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Biomedical subjects

K Miyatake

Publications and source records attributed to K Miyatake.

At least 37 records · Page 2Linked to original sources

Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.

We sought to assess the effects of oral supplementation of L-arginine, the precursor of nitric oxide (NO), on hemodynamics and exercise capacity in patients with pulmonary hypertension. Acute hemodynamic responses to oral L-arginine (0.5 g/10 kg body weight) or placebo were examined in 19 patients with primary or precapillary secondary pulmonary hypertension. Cardiopulmonary exercise tests were performed to measure peak oxygen consumption (peak V O(2)) and the ventilatory response to carbon dioxide production (V E-V CO(2) slope) before and 1 wk after treatment with L-arginine (1.5 g/10 kg body weight/d) or placebo. Oral supplementation of L-arginine significantly increased plasma L-citrulline, which indicated enhancement of NO production. Supplemental L-arginine produced a 9% decrease in mean pulmonary arterial pressure (53 +/- 4 to 48 +/- 4 mm Hg, p < 0.05) and a 16% decrease in pulmonary vascular resistance (14.8 +/- 1.5 to 12.4 +/- 1.4 Wood units, p < 0.05). L-arginine modestly decreased mean systemic arterial pressure (92 +/- 4 to 87 +/- 3 mm Hg, p < 0.05). A 1-wk supplementation of L-arginine resulted in a slight increase in peak V O(2) (831 +/- 88 to 896 +/- 92 ml/min, p < 0.05) and a significant decrease in the V E- V CO(2) slope (43 +/- 4 to 37 +/- 3, p < 0.05) without significant systemic hypotension. Hemodynamics and exercise capacity remained unchanged during placebo administration. These results suggest that oral supplementation of L-arginine may have beneficial effects on hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.

Administration, Oral↗

The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin.

The objective of this study was to investigate the stereoselective influence of bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese inpatients with heart disease. Thirty patients were administered a fixed-maintenance dose of warfarin alone once a day for at least 7 days. The other 25 patients were concomitantly administered warfarin and a 300 mg dose of bucolome once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after administration of bucolome. Serum concentration of warfarin enantiomers was measured by a chiral reversed-phase HPLC-ultraviolet detection method. The PT-INR was used as a measure of the pharmacodynamic effect of warfarin. Coadministration of bucolome and warfarin had no effect on serum (R)-warfarin concentration and significantly increased serum (S)-warfarin concentration compared with warfarin alone. The PT-INR of warfarin alone was significantly lower with bucolome cotreatment. These results indicate that the augmented anticoagulant effect of warfarin by bucolome is due to inhibition of (S)-warfarin metabolism in vivo. When bucolome is added to a stabilized regimen of warfarin therapy, the dose of warfarin should be reduced by about 30% to 60%, and caution should be exercised during the first 7 days after coadministration of bucolome.

Administration, Oral↗

Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure.

Ghrelin is a novel GH-releasing peptide that may also induce vasodilation and a positive energy balance through GH-independent mechanisms. However, the hemodynamic, renal, and hormonal effects of ghrelin in patients with chronic heart failure (CHF) remain unknown. Accordingly, 12 patients with CHF were given an iv infusion of human ghrelin (0.1 microg/kg.min) or placebo. Ghrelin significantly decreased mean arterial pressure (-9 mm Hg, P < 0.05) without a significant change in heart rate. Ghrelin significantly increased cardiac index (+25%, P < 0.05) and stroke volume index (+30%, P < 0.05), although it did not significantly alter mean pulmonary arterial pressure or pulmonary capillary wedge pressure. Infusion of ghrelin induced a marked increase in serum GH level (15-fold), associated with slight increases in circulating epinephrine, ACTH, cortisol, and PRL. Infusion of ghrelin did not significantly alter urine volume, urinary sodium excretion, or creatinine clearance. These hemodynamic, renal and hormonal parameters remained unchanged during placebo infusion. In summary, iv infusion of ghrelin, a potent GH-releasing peptide, had beneficial hemodynamic effects in patients with CHF in the absence of renal effects.

