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Biomedical subjects

Y Koiwaya

Publications and source records attributed to Y Koiwaya.

At least 37 records · Page 2Linked to original sources

Adrenomedullin: a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes.

Adrenomedullin (AM), a potent vasodilator peptide, exists in the cardiac ventricle; however, the role of AM in the ventricular tissue remains unknown. In the present study, we investigated the production and secretion of AM in cultured neonatal rat cardiomyocytes, and we examined the effect of AM on de novo protein synthesis in these cells by measuring [14C]phenylalanine incorporation. The cardiomyocytes cultured with serum-free media secreted AM into the media in a time-dependent manner at the rate of 12.2+/-0.5 fmol/10(5) cells/48 hours (mean+/-SEM). Angiotensin II (1 micromol/L) or 10% fetal bovine serum significantly (P<.01) increased the AM secretion by 115% and 305%, respectively. In addition, Northern blot analysis of total RNA extracted from the myocytes disclosed the expression of prepro-AM mRNA of 1.6 kb. Synthetic AM at 1 micromol/L significantly reduced the 10(-6) mol/L angiotensin II- and 10% fetal bovine serum-stimulated [14C]phenylalanine incorporation into the cells, by 16% (P<.05) and 20% (P<.01), respectively. The inhibitory effect of AM on the angiotensin II-stimulated [14C]phenylalanine incorporation was abolished dose-dependently by a calcitonin gene-related peptide receptor antagonist, CGRP(8-37). Furthermore, blockade of the action of endogenous AM by either 10(-6) mol/L CGRP(8-37) or anti-AM monoclonal antibody significantly enhanced the basal and 10(-6) mol/L angiotensin II-stimulated [14C]phenylalanine incorporation. In summary, cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth.

Adrenomedullin↗

Magnetic resonance imaging of Bland-White-Garland syndrome--a case of anomalous origin of the left coronary artery from the pulmonary trunk in a 22-year-old woman.

Selective right coronary angiography in a 22-year-old woman demonstrated an enormous right coronary artery, with the contrast medium opacifying to the left coronary artery through a well-developed collateral circulation and draining into the pulmonary artery. The diagnosis of anomalous origin of the left coronary artery from the pulmonary trunk [also known as Bland-White-Garland (BWG) syndrome] was thus established. Magnetic resonance imaging (MRI) showed a dilated right coronary artery arising from the aorta, the left coronary artery from the pulmonary trunk but not from the aorta, and well-developed channels in the interventricular septum. MRI could be a useful tool for diagnosing anomalous origin of the left coronary artery from the pulmonary trunk.

Coronary Vessel Anomalies↗

Decrease in circulating and urine adrenomedullin concentrations in stroke-prone spontaneously hypertensive rats.

Adrenomedullin (AM) is a peptide with potent vasodilatory and hypotensive properties. Plasma AM levels in rats with experimentally induced hypertension, such as Dahl salt-sensitive rats and two-kidney, one-clip hypertensive rats, are higher than those in normotensive rats. We previously noted, however, that plasma AM levels in spontaneously hypertensive rats (SHR) are similar to those in Wistar-Kyoto rats. To define the role of AM in rats with severe hypertension, we investigated changes in circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm). The immunoreactive rat AM levels in plasma, urine, and tissue measured with a sensitive radioimmunoassay, and the AM mRNA levels in various tissues in 15-wk-old SHRSP/Izm were compared with those in age-matched Wistar-Kyoto rats (WKY/Izm). The plasma and urinary AM levels in SHRSP/Izm were significantly lower than those in WKY/Izm [plasma AM, 2.14+/-0.06 (SE) vs. 3.24+/-0.16 fmol/ml, p< 0.001; urinary AM, 16.36+/-3.21 vs. 36.12+/-6.09 fmol/ml, p< 0.01]. A negative correlation was found between the plasma AM level and the systolic blood pressure in both SHRSP/Izm and WKY/Izm. Reverse-phase high-performance liquid chromatography showed that the molecular components of plasma immunoreactive AM in SHRSP/Izm were similar to those in WKY/Izm. Furthermore, tissue AM levels in various organs in SHRSP/Izm were not lower than those in WKY/Izm. In conclusion, low levels of circulating AM may contribute to the maintenance of high blood pressure in 15-wk-old SHRSP/Izm. These low plasma AM levels may be caused by accelerated metabolism of circulating AM in SHRSP/Izm.

