Biomedical subjects
E Murakami
Publications and source records attributed to E Murakami.
Effects of some radical scavengers on reperfusion-induced arrhythmias in the canine heart.
In this study, using electron spin resonance (ESR), we investigated the relation at the time of reperfusion between free radicals originating from the mitochondria of the canine myocardium and arrhythmias induced by reperfusion as well as the effect of radical scavengers on both. The left anterior descending artery was ligated just below the first diagonal branch and then reperfused for 10 minutes in 48 adult mongrel dogs. The dogs were divided into six groups consisting of: 1) control group administered no radical scavengers (n = 8), 2) SOD group (n = 6) receiving superoxide dismutase (15,000 U/kg), 3) SOD + CAT group (n = 6) receiving SOD (15,000 U/kg) and catalase (45,000 U/kg), 4) L-SOD group (n = 6) receiving liposomal-encapsulated SOD (30,000 U/kg), 5) CV-3611 (2-O-octadecylascorbic acid) group (n = 8) receiving CV-3611 (10 mg/kg), and 6) CoQ10 group (n = 6) receiving coenzyme Q10 (10 mg/kg). SOD, SOD + CAT, L-SOD, CV-3611, and CoQ10 were administered into the left atrium prior to reperfusion. The second lead of the electrocardiogram was continuously monitored during the experiment. The following results were obtained. 1) The relative intensity (RI) of the electron spin resonance signal of the mitochondria of the reperfused portion of the myocardium was smaller (p less than 0.025) in the SOD, SOD + CAT, L-SOD, CoQ10 groups (1.08 +/- 0.36, 0.92 +/- 0.19, 0.91 +/- 0.11, and 0.81 +/- 0.09, respectively) than in the control group (1.70 +/- 0.20).(ABSTRACT TRUNCATED AT 250 WORDS)
Kidney renin gene expression after renin inhibition in the marmoset.
1. The effects of renin inhibitor ES-8891 on renin synthesis and its secretion by the kidney were investigated in normotensive sodium-depleted marmosets. We measured plasma renin activity, plasma immunoreactive renin concentration, plasma angiotensin II concentration and kidney renin mRNA content after oral administration of ES-8891 (60 mg day-1 kg-1) for 1 week. 2. The mean blood pressure was significantly decreased (P less than 0.01) on day 7 after oral administration of ES-8891. There was no significant change in heart rate during the administration. 3. Oral administration of ES-8891 for 1 week markedly decreased the plasma renin activity, the plasma immunoreactive renin concentration and the plasma angiotensin II concentration (to 18%, 41% and 24% of the corresponding control values; P less than 0.05 for each, n = 5). 4. The kidney renin mRNA content in ES-8891-treated marmosets was significantly lower than that in normal controls (4.2 +/- 3.5 versus 12.8 +/- 5.5 pg/micrograms of total RNA, means +/- SD, P less than 0.05, n = 5). 5. Oral administration of the renin inhibitor ES-8891 for 1 week not only inhibited plasma renin activity but also decreased renin synthesis and its secretion by the kidney.
Disappearance of mitral valve regurgitation after successful percutaneous transluminal coronary angioplasty.
Percutaneous transluminal coronary angioplasty has been reported to improve several clinical parameters. Functional papillary muscle dysfunction, which is also known to induce mitral valve regurgitation, is reversible after revascularization. We described a patient, with a 95% stenosis of proximal right coronary artery, whose mitral valve regurgitation disappeared after successful percutaneous transluminal coronary angioplasty.
[Echocardiographic assessment of the etiology of aortic regurgitation in the elderly].
We performed echocardiographic studies in 189 elderly subjects aged over 65. Aortic regurgitation (AR) was detected by real time 2-D Doppler system. 189 patients were classified into 5 groups based on the severity of AR (AR-: 81 pts, AR1+: 32 pts, AR2+: 44 pts, AR3+: 27 pts, AR4+: 5 pts). The diameter of the aortic root, the angle (theta) between the aortic wall and interventricular septum and echo intensity of aortic valve were measured by 2-D echocardiography. There was no relation between the severity of AR and angle theta. Diameters of aortic root were significantly increased in AR3+ cases as compared with AR- and AR2+. Systolic blood pressure was significantly increased in AR4+ cases as compared with AR-, AR1+, and AR2+. Diastolic blood pressure was also decreased in AR3+ cases as compared with AR-. Echo intensity of aortic valve was increased in patients with AR. It was thought that increased diameters of the aortic root in patients with severe AR were induced from the long-standing AR, and that increased systolic blood pressure and decreased diastolic blood pressure in severe AR were caused by hemodynamic changes due to AR. Therefore, we concluded that AR in the elderly was caused by degeneration and/or deformity of the aortic valve.