Aged↗

Serial assessment of left and right ventricular filling in patients with congestive heart failure.

Serial changes in the diastolic filling of both ventricles were studied using Doppler echocardiography in 19 patients with congestive heart failure from the acute to the convalescent stage. During the acute stage, left ventricular early filling velocity (E) was high (88 +/- 17 cm/s) and atrial filling velocity (A) was low (44 +/- 23 cm/s), whereas the right ventricular E was depressed (17 +/- 8 cm/s) and A was enhanced (40 +/- 9 cm/s). As the condition improved, left ventricular E decreased (43 +/- 11 cm/s, p < 0.01) and A increased (59 +/- 24 cm/s, p < 0.01) along with a decrease in the left ventricular and atrial dimensions. In contrast to the changes in left ventricular filling, right ventricular E increased (31 +/- 10 cm/s, p < 0.01) and A decreased (32 +/- 5 cm/s, p < 0.05). There are opposite directional changes in left and right ventricular filling with clinical improvement from the acute to the convalescent stage of congestive heart failure, which suggest that the changes are related to improvement of the hemodynamic conditions of both ventricles. The changes in the right ventricular filling pattern was likely to be related to changes in right ventricular afterload, ventricular interaction and external constraint rather than a change in right ventricular filling pressure.

Adult↗

Comparative left ventricular functional and neurohumoral effects of chronic treatment with carvedilol versus metoprolol in patients with dilated cardiomyopathy.

The efficacy of treating dilated cardiomyopathy with metoprolol was compared with that of carvedilol. Metoprolol was administered to 29 patients, and carvedilol to 62. Patients who could not be dosed with up to 40 mg daily of metoprolol or 20 mg daily of carvedilol were defined as intolerant. As well as the tolerability of these beta-blockers, the effects on left ventricular end-diastolic dimension (LVDd), fractional shortening (FS), plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations, the delayed heart and mediastinum (H/M) ratio determined from metaiodobenzylguanidine imaging were compared. Drug intolerance occurred in 24% of patients in the metoprolol group and 19% in the carvedilol group. Among the drug-tolerant patients, LVDd, FS and plasma BNP concentration improved in both groups and to the same degree. Only 25% of drug-tolerant patients in the metoprolol group had a delayed H/M ratio below 1.9 compared with 57% in the carvedilol group. Both metoprolol and carvedilol, when tolerated, improve cardiac function and neurohumoral factors to the same degree. However, carvedilol is preferable to metoprolol for patients with a low delayed H/M ratio.

3-Iodobenzylguanidine↗

Expression of a gene encoding chitinase (pCA 8 ORF) from Aeromonas sp. no. 10S-24 in Escherichia coli and enzyme characterization.

A gene encoding chitinase from Aeromonas sp. no. 10S-24 was expressed using pTrc99A in Escherichia coli JM 105 which yielded a 5-fold higher activity than when pUC19 was used. Three different truncated enzymes (SA-1, SA-2 and SA-3) were obtained after purification. Their isoelectric points were 7.0, 6.9, and 6.7, respectively. The enzymes showed two optimum pHs, 4.0 and 7.0, when incubated with ethylene glycol chitin as the substrate, and were stable over a wide pH range (3.0-9.0). The optimum temperature was 60 degrees C and the enzymes were stable up to 50 degrees C. The chitinases exhibited wide substrate specificities for chitin-related compounds.

Journal Article↗

A new model-based method of reconstructing central aortic pressure from peripheral arterial pressure.

