Biomedical subjects

K Misumi

Publications and source records attributed to K Misumi.

At least 37 records · Page 2Linked to original sources

PubMed1999

Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction.

OBJECTIVES: We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction. BACKGROUND: Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor. METHODS: In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses. RESULTS: There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group. CONCLUSIONS: This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.

Aged↗

PubMed1999

Experimental His-bundle pacing: histopathological and electrophysiological examination.

His-bundle pacing gives a more physiological ventricular contraction in comparison to right ventricular apical pacing. However the problems of lead fixation and stability of long-term His-bundle pacing are yet unsolved. We used six adult beagles, in which a screw-in lead was anchored in the His-bundle region for observation of the pacing conditions and histopathologic changes of the conduction system over the course of 2 months. In the results, a satisfactory fixation was obtained using a conventional screw-in lead and no histological influence on the conduction system was observed. The pacing threshold at the time of implantation was 1.15 +/- 0.69 V (3.23 +/- 3.08 mA) in the pulse width of 0.5 ms. R wave amplitude, the impedance and slew rate were 7.28 +/- 2.04 mV, 409 +/- 102 Ohm, and 0.65 +/- 0.41 V/s, respectively. Two months later, these parameters changed to 2.83 +/- 1.06 V (10.4 +/- 5.71 mA), 5.63 +/- 1.62 mV, 310 +/- 71.3 Ohm, and 0.49 +/- 0.22 V/s, respectively. These results suggest the feasibility of clinical application of permanent His-bundle pacing.

Animals↗

PubMed1999

Regional blood flow distribution from the proximal arterial cannula during veno-arterial extracorporeal membrane oxygenation in neonatal dog.

Extracorporeal membrane oxygenation (ECMO) is frequently used for treatment of patients with severe hypoxemia due to life-threatening respiratory failure. Due to this hypoxemia, the myocardium of these patients is insufficiently provided with oxygen, and consequently their cardiac function commonly deteriorates. But veno-arterial (V-A) ECMO provides oxygenated blood to the coronary arteries from ECMO circuit insufficiently. To increase the coronary blood flow distributed from ECMO, we placed the arterial cannula 1 cm above the aortic valve and evaluated the regional blood from the proximal arterial cannula in comparison with the distal cannula. Eight neonatal dogs weighting 1.8-2.5 kg were supported by V-A ECMO. The regional blood flow from the arterial cannula was measured by injection of colored microspheres into ECMO circuit. The site of the arterial cannula was changed under fluoroscopy. The bypass flow was maintained at either 50 or 100 ml/min/kg. We found that the coronary blood flow distributed from the proximal arterial cannula was significantly higher than that from the distal cannula. The proximal arterial cannula appears necessary to provide sufficient oxygenated blood to the coronary circulation during V-A ECMO. Therefore, it is expected that the increased cardiac function may improved, and that the survival rate of the patients with retarded cardiac function due to severe hypoxemia may increase by proximal placement of the arterial cannula during V-A ECMO.

Animals↗

PubMed1999

Development of atherosclerotic lesions in cholesterol-loaded rabbits.

To examine both of the target vessels and the optimal time of their endothelial denudation to study vascular restenosis after balloon injury in cholesterol-loaded rabbits, we made 36 atherosclerotic rabbits by feeding a hypercholesterol diet, and histologically examined the onset time and the development of atherosclerosis. Atheromatous changes were observed first after the 5th week in the thoracic aorta from the start of the diet, and then extended to the abdominal aorta, coronary artery with time. The atherosclerotic lesions in the thoracic aorta and the proximal portion of the coronary artery showed high-grade concentric intimal thickening with luminal stenosis. The abdominal aortic lesion mildly progressed. In the renal, carotid and femoral arteries, in contrast, slight atheroscleromatous changes developed during the diet period. These results suggest that the thoracic and abdominal aortas and the coronary artery would be suitable as target vessels to study vascular restenosis after balloon injury, and the endothelial denudation of these vessels should be performed between the 8th and 15th week in this diet protocol for an accurate analysis.

Animals↗

PubMed1999

Salt water promotes hypertension in Dahl-S rats.