Adrenomedullin↗

[Coronary angiography provides considerable in vivo pathophysiological information on coronary artery disease].

Coronary cineangiography (CAG) has various limitations and pitfalls, but is widely accepted for evaluating coronary circulation. The interpretation of CAG focuses mainly on the extent and location of coronary artery disease. However, CAG can also provide considerable and varied in vivo pathophysiological information on coronary artery disease as follows: Certain in vivo angiographic coronary morphologies are indicative of histological findings, such as ruptured atheromatous plaque with/without overlying thrombus. Such morphologies are commonly found in patent ischemia- or infarct-related arteries of patients with acute coronary events in both the acute phase and one month after standard medication, and the diseased portion with the morphology is highly specific to the culprit site. The rupture of plaque and overlaid thrombus is just as important in patients with acute coronary events who survive as in patients who die. Diseased sites with complex lesions are prone to progress toward clinical ischemic episodes. The severity of coronary narrowing immediately after acute coronary events does not influence later left ventricular function if antegrade coronary blood flow without distal filling delay is preserved. Coronary stenosis induced by plaque rupture and superimposed thrombus is likely to improve or disappear with time and/or anticoagulant administration with/without antiplatelet therapy. Such information derived from CAG may improve the understanding and suggest optimal therapeutic strategies of coronary artery disease for individual patients.

Coronary Angiography↗

Stress technetium-99m tetrofosmin myocardial scintigraphy: a new one-hour protocol for the detection of coronary artery disease.

A one-hour protocol for stress myocardial scintigraphy using technetium-99m (99mTc) tetrofosmin was compared with scintigraphy using thallium-201 (201Tl) for the detection of coronary artery disease in 43 consecutive patients who underwent stress 201Tl and 99mTc-tetrofosmin myocardial scintigraphy, and coronary arteriography within 1 week. For the stress 99mTc-tetrofosmin test, rest imaging data were acquired 20 min after intravenous injection of 5-7 mCi 99mTc-tetrofosmin, using a 3-head gamma camera collecting 20-sec views over 360 degrees. After dobutamine infusion or bicycle ergometer exercise, 20-25 mCi of 99mTc-tetrofosmin was additionally injected at peak stress. The stress images were acquired 15 min after the second injection with 5-sec views over 360 degrees. All patients also underwent 201Tl exercise and redistribution (4-hour) imaging following a standard protocol. The overall sensitivity for detecting coronary artery disease was 96.0%, with an overall specificity of 93.3% for both types of scintigraphy. Qualitative analyses of 21 conventionally divided left ventricular segments showed that the overall segmental concordance between the 99mTc-tetrofosmin and 201Tl imagings was 85.2% on the rest images and 82.1% on the stress images. The segmental concordance of the rest images was 87.0% in patients with neither significant stenosis nor myocardial infarction, 86.2% in patients with significant stenosis without myocardial infarction, and 82.9% in patients with significant stenosis and myocardial infarction, and the concordance values of the stress images were 85.4%, 87.5% and 75.6%, respectively. These preliminary results suggest that stress myocardial scintigraphy using the present new protocol is a promising approach for the detection of coronary artery disease, with diagnostic sensitivity and specificity comparable to those of stress 201Tl scintigraphy.

Coronary Angiography↗

Recurrent syncope induced by left ventricular outflow tract obstruction: demonstration in a patient with hypertrophic obstructive cardiomyopathy.

A 70-year-old man presented with repeated syncope induced by left ventricular outflow tract obstruction. He was referred to us because of repeated syncope with convulsion at rest. During syncope, electrocardiography showed marked ST segment depression with negative T waves in leads I, II, aVL, aVF and V2-V5 but no arrhythmias. Echocardiography revealed asymmetric septal hypertrophy and complete obstruction of the left ventricular outflow tract due to systolic anterior movement of anterior mitral leaflet and concomitant severe mitral regurgitation. During the catheterization study, syncope with convulsion developed repeatedly without antecedent cause, and was associated with a decrease in systemic blood pressure. Simultaneous pressure monitoring of the left ventricle and femoral artery showed a significant pressure gradient (maximum 110 mmHg). During each episode, systemic blood pressure rose spontaneously with the recovery of consciousness over several minutes. He received temporary atrioventricular sequential pacing and underwent successful mitral valve replacement. Four years later, he was doing well.