We have shown in our previous study that the transfer function between central aortic pressure and tonometric radial arterial pressure can be modeled as a pure elastic lossless tube terminated with a modified Windkessel. We hypothesized, using the model-derived radial arterial flow, that central pressure could be reconstructed by adding the time-shifted forward and backward pressure components (Stergiopulos et al.: Am J Physiol 274: H1386---H1392, 1998). In eight patients (age 16--75), central micromanometric and radial arterial tonometric pressure were measured simultaneously. We imposed measured tonometric pressure to the terminal modified Windkessel to estimate radial arterial flow, with which tonometric pressure was separated into forward and backward components. These components were then appropriately time shifted, and summed to central pressure. We used average parameter values for the terminal impedance, but individualized the transmission delay. The poor correlation (r(2)) between tonometric and central pressure (0.264--0.765) was improved by both central pressure reconstruction methods (generalized transfer function: 0.887--0.974, model-based method: 0.849--0.979). The sensitivity analysis indicated that the key model parameter in reconstructing central pressure was the transmission delay. We conclude that our model-based method was capable of reconstructing central pressure as precisely as the generalized transfer function method, and also capable of individualizing the transfer function by changing the transmission delay.

Aorta↗

[Clinical validation of accuracy of anatomical M-mode measurements: effect of harmonic imaging].

OBJECTIVES: Recent advances in ultrasound technology allow reconstruction of images from stored radiofrequency information and creating of M-mode echocardiograms along an M-mode cursor of any direction (anatomical M-mode echocardiography). METHODS: The accuracy of the measurements obtained by anatomical M-mode echocardiography was evaluated by comparing the measurements with those by B-mode echocardiography with or without harmonic imaging in 8 normal subjects and 14 patients with cardiac disorders. Measurements used the left ventricular short-axis image in 4 different directions (0 to 6, 3 to 9, 1 to 7 and 5 to 11 o'clock). RESULTS: Anatomical M-mode and B-mode measurements showed good linear relationships with correlation coefficients of 0.90 to 0.99 in any of the 4 directions. However, measurements in the lateral direction (3 to 9 o'clock) showed larger errors than those in the other directions (p < 0.05). With the use of harmonic imaging, the errors tended to become smaller, although it did not reach statistical significance. CONCLUSIONS: Anatomical M-mode echocardiography accurately measures the left ventricular internal diameter in any direction except the lateral direction. Harmonic imaging is useful to decrease the errors.

Aged↗

[Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension].

BACKGROUND: Plasma brain natriuretic peptide (BNP) level increases in proportion to the degree of right ventricular dysfunction in pulmonary hypertension. We sought to assess the prognostic significance of plasma BNP in patients with primary pulmonary hypertension. METHODS AND RESULTS: Plasma BNP was measured in 60 patients with primary pulmonary hypertension at diagnostic catheterization, together with atrial natriuretic peptide, norepinephrine, and epinephrine. Measurements were repeated in 53 patients after a mean follow-up period of 3 months. Forty-nine of the patients received intravenous or oral prostacyclin. During a mean follow-up period of 24 months, 18 patients died of cardiopulmonary causes. According to multivariate analysis, baseline plasma BNP was an independent predictor of mortality. Patients with a supramedian level of baseline BNP (> or = 150 pg/ml) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves (p < 0.05). Plasma BNP in survivors decreased significantly during the follow-up (217 +/- 38 to 149 +/- 30 pg/ml, p < 0.05), whereas that in nonsurvivors increased (365 +/- 77 to 544 +/- 68 pg/ml, p < 0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (> or = 180 pg/ml) than for those with an inframedian value (p < 0.0001). CONCLUSIONS: A high level of plasma BNP, and in particular, a further increase in plasma BNP during follow-up, may have a strong, independent association with increased mortality in patients with primary pulmonary hypertension.

Biomarkers↗

[Clinical significance of measuring inferior vena cava dimension in patients with acute exacerbation of chronic heart failure].