Hypertension was induced in Dahl-salt-sensitive (Dahl-S) rats by administering salt in drinking water. Control rats receiving tap water did not show a significant change in blood pressure or abnormalities in the kidney. Rats receiving 0.5% NaCl solution developed moderate hypertension and renal lesions. Rats receiving 1.0% NaCl solution showed prominent and increasing hypertension and severe renal damage. This method of salt administration should be simpler than administration in the diet as a means of promoting renal hypertension. The lower concentration salt water caused chronic mild hypertension in Dahl-S rats, and may serve as a useful model for progressive hypertension.

Animals↗

PubMed1998

Association of remnant lipoprotein levels with impairment of endothelium-dependent vasomotor function in human coronary arteries.

BACKGROUND: It remains undetermined whether triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. METHODS AND RESULTS: The correlation of responses of coronary arterial diameter (quantitative coronary angiography) and coronary blood flow (intracoronary flow wire technique) to intracoronary infusion of acetylcholine (10 and 50 microg/min) with coronary risk factors including remnant lipoprotein levels was statistically analyzed in 106 consecutive subjects with normal coronary angiograms. Remnant lipoproteins were isolated from fasting blood with an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. In multivariate stepwise regression analysis, remnant lipoprotein levels had the most significant correlation with abnormal epicardial coronary vasomotor responses to acetylcholine infusion, reflected by impaired dilation or constriction of the epicardial coronary arteries, and the levels also had an inverse and independent correlation with the coronary blood flow increase in response to acetylcholine. In a subgroup of 53 consecutive subjects, constrictor responses of epicardial coronary diameters to intracoronary infusion of NG-monomethyl-L-arginine (50 micromol/min for 4 minutes) at baseline, reflecting the presence of coronary nitric oxide bioactivity, had an inverse and independent correlation with remnant lipoprotein levels by use of multivariate analysis. CONCLUSIONS: Remnant lipoprotein levels were independently associated with abnormal endothelium-dependent vasomotor function in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor function in human coronary arteries. The decrease in coronary nitric oxide bioactivity may be responsible in part for the inhibitory effects of remnant lipoproteins.

Acetylcholine↗

PubMed1998

Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation.

BACKGROUND: Oxygen free radicals have been shown to cause endothelial vasomotor dysfunction. This study examined the effect of reduced glutathione (GSH), an antioxidant, on human coronary circulation. METHODS AND RESULTS: Responses of epicardial diameter and blood flow of the left anterior descending coronary artery to intracoronary infusion of acetylcholine (ACh, 50 microg/min) were measured by quantitative coronary angiography and Doppler flow-wire technique, respectively, before and during combined intracoronary infusion of GSH (50 mg/min) or saline in 26 subjects with no significant coronary stenosis. GSH infusion suppressed the constrictor response of epicardial diameter to ACh and enhanced the increase in blood flow response to ACh. Furthermore, GSH potentiated the coronary dilator effect of nitroglycerin. A beneficial effect of GSH on the epicardial diameter response to ACh was observed in a subgroup of subjects with > or = 1 coronary risk factors but not in a subgroup without risk factors. Saline infusion did not have any effects. CONCLUSIONS: The results indicate that GSH improved coronary endothelial vasomotor function, particularly in subjects with coronary risk factors, and it potentiated the vasodilator effect of nitroglycerin in human coronary arteries.

Acetylcholine↗

PubMed1998

Serial changes in plasma levels of soluble P-selectin in patients with acute myocardial infarction.

The present study examines whether an acute inflammatory response occurs during acute myocardial infarction (AMI) by measuring soluble P-selectin levels. We examined plasma soluble P-selectin levels in 16 consecutive patients with AMI, in 15 patients with angina, and in 13 control subjects with chest pain but normal coronary arteries and no coronary spasm. In patients with AMI, blood samples were obtained immediately after admission and at 1, 4, 24, and 48 hours, and 1 week after initiation of reperfusion therapy. The plasma soluble P-selectin levels were significantly higher in the AMI group on admission than in the other 2 groups (83 +/- 13 ng/ml, p < 0.01). The plasma soluble P-selectin levels at baseline were not significantly different between the angina and control groups (28 +/- 4 vs 24 +/- 5 ng/ml, p = NS). Plasma soluble P-selectin levels reached their peak significantly at 4 hours after initiation of the reperfusion therapy in patients with AMI. The peak level was significantly higher than the level on admission (115 +/- 17 vs 83 +/- 13 ng/ml, p < 0.05). The plasma soluble P-selectin levels were higher in the AMI group than in the angina and control groups over the time course (p < 0.01). Our data indicate that the plasma soluble P-selectin levels are increased in patients with AMI, and that the levels are increases after reperfusion therapy more than before reperfusion. We suggest that the increase in the plasma soluble P-selectin levels may be caused by the activation of endothelial cells and platelets after myocardial ischemia and reperfusion during AMI.