Effect of renin inhibitor, ES-8891, on renal renin secretion and storage in the marmoset: comparison with captopril.
We investigated the effects of the human renin inhibitor, ES-8891, and captopril on renal renin secretion and storage in the marmoset. Either ES-8891 (30 mg/kg) or captopril (2 mg/kg) was given orally twice a day for 1 week to conscious, sodium-depleted marmosets (n = 6 for each group). The ES-8891-treated group displayed a significant reduction in mean arterial pressure (MAP), plasma renin activity (PRA) and plasma immunoreactive renin (PIR) compared with the control group. Kidney renin content was significantly increased compared with the control group and enlarged renin granules containing heterogenous internum were observed in juxtaglomerular cells after treatment with ES-8891. Treatment with captopril significantly increased PRA and PIR compared with the control day as well as increasing kidney renin content and the number of renin granules with crystalline content in juxtaglomerular cells compared with the control group. These results suggest that ES-8891 inhibits both PRA and renin secretion from the kidney, resulting in an increase in renal renin storage.
Blood pressure and heart rate variability in elderly patients with isolated systolic hypertension.
To investigate the circadian profiles of BP and heart rate in elderly patients with isolated systolic hypertension (ISH), the variability of BP and heart rate during day time (daytime) and the amplitudes of nocturnal fall were evaluated in ISH (n = 19) comparing with those of essential hypertensive patients (EHT, n = 18) and normotensive subjects (NT, n = 16) in the same age range. ISH showed a significantly wider BP variability during the day time and a greater amplitude of nocturnal fall compared with EHT and NT. However, the heart rate variability during the daytime and the amplitude of nocturnal fall were similar among the three groups. ISH showed a stronger correlation between BP and heart rate during 24 hours compared with EHT and NT. Approximately 80% of ISH showed a significant positive correlation between BP and heart rate. These results suggest that the BP of ISH patients is susceptible to fluctuations in autonomic nerve activity.
[A case of neurofibromatosis 2 combined with a vagal neurilemmoma in the mediastinum].
A 39-year-old man was referred to our hospital for further evaluation of an abnormal mediastinal shadow on chest X-ray film. CT scan of the chest showed a cyst-like tumor in the mediastinum. CT scan of the brain to investigate the impairment of hearing revealed bilateral cerebropontine angle tumors. Histological examination of both tumors revealed neurilemmoma. Neurofibromatosis 2 combined with a vagal neurilemmoma in the mediastinum is very rare.
Effect of renal denervation on the development of hypertension in Dahl-Iwai salt-sensitive rats.
Renal denervation has been shown to delay the onset of hypertension in spontaneously hypertensive rats and DOCA-salt sensitive rats. We investigated the contribution of the renal nerves to the development of hypertension in Dahl-Iwai salt-sensitive (DS) rats. Bilateral renal denervation or sham-operation was carried out in DS rats, and animals were then kept on a high salt diet (study I) or on a normal salt diet (study II). DS rats became severely hypertensive (207 +/- 8 mmHg) after 4 weeks on a high salt diet. They became mildly hypertensive (156 +/- 3 mmHg) after 4 weeks on a normal salt diet. In both studies, renal denervation exerted no effect on the development of hypertension in the DS rats. The urinary sodium excretion, urinary volume, heart rate and body weight were unaltered by renal denervation. These results indicate that the renal nerves do not make a major contribution to the development of hypertension in DS rats.
Plasma atrial natriuretic factor in isolated systolic hypertension in the elderly: response to hypertonic saline infusion.