OBJECTIVES: This study determined the clinical significance of measuring the inferior vena cava dimension in patients with heart failure. METHODS: The subjects were 373 patients admitted due to acute exacerbation of chronic heart failure. The relationships were examined between inferior vena cava dimension in the end-expiratory phase on admission and in the stable state and etiology of heart failure, age, New York Heart Association (NYHA) functional classification in the stable state (before exacerbation), body weight, grade of tricuspid regurgitation, left ventricular end-diastolic dimension and left ventricular ejection fraction measured by two-dimensional echocardiography in the stable state and on admission, severity of lung congestion (Killip's classification) on admission, and clinical course during treatment. RESULTS: The inferior vena cava dimension was not correlated with etiology, age, NYHA functional classification, body weight, left ventricular end-diastolic dimension or left ventricular ejection fraction, but was correlated with the grade of tricuspid regurgitation (r = 0.78, p < 0.0001 in the stable state, r = 0.60, p < 0.0001 and on admission). The severity of lung congestion did not correlate with inferior vena cava dimension on admission or the increase in inferior vena cava dimension. The increase in body weight on admission was correlated with the increase in inferior vena cava dimension (r = 0.83, p < 0.0001), but did not correlate with inferior vena cava dimension on admission. Tricuspid regurgitation grade and inferior vena cava dimension were restored to the stable state when body weight reached stable state after treatment in patients (n = 202) with inferior vena cava dimension increased by over 5 mm on admission. CONCLUSIONS: Inferior vena cava dimension in patients with heart failure is correlated with the tricuspid regurgitation grade in the stable state and at acute exacerbation. The increase in inferior vena cava dimension between stable and exacerbated states, but not the actual value, is clinically useful to evaluate patients with acute exacerbation of chronic heart failure.

Chronic Disease↗

Clinical analysis of myocardial perfusion and metabolism in patients with hypertrophic cardiomyopathy by single photon emission tomography and positron emission tomography.

BACKGROUND AND OBJECTIVES: Changes in myocardial energy metabolism and their relation to coronary flow reserve in hypertrophic cardiomyopathy were assessed by myocardial fatty acid imaging with iodine-123 beta-methyliodophenyl pentadecanoic acid single photon emission tomography (123I-BMIPP SPECT) (fasting), glucose imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) (fasting), and perfusion imaging with nitrogen-13 (13N)-ammonia PET (dipyridamole-stress and at rest) in adult patients with hypertrophic cardiomyopathy and with asymmetric septal hypertrophy. RESULTS: 123I-BMIPP defects mismatched with thallium-201 (201Tl) uptake were often observed in the hypertrophic septal regions indicating reduced fatty acid utilization incidence of 59% (22/37). 18F-FDG images showed diffusely increased uptake in most of the patients (73%, 27/37), but showed regionally increased 18F-FDG uptake at the septal regions in only two patients. Study of 18 hypertrophic cardiomyopathy patients with the mismatched 123I-BMIPP defects found that the severity of the defects correlated with reduced coronary flow reserve determined by the 13N-ammonia PET study. On the other hand, changes in 18F-FDG images were not related to those in coronary flow reserve. CONCLUSIONS: These results suggest that the mismatched 123I-BMIPP defects, which indicate abnormality in myocardial fatty acid metabolism, occur under reduced coronary flow reserve, and may contribute to the prediction of progressive myocardial failure in patients with hypertrophic cardiomyopathy. The significance of 18F-FDG in patients with hypertrophic cardiomyopathy is still uncertain.

Adult↗

Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonary hypertension in rats.