Aged↗

PubMed1998

Heparin-releasable endothelial cell-associated tissue factor pathway inhibitor (TFPI) is increased in the coronary circulation after coronary spasm in patients with coronary spastic angina.

Tissue factor pathway inhibitor (TFPI) is a physiological regulator of the extrinsic coagulation cascade. Coronary spasm can alter endothelial cell properties in the coronary artery with resultant thrombosis. To determine whether coronary spasm affects plasma TFPI level, we measured the heparin-releasable endothelial cell-associated TFPI (heparin-releasable TFPI) (ng/ml) in the coronary sinus and the aortic root before and after coronary spasm induced by an injection of acetylcholine in 18 patients with coronary spastic angina, and before and after myocardial ischemia induced by rapid atrial pacing in 18 patients with stable exertional angina, and in 17 control subjects with normal coronary arteries and no coronary spasm. Heparin-releasable TFPI level in the coronary spastic angina group significantly increased in the coronary sinus (1 22+/-46 to 147+/-63, p<0.001) after the ischemic event but not in the aortic root (113+/-44 to 121+/-58). The level in the coronary sinus and the aortic root remained unchanged after the ischemic event in the stable exertional angina group and after the injection of acetylcholine in the control group. The coronary sinus-arterial difference in the amount of the heparin-releasable TFPI significantly increased after the ischemic event only in the coronary spastic angina group (10+/-18 to 26+/-18, p<0.002). Our result suggested that heparin-releasable TFPI is increased in the coronary circulation after coronary spasm.

Aged↗

PubMed1998

Comparison of plasma tissue factor levels in unstable and stable angina pectoris.

We have reported that the plasma levels of plasma fibrinopeptide A and plasminogen activator inhibitor activity increase in patients with unstable angina and acute myocardial infarction. Tissue factor (TF) is a low-molecular-weight glycoprotein that binds to and acts on essential cofactor VII, and the resulting complex activates factors IX and X, initiating the coagulation cascade. We measured plasma TF antigen levels in 21 patients with unstable angina (on admission and after treatment), 27 patients with stable exertional angina, and 27 control subjects. The 3 groups were matched for age, gender, and other clinical variables. The plasma TF antigen levels were higher in the unstable angina group than in the stable exertional angina and control groups (240 +/- 75 vs 184 +/- 46 and 177 +/- 37 pg/ml, p < 0.01). There were no significant differences in the plasma TF antigen levels between the stable exertional angina and the control groups. Furthermore, the plasma TF antigen levels were reexamined after treatment in the 21 patients with unstable angina. The mean level in these 21 patients decreased after 2 weeks of treatment (from 240 +/- 75 to 206 +/- 57 pg/ml, p < 0.01). This study suggests that the plasma TF antigen levels correlate with disease activity in patients with unstable angina. The increased plasma TF antigen levels in patients with unstable angina may reflect intravascular procoagulant activity.

Adult↗

PubMed1998

Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina.

OBJECTIVES: This study sought to examine effect of vitamin C, an antioxidant, on the abnormal vasomotor reactivity in spasm coronary arteries. BACKGROUND: Oxygen free radicals generated in the arterial walls have been shown to cause endothelial vasomotor dysfunction. METHODS: Responses of the epicardial arterial diameters of the left coronary arteries to the intracoronary infusion of acetylcholine (ACh) (10 and 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of vitamin C (10 mg/min) or saline as a placebo in 32 patients with coronary spastic angina and in 34 control subjects. RESULTS: Vitamin C infusion suppressed the constrictor response of the epicardial diameter to ACh in spasm coronary arteries but had no significant effect in the control coronary arteries (percent change in distal diameter in response to 10 microg/min of ACh [constriction (-), dilation (+), mean +/- SEM] before vitamin C: -8.2 +/- 2.9% in spasm arteries, +8.4 +/- 2.9%* in control arteries; during vitamin C: +0.2 +/- 3.8%* in spasm arteries, +7.2 +/- 1.3%* in control arteries [*p < 0.01 vs. spasm arteries before vitamin CI). The coronary sinus-arterial difference in plasma thiobarbituric acid reactive substances during ACh infusion, an indicator of lipid peroxidation in coronary circulation, was higher in patients with coronary spastic angina than in control subjects (p < 0.01) but was suppressed in patients with coronary spastic angina to comparable levels in control subjects by combined infusion of vitamin C. Saline infusion had no effect. CONCLUSIONS: The results indicate that vitamin C attenuates vasomotor dysfunction in epicardial coronary arteries in patients with coronary spastic angina. Oxygen free radicals may at least in part play a role in the abnormal coronary vasomotor reactivity in response to ACh in spasm coronary arteries.

