe

Publications and source records attributed to Naoyuki Hasebe.

At least 19 recordsLinked to original sources
PubMed2006

Magnesium attenuates isoproterenol-induced acute cardiac dysfunction and beta-adrenergic desensitization.

Sympathetic nervous activation is a crucial compensatory mechanism in heart failure. However, excess catecholamine may induce cardiac dysfunction and beta-adrenergic desensitization. Although magnesium is known to be a cardioprotective agent, its beneficial effects on acute cardiac dysfunction remain to be elucidated. We examined the effects of magnesium on left ventricular (LV) dysfunction induced by a large dose of isoproterenol in dogs. Sixteen anesthetized dogs underwent a continuous infusion of isoproterenol (1 micro g.kg(-1).min(-1)) with or without a magnesium infusion (1 mg.kg(-1).min(-1)). The dose response to small doses of isoproterenol (0.025-0.2 micro g.kg(-1).min(-1)) was tested hourly. A large dose of isoproterenol decreased LV systolic function, increased the time constant of LV isovolumic relaxation, and suppressed the dose response to small doses of isoproterenol in a time-dependent manner. Magnesium significantly attenuated isoproterenol-induced LV systolic and diastolic dysfunction and preserved the dose response to isoproterenol. Serum-ionized calcium significantly decreased with a large dose of isoproterenol but was fully maintained at baseline level with magnesium. A large dose of isoproterenol increased serum lipid peroxide levels and serological markers of myocardial damage, which were significantly suppressed by magnesium. In conclusion, magnesium significantly attenuated excess isoproterenol-induced acute cardiac dysfunction and beta-adrenergic desensitization.

Animals↗
PubMed2006

An oral adsorbent, AST-120, suppresses oxidative stress in uremic rats.

BACKGROUND: The production of reactive oxygen species (ROS) has been suggested to play an important role in the progression of chronic kidney disease (CKD). An oral adsorbent, AST-120, removes uremic toxins such as indoxyl sulfate (IS) and delays the progression of CKD, but the effect on ROS production is unknown. The present study aimed to determine whether AST-120 reduces oxidative stress in uremic rat kidneys using markers of ROS production such as acrolein and 8-hydroxy-2'-deoxyguanosine (8-OHdG). METHODS: Daily administration of AST-120 was started 6 weeks after 5/6 nephrectomy and continued for 18 weeks. The changes in metabolic data, serum and urine IS levels, urinary excretion of markers of oxidative stress, and renal histological findings were investigated in uremic rats with or without AST-120 treatment. RESULTS: In parallel with the increase in serum and urine IS, the serum creatinine, urinary protein and acrolein levels started to increase at 6 weeks, but urinary 8-OHdG remained unchanged and significantly increased at 18 weeks in uremic rats. AST-120 markedly and significantly attenuated increases in uremic toxins and oxidative stress levels as well as the histological changes in glomerular sclerosis, interstitial fibrosis, and the tubular staining of 8-OHdG. CONCLUSION: AST-120 suppressed the progression of CKD, at least in part, via attenuation of oxidative stress induced by uremic toxin.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Caveolin regulates microtubule polymerization in the vascular smooth muscle cells.

Microtubule and caveolin have common properties in intracellular trafficking and the regulation of cellular growth. Overexpression of caveolin in vascular smooth muscle cells increased the polymer form of microtubule without changing in the total amount of tubulin, and downregulation of caveolin decreased the polymer form of microtubule. Fractionation of cellular proteins followed by immunodetection as well as immunostaining of caveolin and microtubule revealed that caveolin and a portion of microtubule were co-localized in caveolar fractions. A caveolin scaffolding domain peptide, which mimics caveolin function, did not alter the polymerization of microtubule in vitro, but dramatically inhibited the depolymerization of microtubule induced by stathmin, a microtubule destabilizing protein, which was also found in caveolar fractions. Accordingly, it is most likely that caveolin increased the polymer form of microtubule through the inhibition of a microtubule destabilizer, stathmin, suggesting a novel role of caveolin in regulating cellular network and trafficking.

Animals↗
PubMed2006

Edaravone diminishes free radicals from circulating neutrophils in patients with ischemic brain attack.