Aged↗

Increased plasma adrenomedullin levels in chronic congestive heart failure.

Adrenomedullin is a potent vasodilator peptide and occurs in circulating blood of human beings and experimental animals. Because it is produced in intact aorta of rats and in cultured vascular endothelial cells, adrenomedullin seems to participate in regulation of local vascular tone. To determine the pathophysiological roles of adrenomedullin, we investigated its plasma concentrations in 49 patients with heart failure. Plasma adrenomedullin levels increased significantly with advancing severity of the disease (New York Heart Association functional class I, 4.1 +/- 1.0; II, 5.6 +/- 1.6; III, 6.4 +/- 0.8; IV, 13.2 +/- 6.8 (fmol/l). Plasma adrenomedullin was correlated with pulmonary artery pressure (r = 0.44, p = 0.0114) and pulmonary capillary wedge pressure (r = 0.53, p = 0.0002). These findings indicate that adrenomedullin may play some important role in the pathophysiologic makeup of heart failure by its vasodilating effects against the concomitant exaggeration of humor pressor agents such as catecholamine and the renin-angiotensin system. Hemodynamic changes in pulmonary circulation may have some influence on the increased synthesis and secretion of plasma adrenomedullin in chronic congestive heart failure.

Adrenomedullin↗

Increased plasma adrenomedullin in acute myocardial infarction.

Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects (p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study (p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.

Adrenomedullin↗

Plasma adrenomedullin concentration in patients with heart failure.

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.

Adrenomedullin↗

The severity of residual coronary stenosis immediately after thrombolytic therapy does not influence the size of later left ventricular asynergic area.

To determine whether the severity of residual coronary artery stenosis immediately after thrombolytic therapy influences the size of later left ventricular (LV) asynergic area, we reviewed coronary angiograms (CAGs) and left ventriculograms (LVGs) of 31 patients with acute myocardial infarction (AMI). All patients received intracoronary urokinase therapy within 6 h after onset of AMI due to total occlusion of the proximal left anterior descending coronary artery (LAD). A dose of 960,000 IU urokinase was infused into the ostium of the left coronary artery over 40 min. Patients in whom antegrade blood flow without delayed distal filling was restored received rigorous anticoagulation. The patients were divided into three groups according to the severity of the coronary lesion immediately after urokinase therapy: 9 patients with complete occlusion in Group 1, 15 with > 90% stenosis in Group 2, and 7 with < 90% stenosis in Group 3. There were no significant differences in the baseline clinical characteristics among the patients in the three groups. The LADs in Group 1 were also totally occluded 1 month after urokinase therapy, the treated vessels in both Groups 2 and 3 were still patent, and patients in Group 2 showed a further reduction in residual stenosis. When LV asynergic area, regional wall motion, and global ejection fraction (EF) were compared among the three groups, no significant differences were demonstrated. In comparison with the data immediately after urokinase therapy, all parameters 1 month after therapy were significantly improved in both Groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Coronary angiographic ruptured atheromatous plaque as a predictor of future progression of stenosis.

To determine whether or not angiographic coronary morphology can predict future development/progression of narrowing, we reviewed coronary angiograms (CAGs) from 29 patients who underwent CAG studies twice but who had no myocardial revascularization during the period of the studies. The mean age of the patients was 52.9 +/- 8.5 years, and the mean interval between the studies was 25.4 +/- 22.6 months. Mean luminal diameter stenosis of 77 lesions that reduced the diameter by 50% or more on either CAG, but were not totally occluded on the initial CAG, increased from 62% to 79% (p less than 0.01). Progression of stenosis developed in 35 lesions (45%); the progression in 13 lesions of the 35 (37%) was on sites associated with no stenosis or mild stenosis on the initial CAG. No relation was found between the development/progression of stenosis and either its initial severity or elapsed time; however, the prevalence of the development/progression of stenosis was more frequent on sites with possible or probable ruptured atheromatous plaque on the initial CAG than on sites without such plaque (p less than 0.05). The evidence suggests that there is no apparent relation between the future development/progression of coronary narrowing and either the severity of stenosis on the initial CAG or elapsed time but that some of the development/progression can be predicted on the basis of certain specific coronary morphology.

Adult↗