Acetylcholine↗

PubMed1998

Circadian variation in plasma levels of free-form tissue factor pathway inhibitor antigen in patients with coronary spastic angina.

Tissue factor pathway inhibitor (TFPI) is known to inhibit the initial reaction in the tissue factor-mediated coagulation pathway. We measured plasma free-form TFPI antigen levels and monitored 24-h Holter recordings at 06.00, 14.00 and 22.00 h in 15 patients with coronary spastic angina, 13 patients with stable exertional angina, and 11 control subjects. There was a significant circadian variation in plasma free-form TFPI antigen levels in patients with coronary spastic angina (25.8+/-2.0 ng/ml at 06.00 h, 21.1+/-1.6 ng/ml at 14.00 h, and 20.2+/-1.4 ng/ml at 22.00 h; p<0.01). Furthermore, free-form TFPI antigen levels at 06.00 h were significantly higher in coronary spastic angina patients than in patients with stable exertional angina or control subjects (p<0.01). Free-form TFPI antigen levels increased after the ischemic attacks in coronary spastic angina (p<0.01). This circadian variation correlated with the frequency of attacks, with the peak level occurring between midnight to early morning in patients with coronary spastic angina.

Adult↗

PubMed1998

Simultaneous elevation of the levels of circulating monocyte chemoattractant protein-1 and tissue factor in acute coronary syndromes.

The levels of circulating monocyte chemoattractant protein-1 (MCP-1) and tissue factor (TF) were examined on admission in 46 consecutive patients with acute coronary syndromes (ACS) and 30 patients with stable exertional angina (SEA). The plasma levels of both MCP-1 and TF were higher in the ACS patients than in the SEA patients (MCP-1: p<0.001; TF: p<0.001). Only the circulating TF level related to the number of diseased vessels. A positive correlation between plasma MCP-1 and TF levels was found (r=0.476, p<0.001). These results suggest that circulating MCP-1 plays an important role in the pathogenesis and/or development of ACS.

Acute Disease↗

PubMed1998

Circulatory arrest under hypothermic anesthesia using abdominal cavity cooling.

The purpose of this study was to investigate the potential for circulatory arrest during surgery under systemic hypothermic anesthesia, using the abdominal cavity cooling method. Eighteen beagles, each weighing 10.5 +/- 2.3 kg, were cooled by filling the abdominal cavity with crushed ice. Just after the esophageal temperature reached 30 degrees C, the heart was exposed, and a left-heart bypass from the left atrium to the aortic root was created. At 20-23 degrees C, the heart was arrested by infusing cooled Young's solution into the aortic root. After a period of cardiac arrest, resuscitation and rewarming were initiated simultaneously. Throughout these procedures, an electrocardiogram (ECG) and the arterial blood pressure (ABP) were monitored continuously. Hematocrit (Ht), total protein (TP), and arterial blood pH and gases were measured every 30 min. The recoveries after surgery were divided into three types as follows, 1) recovery without any complications-11 dogs, 2) not extubated with spontaneous breathing-4 dogs, 3) no reappearance of heart beat-3 dogs. PaO2 during resuscitation was significantly higher in dogs which recovered completely than in the rest of the dogs. These results suggest that hypothermia induced by the abdominal cavity cooling method could be useful for organ-protection during open-heart surgery, and that successful recovery may be attained through protection of the lung as well as the myocardium.

Abdomen↗

PubMed1998

Relationship between serum angiotensin-converting enzyme activity and plasma plasminogen activator inhibitor activity in patients with recent myocardial infarction.

