Biomedical subjects

Tetsuji Miura

Publications and source records attributed to Tetsuji Miura.

42 records · Page 3Linked to original sources

PubMed2002

Blockade of the Na+-Ca2+ exchanger is more efficient than blockade of the Na+-H+ exchanger for protection of the myocardium from lethal reperfusion injury.

Since the Na(+)-H(+) exchanger (NHE) is not the only pathway of Na(+) influx into cardiomyocytes during ischemia/reperfusion, we hypothesized that blockade of Na(+)-Ca(2+) exchanger (NCX) may be a more efficient strategy than is NHE inhibition for protecting the myocardium from infarction. To test this hypothesis, we compared KB-R7943 (KBR), a novel selective NCX blocker, with cariporide, a selective NHE blocker, with regard to their protective effects against infarction. In isolated rabbit hearts, infarction was induced by 30-min global ischemia/2-h reperfusion, and infarct size was determined by tetrazolium staining and expressed as a percentage of area at risk (%IS/AR). Hearts received no drugs, or were infused with cariporide (1 microM) for 10 min or KBR (0.3 or 10 microM) for 5 min before ischemia or after the onset of reperfusion. Protein level of NCX was assessed by Western blotting. Cariporide infusion before ischemia significantly reduced %IS/AR from 63.9 +/- 2.9% to 20.2 +/- 3.0%, but its infusion upon reperfusion failed to achieve a significant protection (%IS/AR = 53.8 +/- 4.6%). In contrast, KBR infusion similarly reduced infarct size both when infused before ischemia (%IS/AR = 33.3 +/- 6.3% and 21.9 +/- 4.7% by 0.3 and 10 microM KBR, respectively) and when infused for only 5 min after reperfusion (%IS/AR = 35.3 +/- 7.1% and 31.5 +/- 2.1% by 0.3 and 10 microM KBR, respectively). Protein levels of NCX after 30-min ischemia and 30-min ischemia/30-min reperfusion were similar to baseline values in both untreated controls and hearts treated with 0.3 microM KBR upon reperfusion. These results suggest that lethal reperfusion injury is more efficiently suppressed by blockade of the NCX than by blockade of the NHE.

Animals↗

PubMed2002

Sonoclot coagulation analysis: new bedside monitoring for determination of the appropriate heparin dose during haemodialysis.

BACKGROUND: Thrombotic and haemorrhagic complications affect cardiovascular morbidity and mortality in haemodialysis patients. We investigated whether a new bedside Sonoclot analysis is useful for determining an appropriate heparin dose during haemodialysis. METHODS: Twenty-two haemodialysis patients (15 males and seven females) treated with unfractionated heparin were recruited. Sonoclot parameters, including activated clotting time (ACT), clot rate (CR), time to peak (TP) and peak amplitude (PA), were examined before and after haemodialysis, coupled with conventional coagulable variables, platelet count and fibrinogen level. Some indices were determined and verified to control heparin dose. Thrombotic and haemorrhagic complications were observed for 3 months. Sonoclot analysis was subsequently performed before initiation, 1 h later, 2.5 or 3 h later (before cessation of heparin infusion), and at the end of haemodialysis. RESULTS: Both CR and PA were positively correlated with platelet count and fibrinogen level. Sonoclot parameters except for PA were significantly correlated with heparin dose. Heparin dose was reduced without causing complications in 12 patients with DeltaACT >/=40 s and/or CR after haemodialysis (CRpost) <20 U/min. Thrombotic complications occurred in five patients who had CRpost >30 U/min. ACT and TP increased during heparin treatment. ACT was reversed but TP did not change after cessation of heparin. CR significantly decreased after initiation of heparin and was reversed, although not completely, after cessation of heparin. PA showed no significant changes during haemodialysis. CONCLUSIONS: Sonoclot analysis can monitor accurate coagulable states and determine an appropriate heparin dose during haemodialysis.

Blood Coagulation Tests↗

PubMed2002

Blockade of angiotensin II type 1 receptors suppressed free radical production and preserved coronary endothelial function in the rabbit heart after myocardial infarction.

The hypothesis that blockade of angiotensin II type 1 (AT1) receptors after myocardial infarction prevents coronary endothelial vasomotor dysfunction by suppressing oxygen free radical production was examined. Rabbits underwent coronary ligation or a sham operation with or without infusion of valsartan, an AT 1 receptor blocker. Two weeks after the operation, the heart was isolated from each rabbit and perfused with buffer in the Langendorff mode, and coronary flow responses to acetylcholine and sodium nitroprusside were assessed. The ratio of heart weight to body weight and the lipid peroxide level in the myocardium were increased by 30 and 50%, respectively, 2 weeks after infarction. The coronary flow response to acetylcholine (10(-8) to 10(-5) M) was reduced by 50% in the hearts with infarction compared with the sham controls, although coronary flow responses to sodium nitroprusside were similar. The coronary flow response to acetylcholine in the hearts with infarction was restored by concurrent infusion of N -2-mercaptopropionyl-glycine, a free radical scavenger. Valsartan (10 mg/kg/d) infused after infarction prevented both ventricular remodeling and elevation of the tissue lipid peroxide level and preserved coronary flow response to acetylcholine. In conclusion, long-term AT1 receptor blockade after infarction protects the coronary arteries from endothelial vasomotor dysfunction through suppression of free radical production.