OBJECTIVE: Treatment with a free radical scavenger could be a new option for ischemic brain attack, however, little is known about the alteration of oxidative stress markers induced by edaravone, a novel free radical scavenger, in human ischemic brain attack. METHODS: We investigated the effects of edaravone on the oxidative stress markers in patients with ischemic brain attack. Twenty-one patients with ischemic brain attack and 19 controls were enrolled in this study. Blood samples were obtained just before and soon after the first administration of edaravone (30 mg) or ozagrel (40 mg). Intracellular reactive oxygen species of neutrophils were measured using 6-carboxy-2', 7'-dichlorodihydrofluorescin diacetate and a fluorescence-activated cell sorter. Superoxide from neutrophils, induced by phorbol myristate acetate (PMA), was determined by luminol-amplified chemiluminescence assay. RESULTS: Treatment with 30 mg of edaravone significantly decreased the intracellular reactive oxygen species (ROS) of neutrophils (Wilcoxon test, p=0.0001) and PMA-induced superoxide produced by neutrophils (Wilcoxon test, p=0.001). Ozagrel did not alter the intracellular ROS or superoxide production of neutrophils. CONCLUSION: Reduction of intracellular ROS and suppression of superoxide production in neutrophils provide a potential explanation for the clinical efficacy of edaravone in patients with ischemic brain attack.

Aged↗
PubMed2006

[Takotsubo-like left ventricular dysfunction with delayed recovery of left ventricular shape: a case report].

A 70-year-old woman was admitted to our hospital because of left ventricular dysfunction, which was observed after permanent pacemaker implantation in another hospital. The left ventricular dysfunction was apical ballooning. Left ventriculography demonstrated takotsubo-like shape. However, the dysfunction did not improve immediately with medical treatment. In this case, 75% stenosis was observed in the left anterior descending artery. We suppose that this lesion corresponded to the delayed recovery of the dysfunction and performed coronary intervention. The takotsubo-like shape improved gradually for about 1 year. Whether the coronary intervention was effective for the recovery of the dysfunction is unclear, this clinical course was interesting in evaluating the delayed recovery of takotsubo-like left ventricular dysfunction.

Aged↗
PubMed2006

[Homocysteine].

Explore the source record for details and available documents.

Animals↗
PubMed2005

Hyperinsulinemia is an independent predictor for complex atherosclerotic lesion of thoracic aorta in non-diabetic patients.

OBJECTIVE: Hyperinsulinemia is a well known risk factor for cardiovascular event. However, it is not known whether hyperinsulinemia facilitates atherosclerotic complex lesions of aorta in non-diabetic patients. We investigated whether hyperinsulinemia is an independent marker of severity of atherosclerosis in thoracic aorta of non-diabetic patients using multiplane transesophageal echocardiography (TEE). RESEARCH DESIGN AND METHODS: Non-diabetic 90 patients with cardiovascular disease underwent TEE, and were analyzed for plasma insulin levels of oral glucose tolerance test, conventional atherosclerotic risk factors and coronary angiographic features. RESULTS: Thoracic aortic plaques were detected in 84 patients (93%). The complex atherosclerotic lesions were observed in 35 (39%) patients, most frequently at the part of aortic arch (p<0.005), showing the greatest atheroma score in thoracic aorta (p<0.05). Univariate analysis showed age, male gender, smoking, coronary artery disease, HDL-cholesterol, insulin levels in glucose tolerance test and homeostasis model assessment insulin resistance index (HOMA index) were found to be significant predictors of complex atherosclerotic lesions. Multivariate regression analysis revealed that HOMA index was an independent predictor of complex atherosclerotic lesions (odds ratio 1.93, p=0.006). There was a significant positive correlation between HOMA index and the atheroma score of thoracic aorta (p<0.001). CONCLUSIONS: Hyperinsulinemia is an independent predictor of complex atherosclerotic lesions detected by TEE in the thoracic aorta of non-diabetic patients.

Aged↗
PubMed2005

Tachycardia-induced myocardial ischemia and diastolic dysfunction potentiate secretion of ANP, not BNP, in hypertrophic cardiomyopathy.

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery (n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls (n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 +/- 101 to 1,268 +/- 334 pg/ml (P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM (P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER (r = -0.57, P < 0.01) and tau (r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

Atrial Natriuretic Factor↗
PubMed2005

Ischemic preconditioning enhances scavenging activity of reactive oxygen species and diminishes transmural difference of infarct size.