BACKGROUND: An elevated level of angiotensin-converting enzyme (ACE) has been demonstrated to increase the risk of myocardial infarction. Plasminogen activator inhibitor (PAI) is the most important physiological inhibitor of tissue plasminogen activator in plasma. An elevated level of PAI has been reported to be associated with decreased fibrinolytic capacity and to constitute a marker of the risk for recurrent coronary thrombosis. METHODS: We measured the serum ACE activity and plasma PAI activity in 34 patients with recent myocardial infarction, and evaluated the correlation between these two values by linear regression analysis. We also administered captopril (37.5 mg/day) to 17 of these patients and placebo to the other 17 patients at random, and compared the changes in PAI activity and ACE activity in these two groups over a 1-month period. RESULTS: There was a significant correlation between the serum ACE activity and the plasma PAI activity at baseline in the patients (r = 0.498, P < 0.01). The captopril-treated patients showed significantly reduced PAI activity (P < 0.01), and a concomitant decrease in ACE activity. CONCLUSION: These results suggest that elevated ACE activity is associated with impaired fibrinolysis and that treatment with an ACE inhibitor improves the fibrinolytic function in patients with recent myocardial infarction. The results also suggest that the renin-angiotensin system plays a role in the increased risk of ischemic cardiovascular events when it is activated, and in the reduction of risk of recurrent myocardial infarction by ACE inhibition.

Adult↗

PubMed1997

Syntheses and antifungal activity of dl-griseofulvin and its congeners. III.

Several congeners (1b-g), with novel substituents on the benzene ring of griseofulvin, were prepared by the application of a synthetic method developed by us. Antifungal activity of these congeners decreased in order of dl-griseofulvin (1a) = 1d > 1b, c >> 1e-f (inactive). The relationship between the antifungal activity and the position or kind of substituents on the benzene ring of griseofulvin is discussed.

Antifungal Agents↗

PubMed1997

Syntheses and antifungal activity of dl-griseofulvin and its congeners. II.

Griseofulvin derivatives, dl-6'-demethyl-6'-ethylgriseofulvin (dl-5) and dl-6'demethyl-6'phenylgriseofulvin (dl-6) were prepared by application of a synthetic method developed by us. Antifungal activity of these derivatives decreased in the order of dl-griseofulvin (dl-1) >> dl-6(inactive). The reaction of these derivatives with ethanethiol gave two types of compounds, 2'-(ethylthio)griseofulvin (15) and 4'-(ethylthio)isogriseofulvin (16). The relationship between the ratios of isolated yield of 15 and 16 and antifungal the activity of griseofulvin derivatives is discussed.

Antifungal Agents↗

PubMed1997

The effects of medetomidine on maternal and fetal cardiovascular and pulmonary function, intrauterine pressure and uterine blood flow in pregnant goats.

To investigate the effects of medetomidine on late pregnant goats, medetomidine induced changes in maternal or fetal circulation and acid-base balance, as well as changes in intrauterine pressure (IUP) and uterine blood flow (UBF), were studied. Intramuscular administration of medetomidine (40 micrograms/kg b.w.) decreased the heart rate (HR) and arterial blood pressure (ABP) of the mother, and the change in HR was significant statistically (p < 0.05). In the fetus, HR and ABP showed a transient decrease and increase (p < 0.05), respectively. A decrease in maternal arterial blood pH and oxygen partial pressure (PO2) and an increase in carbon dioxide partial pressure (PCO2) were recorded after the injection, but none was significant. In the fetus, arterial blood PO2 decreased significantly (p < 0.05) after 5 min of administration, and a significant metabolic acidemia supported by a decrease in base excess was observed. Within 1 to 4 min after the administration of medetomidine, IUP began to rise and remained high for 10 to 14 min. Thereafter, the rise in IUP was frequent and periodical. After the injection, UBF significantly (p < 0.05) decreased, and the fall in UBF was associated with a rise in IUP. The maternal and fetal serum medetomidine concentration increased remarkably after the injection of medetomidine into the mother. These observations in late pregnant goats suggested that medetomidine induced a decrease in maternal cardiac output, a decrease in UBF arising from the induction of uterine contractions, and transplacental medetomidine can have a suppressive effect on the fetus.

Adrenergic alpha-Agonists↗