Plasma immunoreactive atrial natriuretic factor (ANF) and urinary sodium excretion were measured in elderly patients with isolated systolic hypertension (ISH) (n = 11), age-matched essential hypertensive patients (EHT; n = 16) and normotensive subjects (NT; n = 9) before and during a 60 min infusion of hypertonic saline (120 mEq of Na+). An exaggerated natriuresis during the sodium load was observed only in ISH. Baseline plasma ANF levels in ISH were significantly lower (P less than 0.05) than those of EHT and NT. There was no significant change in plasma ANF in EHT and NT subjects after the saline load. In contrast, there was a significant increase in plasma ANF (P less than 0.05) after the saline load in ISH. The change in urinary sodium excretion was significantly correlated with the change in plasma ANF (r = 0.75, P less than 0.01) in ISH. We conclude that an exaggerated natriuresis during a hypertonic saline infusion may be linked to an increase in plasma ANF in elderly ISH patients.
[Evaluation of healing process in myocardial infarction by the time course of serum myosin light chain I: the effects of early reperfusion].
The effects of early reperfusion on the infarct area were evaluated by measuring the plasma creatine phosphokinase (CPK) activity and myosin light chain I (LCI) in 30 patients with acute myocardial infarction. Twenty of these patients underwent coronary angiography, of whom 9 had reperfusion with successful intracoronary thrombolysis, which revealed significant correlations between peak values of LCI and peak values of CPK or CPK-MB activity (r = 0.775, p < 0.01 or r = 0.783, p < 0.01). Similarly, peak value of LCI correlated with left ventricular ejection fraction (r = -0.729, p < 0.01) and the infarct size which was estimated according to the extent and severity scores measured by Tl-201 myocardial SPECT (vs extent score, r = 0.439, p < 0.05; vs severity score, r = 0.429, p < 0.05). The time activity curves of plasma CPK activity and LCI differed in patients with and without reperfusion; in the former, mean peak values of CPK activity and LCI were 1,170 +/- 321 U/L (mean +/- SD) and 10.7 +/- 3.5 ng/ml, respectively, while in the latter, they were 5,430 +/- 3,315 U/L and 25.2 +/- 12.9 ng/ml, respectively. The times to peak values of LCI and CPK did not differ between these 2 patient groups. We concluded that the early reperfusion suppresses the progressive extension of irreversible injury in the infarct area and significantly diminishes the infarct size.
[A case of squamous cell carcinoma of the thymus and thymic cyst].
A 57-year-old man was referred to our hospital for further evaluation of an abnormal mediastinal shadow detected on chest X-ray film. Chest CT showed a solid mass and a cyst. Operation revealed a squamous cell carcinoma of the thymus adjacent to a thymic cyst. Histologic examination demonstrated the clear separation of the squamous cell carcinoma and the thymic cyst by interstitial tissue. Cases of squamous cell carcinoma of the thymus combined with thymic cyst are very rare.
Primary linitis plastica of the descending colon: a case report.
A rare case of primary linitis plastica carcinoma of the colon seen in a 44 year old Japanese man is described herein. The patient had a complete obstruction of the descending colon and was treated with a loop colostomy followed shortly afterward by a left hemicolectomy. At the time of the second operation, the entire thickness of the colonic wall was found to be infiltrated by cancer cells, however, the other intraabdominal organs were free of cancerous involvement. The histopathological diagnosis made at this time was primary linitis plastica carcinoma of the descending colon. Nine months later, the patient developed an intestinal obstruction and relaparotomy revealed diffuse peritoneal dissemination. Two years after the first operation, upper GI films and a gastrofiberscopic examination revealed gastric involvement. The patient died 28 months after his initial operation, and autopsy revealed widespread metastases in the peritoneal surface, paraaortic lymph nodes, small intestine, remaining colon and stomach.
The effect of the renin inhibitor ES-1005 on the expression of the kidney renin gene in sodium-depleted marmosets.