BACKGROUND: Prostacyclin is a potent vasodilator that also inhibits platelet adhesion and cell growth. We investigated whether in vivo gene transfer of human prostacyclin synthase (PGIS) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. METHODS AND RESULTS: The cDNA encoding PGIS was intratracheally transfected into the lungs of rats by the hemagglutinating virus of Japan-liposome method. Rats transfected with control vector lacking the PGIS gene served as controls. Three weeks after MCT injection, mean pulmonary arterial pressure and total pulmonary resistance had increased significantly; the increases were significantly attenuated in PGIS gene-transfected rats compared with controls [mean pulmonary arterial pressure, 31+/-1 versus 35+/-1 mm Hg (-12%); total pulmonary resistance, 0.087+/-0.01 versus 0.113+/-0.01 mm Hg x mL x min(-1) x kg(-1) (-23%), both P:<0.05]. Systemic arterial pressure and heart rate were unaffected. Histologically, PGIS gene transfer inhibited the increase in medial wall thickness of peripheral pulmonary arteries that resulted from MCT injection. PGIS immunoreactivity was intense predominantly in the bronchial epithelium and alveolar cells. Lung tissue levels of 6-keto-PGF(1alpha), a stable metabolite of prostacyclin, were significantly increased for >/=1 week after transfer of PGIS gene. The Kaplan-Meier survival curves demonstrated that repeated transfer of PGIS gene every 2 weeks increased survival rate in MCT rats (log-rank test, P:<0.01). CONCLUSIONS: Intratracheal transfer of the human PGIS gene augmented pulmonary prostacyclin synthesis, ameliorated MCT-induced pulmonary hypertension, and thereby improved survival in MCT rats.

6-Ketoprostaglandin F1 alpha↗

Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension.

BACKGROUND: Plasma brain natriuretic peptide (BNP) level increases in proportion to the degree of right ventricular dysfunction in pulmonary hypertension. We sought to assess the prognostic significance of plasma BNP in patients with primary pulmonary hypertension (PPH). METHODS AND RESULTS: Plasma BNP was measured in 60 patients with PPH at diagnostic catheterization, together with atrial natriuretic peptide, norepinephrine, and epinephrine. Measurements were repeated in 53 patients after a mean follow-up period of 3 months. Forty-nine of the patients received intravenous or oral prostacyclin. During a mean follow-up period of 24 months, 18 patients died of cardiopulmonary causes. According to multivariate analysis, baseline plasma BNP was an independent predictor of mortality. Patients with a supramedian level of baseline BNP (>/=150 pg/mL) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves (P<0.05). Plasma BNP in survivors decreased significantly during the follow-up (217+/-38 to 149+/-30 pg/mL, P<0. 05), whereas that in nonsurvivors increased (365+/-77 to 544+/-68 pg/mL, P<0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (>/=180 pg/mL) than for those with an inframedian value (P<0.0001). CONCLUSIONS: A high level of plasma BNP, and in particular, a further increase in plasma BNP during follow-up, may have a strong, independent association with increased mortality rates in patients with PPH.

Adolescent↗

Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure.

BACKGROUND: Experimental studies have shown that adrenomedullin (AM) causes vasodilatation, diuresis, and a positive inotropic effect. In humans, however, whether infusion of AM has beneficial effects in congestive heart failure (CHF) remains unknown. METHODS AND RESULTS: Hemodynamic, renal, and hormonal responses to intravenous infusion of human AM (0.05 microg. kg(-1). min(-1)) were examined in 7 patients with CHF and 7 normal healthy subjects (NL). In NL group, AM significantly decreased mean arterial pressure (-16 mm Hg, P<0. 05) and increased heart rate (+12 bpm, P<0.05). In CHF group, AM also decreased mean arterial pressure (-8 mm Hg, P<0.05) and increased heart rate (+5 bpm, P<0.05), but to a much lesser degree (P<0.05 versus NL). AM markedly increased cardiac index (CHF, +49%; NL, +39%, P<0.05) while decreasing pulmonary capillary wedge pressure (CHF, -4 mm Hg; NL, -2 mm Hg, P<0.05). AM significantly decreased mean pulmonary arterial pressure only in CHF (-4 mm Hg, P<0.05). AM increased urine volume (CHF, +48%; NL, +62%, P<0.05) and urinary sodium excretion (CHF, +42%; NL, +75%, P<0.05). Only in CHF, plasma aldosterone significantly decreased during (-28%, P<0.05) and after (-36%, P<0.05) AM infusion. These parameters remained unchanged in 7 patients with CHF and 6 healthy subjects who received placebo. CONCLUSIONS: Intravenous infusion of AM has beneficial hemodynamic and renal effects in patients with CHF.

Adrenomedullin↗