Reactive oxygen species (ROS) enhance myocardial ischemia-reperfusion (I/R) injury. Ischemic preconditioning (PC) provides potent cardioprotective effects in I/R. However, it has not been elucidated whether PC diminishes ROS stress in I/R and whether PC protects the myocardium from ROS stress transmurally and homogeneously. Isolated rabbit hearts perfused with Krebs-Henseleit buffer underwent 30 min of ischemia and 60 min of reperfusion. Hemodynamic changes and myocardial damage extent were analyzed in four groups. The control group underwent I/R alone. The H2O2 group underwent I/R with H2O2 infusion (50 microM) in the first minute of reperfusion to enhance oxidative stress. The PC and H2O2+PC groups underwent 5 min of PC before control and H2O2 protocols, respectively. Extracted myocardial DNA was analyzed for 8-hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative DNA damage, with the use of the HPLC-electrochemical detection method. Glutathione peroxidase (GPX) activity and the reduced form of GSH were measured by spectrophotometric assays. The myocardial infarct size was significantly reduced in the PC group (19 +/- 2%) compared with the control group (37 +/- 4%; P < 0.05), particularly in the subendocardium. H2O2 transmurally increased the infarct size by 59 +/- 4% (P < 0.05), which was significantly diminished in the H2O2+PC group (31 +/- 4%; P < 0.01). The GSH levels, but not GPX activity, were well preserved transmurally in protocols with PC. The 8-OHdG levels were significantly decreased in PC and were significantly enhanced in H2O2 (P < 0.01). These changes in oxidative DNA damage were effectively diminished by PC. In conclusion, PC enhanced the scavenging activity of GSH against ROS transmurally, reduced myocardial damage, particularly in the subendocardium, and diminished the transmural difference in myocardial infarct size.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Multiple and recurrent systemic thrombotic events associated with congenital anomaly of inferior vena cava.

We describe a case of a 67-year-old woman with a history of cerebral infarction and pulmonary embolism that presented with chest pain. Subsequent evaluation resulted in a diagnosis of acute myocardial infarction and occult DVT, and imaging revealed a rare congenital absence of the infra-renal portion of the inferior vena cava, with lower extremity venous drainage diverted via an ascending lumbar vein. Associations between congenital absence of the inferior vena cava and thrombosis are discussed.

Aged↗
PubMed2005

Controlled-release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension: the NICE Combi (Nifedipine and Candesartan Combination) Study.

OBJECTIVE: To compare the clinical efficacy of low-dose controlled-release (CR) nifedipine (20 mg/day) plus candesartan (8 mg/day) combination therapy with that of up-titrated candesartan (12 mg/day) monotherapy. DESIGN: Randomized, double-blind study. SETTING: Outpatient study. PATIENTS AND PARTICIPANTS: Patients with essential hypertension, who did not achieve their target blood pressure with baseline treatment of candesartan 8 mg/day for 8 weeks. MAIN OUTCOME MEASURES: Blood pressure, pulse pressure, urinary microalbumin excretion. RESULTS: Blood pressure was significantly reduced in both groups (P < 0.05), but the reduction was significantly greater in the combination therapy group (12.1 +/- 1.4/8.7 +/- 0.9 mmHg) than in the up-titrated monotherapy group (4.1 +/- 1.4/4.6 +/- 0.9 mmHg) (P < 0.0001). The reduction in pulse pressure was significantly greater in the combination therapy group (3.3 +/- 1.2 mmHg) than in the up-titrated monotherapy group (0.7 +/- 1.2 mmHg) (P = 0.0031). Urinary microalbumin excretion decreased significantly in the combination therapy group (from 61.9 to 40.5 mg/g creatinine; P < 0.05), but not in the up-titrated monotherapy group. CONCLUSIONS: These findings suggest that the low-dose combination therapy of nifedipine CR and candesartan is superior to the up-titrated monotherapy of candesartan in terms of blood pressure control and renal protection in patients with essential hypertension.

Adolescent↗
PubMed2005

Cost-effectiveness analysis of hypertension treatment: controlled release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension--the Nifedipine and Candesartan Combination (NICE-Combi) Study.

Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/ day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost ("Dominance") were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is "dominant" to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.

Adult↗
PubMed2005

A case of alternating bundle branch block in combination with intra-Hisian block.