The effect of the renin inhibitor ES-1005 or captopril on the expression of the kidney renin gene was investigated in sodium-depleted marmosets. We measured the level of kidney renin messenger RNA (mRNA) after continuous administration of ES-1005 (48 mg/kg per day) or captopril (2 mg/kg per day) intraperitoneally, via an osmotic mini-pump, for one week. The level of kidney renin mRNA was measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin cDNA fragment as the hybridization probe. Captopril treatment markedly increased plasma renin activity and the level of kidney renin mRNA by 4.7-fold and 6.3-fold, respectively. ES-1005 treatment completely inhibited plasma renin activity and significantly decreased the level of kidney renin mRNA (46% of the normal control P less than 0.01). However, plasma immunoreactive renin concentration was significantly increased by the treatment with ES-1005 (P less than 0.05). These results suggest that the treatment with the renin inhibitor ES-1005 for one week has a paradoxical effect on kidney renin gene expression and renin release from the kidney in sodium-depleted marmosets.
ES-8891, an orally active inhibitor of human renin.
A newly synthesized orally active renin inhibitor, N-morpholinoacetyl-(1-naphthyl)-L-alanyl-(4-thiazolyl)-L-alanyl (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoyl-n-hexylamide (ES-8891), was found to be a highly potent competitive inhibitor of human renin with an inhibition constant of 1.1 nM. This inhibitor was also active against monkey renin, although there was less inhibition of renin in pig, rabbit, and rat. ES-8891 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. A single oral administration of ES-8891 (10 or 30 mg/kg) to conscious, sodium-depleted marmosets caused a dose-related decrease in plasma renin activity and blood pressure. ES-8891 (30 mg/kg) produced an 80% inhibition of plasma renin activity, which lasted for more than 6 hours. Kidney renin messenger RNA was not significantly changed 6 hours after oral administration of ES-8891 (30 mg/kg). A single oral administration of 240 mg ES-8891 to healthy human volunteers (n = 6) produced a significant inhibition of plasma renin activity (75% inhibition at 0.5 and 1 hour, 50% inhibition at 2 hours) with a good correlation of plasma levels of ES-8891. There were no significant changes in blood pressure or heart rate, and no adverse effects were observed. These results suggest that ES-8891 is an orally active human renin inhibitor that may be clinically useful.
[Limitation of experimental infarct size by levo-carnitine chloride (LC-80), a new mitochondrial function-reactivating agent].
The effect of LC-80 on infarct size induced by 6 hr coronary occlusion was studied in anesthetized dogs. LC-80 at a dose of 100 mg/kg, i.v. was injected 5 min after coronary occlusion and then infused at a rate of 50 mg/kg, i.v./hr until the heart was excised. The two risk areas were determined both by injecting a fluorescent dye (Thioflavin S) into the left atrium (in vivo) and by perfusing the non-occluded coronary bed with Monastral Blue (in vitro). The infarct size was determined by topographically tracing the area of myocardium unstained by triphenyltetrazolium chloride. Four zones such as Zone 1 (normal tissue), Zone 2 (tissue characterized by collateral blood flow), Zone 3a (tissue developing necrosis), Zone 3b (necrotic tissue) were delimited . As a result, (1) LC-80 significantly diminished the incidence of ventricular arrhythmias. (2) LC-80 significantly inhibited the decrease in myocardial free carnitine level in Zone 2 and Zone 3b. (3) LC-80 significantly reduced the infarct size expressed as a percentage of the risk area and increased the size of Zone 2. (4) In the electron microscopic findings, LC-80 showed lesser morphological changes such as swollen mitochondria and intracellular and extracellular edema, especially in Zone 2. (5) LC-80 may be useful for inhibiting the evolution of myocardial ischemic cell death both by the protection of ischemic myocardium and presumably by the increase in the collateral blood flow.
Haemodynamic characteristics in elderly patients with isolated systolic hypertension.
Systemic arterial compliance, baroreflex sensitivity index and cardiac function were studied in elderly patients with isolated systolic hypertension (ISH, n = 12) comparing values with those of essential hypertensive patients (EHT, n = 12) and normotensive subjects (NT, n = 7) in the same age range. Systemic arterial compliance of the ISH group was markedly decreased. Baroreflex sensitivity indices of ISH and EHT were similarly decreased. Pre-ejection period index (PEPI) of ISH was normal, whereas PEPI of EHT was significantly longer than that of NT. These results demonstrate that of the haemodynamic characteristics of ISH, the predominant features are a decrease in compliance of large arteries with a disturbance of baroreflex sensitivity and normal cardiac function.
Pressor response to mental stress and exercise in hypertension.
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