Acetylcholine↗

PubMed2002

Opening of mitochondrial K(ATP) channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning.

We examined whether the mitochondrial ATP-sensitive K channel (K(ATP)) is an effector downstream of protein kinase C-epsilon (PKC-epsilon) in the mechanism of preconditioning (PC) in isolated rabbit hearts. PC with two cycles of 5-min ischemia/5-min reperfusion before 30-min global ischemia reduced infarction from 50.3 +/- 6.8% of the left ventricle to 20.3 +/- 3.7%. PC significantly increased PKC-epsilon protein in the particulate fraction from 51 +/- 4% of the total to 60 +/- 4%, whereas no translocation was observed for PKC-delta and PKC-alpha. In mitochondria separated from the other particulate fractions, PC increased the PKC-epsilon level by 50%. Infusion of 5-hydroxydecanoate (5-HD), a mitochondrial K(ATP) blocker, after PC abolished the cardioprotection of PC, whereas PKC-epsilon translocation by PC was not interfered with 5-HD. Diazoxide, a mitochondrial K(ATP) opener, infused 10 min before ischemia limited infarct size to 5.2 +/- 1.4%, but this agent neither translocated PKC-epsilon by itself nor accelerated PKC-epsilon translocation after ischemia. Together with the results of earlier studies showing mitochondrial K(ATP) opening by PKC, the present results suggest that mitochondrial K(ATP)-mediated cardioprotection occurs subsequent to PKC-epsilon activation by PC.

Adenosine Triphosphate↗

PubMed2002

Hepatocyte growth factor and 24-hour ambulatory blood pressure monitoring.

In recent years, many growth factors and cytokines have been shown to be related to arteriosclerosis, and hepatocyte growth factor (HGF) has been reported to be associated with hypertension. In the present study, we investigated the relationship between HGF and hypertension by measuring the serum HGF concentration and performing 24-h ambulatory blood pressure monitoring (ABPM) in 47 randomly selected male and female subjects who underwent a medical examination for cardiovascular disease. The results were as follows. 1) The mean serum HGF concentration in the subjects was 0.35+/-0.14 ng/ml. 2) The serum HGF concentration was positively correlated with both the nighttime systolic and diastolic blood pressures (r=0.42, p<0.05 and r=0.47, p<0.01, respectively). 3) No correlation was found between serum HGF concentration and daytime systolic or diastolic blood pressure. 4) When subjects were divided into two groups based on the difference between daytime and nighttime systolic blood pressure, i.e., a group in which the difference was less than 10 mmHg and a group in which the difference was 10 mmHg or more, the HGF concentration was significantly higher in the former group (0.39+/-0.14 vs. 0.30+/-0.12 ng/ml, p<0.05); similarly, when subjects were divided into a group in which the difference between daytime and nighttime diastolic blood pressure was 5 mmHg and a group in which the difference was 5 mmHg or more, the HGF concentration was significantly higher in the former group (0.42+/-0.15 vs. 0.31+/-0.12 ng/ml, p<0.05). The results indicated that there is a relationship between blood pressure measured by ABPM and serum HGF concentration, and that this relationship might be an index of damage to blood vessels in patients with hypertension.

Aged↗

PubMedDate not supplied

Intracardiac fibroblasts, but not bone marrow derived cells, are the origin of myofibroblasts in myocardial infarct repair.

UNLABELLED: Origin of myofibroblasts in infarcted myocardium was examined by using rats in which bone marrow of green fluorescent protein (GFP)-transgenic mice had been transplanted. GFP was not detected in myofibroblasts at either 3 or 7 days after infarction, suggesting that proliferating myofibroblasts in infarcted myocardium are derived from resident fibroblasts rather than circulating precursor cells of bone marrow origin. BACKGROUND: Myofibroblasts play important roles in the repair process of myocardial infarct, and their origin has been assumed to be interstitial fibroblasts in the heart. However, bone marrow-derived myofibroblasts have recently been identified in pathological fibrosis in extracardiac tissues. In this study, we aimed to determine whether some of the myofibroblasts in infarcted myocardium are derived from circulating precursor cells of bone marrow origin. METHODS AND RESULTS: Bone marrow (BM) of GFP-transgenic mice was transplanted into nude rats, and their coronary arteries were occluded for 60 min and reperfused for 3 or 7 days. Non-BM-transplanted rats served as controls. At 3 days after infarction, some endothelial cells were GFP-positive, indicating that they were of bone marrow origin. Predominant cells in infarcted regions were macrophages and neutrophils, and there were only a small number of vimentin-positive cells and fewer myofibroblasts, both of which were GFP-negative. At 7 days after infarction, there were numerous myofibroblasts in granulation tissue replacing necrotic myocytes, and none of them showed GFP signals, whereas some cells were positive for both GFP and vimentin. Appearance of myofibroblasts and extent of the infarct repair in BM-transplanted and those in non-transplanted rats were similar. CONCLUSIONS: The findings in this study suggest that proliferating myofibroblasts in infarcted myocardium are derived from resident fibroblasts rather than circulating precursor cells of bone marrow origin.

Animals↗