We describe a 66-year-old woman who had an alternating bundle branch block consisting of coexisting occurrence of right bundle branch block (RBBB) and left bundle branch block (LBBB) combined with Mobitz type II atrioventricular block (AVB). A prolonged PQ interval was associated with the RBBB pattern whereas it was not apparent in the LBBB pattern. Electrophysiologic study revealed that the LBBB pattern was combined with a double His bundle potential. On the other hand, the RBBB pattern was combined with a markedly prolonged HV interval with a low voltage monophasic His bundle potential, which we speculated was the former part of the split His bundle potential seen during the LBBB pattern. A combination of the longitudinal dissociation in the His bundle and the gap phenomenon at the intra-Hisian block portion may account for this observation.

Aged↗
PubMed2005

[Oxidative stress and magnesium].

The generation of reactive oxygen species and other free radicals during metabolism is a necessary and normal process that ideally is compensated for by an elaborate endogenous antioxidant system. However, due to many environmental, lifestyle, and pathological situations, excess radicals can accumulate, resulting in oxidative stress. Oxidative stress has been related to cardiovascular disease, cancer, and other chronic diseases that account for a major portion of deaths today. Antioxidants are compounds that hinder the oxidative processes and thereby delay or prevent oxidative stress. In this sense, magnesium is one of the physiological, efficient antioxidant. Magnesium plays a role in more than 300 enzymatic reactions and is critically involved in energy metabolism, glucose utilization, protein synthesis, fatty acid synthesis and breakdown, ATPase functions, and virtually all hormonal reactions. This article summarizes the process of oxidative stress and the pathways by which it relates to magnesium.

Animals↗
PubMed2005

[Evidence-based usefulness of Ca antagonists and ACEIs and ARBs for the primary and secondary prevention of major cardiovascular and renal events in patients with hypertension].

The benefits of reducing blood pressure (BP) on the risks of major cardiovascular event and preservation of renal function are well established in patients with hypertension. We estimated effects of strategies based on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) and calcium channel antagonist (CCB), which is predominantly prevalent in Japan in patients with hypertenstion than ACEI/ARB, on the risks of these events, overviewed with data from clinical trials and meta-analysis of these trials including underwent in Japan. ACEI and ARB-based regimens reduced the risks of heart failure and progression of renal dysfunction complicated with and without diabetes mellitus (DM) in patients with hypertension compared with control and CCB-based regimens. CCB-based regimens reduced the primary risks of cerebella event and dementia and primary and secondary risks of coronary events in patients with hypertension having many coronary risk factors compared with control and ARB/ACEI-based regimens. Greater risk reductions, however, were produced by regimens that targeted lower (BP) goals, by combined regimens based on ACEI/ARB and CCB and diuretics, demonstrated in mega-trial of ALLHAT and proposed in guideline of JSH 2004.

Angiotensin Receptor Antagonists↗
PubMed2004

Unequal effects of renin-angiotensin system inhibitors in acute cardiac dysfunction induced by isoproterenol.

Several clinical trials have demonstrated that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) are equally effective in the treatment of chronic heart failure. However, this has not been confirmed for acute cardiac dysfunction. We examined whether ACEI or ARB prevents isoproterenol-induced acute left ventricular (LV) dysfunction in dogs. LV dysfunction induced by a large dose of isoproterenol (1 microg.kg(-1).min(-1), 3-h infusion) was compared in dogs treated with ACEI (temocaprilat) or ARB (olmesartan). Atrial pacing induced a constant heart rate and use of adjustable aortic banding provided a nearly constant afterload. LV systolic function (LV dP/dt, fractional shortening, and ejection fraction) and diastolic function (tau and LV end-diastolic pressure) were significantly deteriorated after isoproterenol infusion. The LV dysfunction was almost totally prevented by ARB but was only partially prevented by ACEI. The partial effect of ACEI was complemented by cotreatment with HOE-140, a bradykinin B2 receptor antagonist. At baseline, the response to low doses of isoproterenol was significantly attenuated by ACEI but not by ARB, and the ACEI-induced attenuation was totally abolished by cotreatment with HOE-140. The response to isoproterenol was significantly attenuated after 3 h of excess isoproterenol loading, and it was almost completely preserved by ARB but not by ACEI. In conclusion, acute LV dysfunction and beta-adrenergic desensitization induced by excess isoproterenol administration were almost totally prevented by ARB but only partially prevented by ACEI. These differences were attributable at least in part to bradykinin pathways activated by ACEI administration in acute LV dysfunction.

Acute Disease↗