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Heart (British Cardiac Society) 01/2005; 90(12):1485-6. · 4.22 Impact Factor
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T Noda,
H Takaki,
T Kurita,
K Suyama, N Nagaya,
A Taguchi,
N Aihara,
S Kamakura,
K Sunagawa,
K Nakamura,
T Ohe,
M Horie,
C Napolitano,
J A Towbin,
S G Priori,
W Shimizu
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ABSTRACT: Differences in the sensitivity of the genotype of the congenital long QT syndrome to sympathetic stimulation have been suggested. This study compared the influence of sympathetic stimulation on continuous corrected QT (QTc) intervals between LQT1, LQT2 and LQT3 forms of the congenital long QT syndrome.
We recorded a 12-lead electrocardiogram continuously before and after bolus injection (0.1 microg x kg(-1)) of epinephrine followed by continuous infusion (0.1 microg x kg(-1) min(-1)) in 12 LQT1, 10 LQT2, 6 LQT3, and 13 control patients. The QT intervals and previous RR intervals of all beats were measured semi-automatically, and the QTc intervals of all beats were calculated by Bazett's method. The dynamic response of the RR interval to epinephrine was no different between the four groups. The QTc was prolonged remarkably (477+/-42 to 631+/- 59 ms; P<0.0005, % delta prolongation =+32%) as the RR was maximally decreased (at peak of epinephrine), and remained prolonged at steady state conditions of epinephrine (556+/-56 ms; P<0.0005 vs baseline, +17%) in LQT1 patients. Epinephrine also prolonged the QTc dramatically (502+/-23 to 620+/-39 ms; P<0.0005, +24%) at peak of epinephrine in LQT2 patients, but this shortened to baseline levels at steady state (531+/-25 ms; P=ns vs baseline, +6%). The QTc was much less prolonged at peak of epinephrine in LQT3 (478+/-44 to 532+/-41 ms; P<0.05, +11%) and controls (394+/-21 to 456+/-18 ms; P<0.0005, +16%) than in LQT1 and LQT2 patients, and shortened to the baseline levels (LQT3; 466+/-49 ms, -3%, controls; 397+/-16 ms, +1%; P=ns vs baseline) at steady state.
Our data suggest that the dynamic response of ventricular repolarization to sympathetic stimulation differs between LQT1, LQT2 and LQT3 syndromes, and may explain why the trigger of cardiac events differs between the genotypes.
European Heart Journal 06/2002; 23(12):975-83. · 10.48 Impact Factor
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ABSTRACT: To investigate the effect of beraprost sodium, an orally active prostacyclin analogue, on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension.
Symptom limited cardiopulmonary exercise testing was performed before and 3 (1) months (mean (SEM)) after beraprost treatment in 30 patients with precapillary pulmonary hypertension (14 with primary pulmonary hypertension and 16 with chronic thromboembolic pulmonary hypertension).
Long term treatment with beraprost resulted in significant increases (mean (SEM)) in peak workload (87 (4) W to 97 (5) W, p < 0.001) and peak oxygen consumption (peak VO2, 14.9 (0.7) ml/kg/min to 16.8 (0.7) ml/kg/min, p < 0.001). Beraprost decreased the ventilatory response to carbon dioxide production during exercise (VE-VCO2 slope, 42 (2) to 37 (1), p < 0.001). No significant difference in the responses of these variables to beraprost treatment was observed between patients with primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension.
Oral administration of beraprost sodium may improve exercise capacity and ventilatory efficiency in patients with both primary and chronic thromboembolic pulmonary hypertension.
Heart (British Cardiac Society) 04/2002; 87(4):340-5. · 4.22 Impact Factor
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ABSTRACT: Although it has been reported that the circulating adrenomedullin (AM) level is elevated in hypertension and renal failure, the pathophysiological significance of circulating and intrarenal AM in malignant hypertension remains unknown. We investigated the circulating and intrarenal AM system in rats with malignant hypertension by measuring the plasma level, renal tissue level, and mRNA abundance of AM and the mRNA abundance of AM receptor. We also investigated the effects of intravenously infused calcitonin gene-related peptide (CGRP)-(8-37), an antagonist of AM, on the hemodynamics and renal tubular function. We studied the following four groups: control Wistar-Kyoto rats (WKY), control spontaneously hypertensive rats (C-SHR), salt-loaded SHR (S-SHR), and DOCA-salt SHR (D-SHR). After 3 wk of DOCA treatment, D-SHR developed malignant hypertension. D-SHR were characterized by higher blood pressure, kidney weight, urinary protein excretion and blood urea nitrogen, and lower creatinine clearance compared with the other three groups. The plasma AM level and urinary excretion of AM were markedly higher in D-SHR than in the other three groups. In the kidney, the tissue AM level and the expression of AM mRNA in the renal medulla were significantly increased in D-SHR compared with the other three groups, whereas there were no significant differences in these levels in the renal cortex among the four groups. In the renal AM receptor system, the expression of the gene for receptor activity modifying protein 3 was significantly increased in the renal medulla in D-SHR compared with the other three groups. An immunohistochemical study revealed that AM immunostaining in renal collecting duct cells and distal tubules was more intense in D-SHR than in the other three groups. After CGRP-(8-37) infusion, blood pressure increased significantly and urinary sodium excretion and urine flow decreased significantly only in D-SHR. These results suggest that the increased circulating AM and renal AM and the increased expression of the mRNA for AM and its receptor may at least partly compensate for the malignant hypertensive state in certain forms of malignant hypertension via the hypotensive, natriuretic, and diuretic actions of AM.
AJP Regulatory Integrative and Comparative Physiology 01/2002; 281(6):R2079-87. · 3.34 Impact Factor
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ABSTRACT: 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.
Journal of Clinical Endocrinology & Metabolism 12/2001; 86(12):5854-9. · 6.50 Impact Factor
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N Nagaya,
M Uematsu,
M Kojima,
Y Date,
M Nakazato,
H Okumura,
H Hosoda,
W Shimizu,
M Yamagishi,
H Oya,
H Koh,
C Yutani,
K Kangawa
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ABSTRACT: Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, that may also cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in the cachexia associated with chronic heart failure (CHF).
Plasma ghrelin was measured in 74 patients with CHF and 12 control subjects, together with potentially important anabolic and catabolic factors, such as GH and tumor necrosis factor (TNF-alpha). Patients with CHF were divided into two groups, those with cachexia (n=28) and those without cachexia (n=46). Plasma ghrelin did not significantly differ between all CHF patients and controls (181+/-10 versus 140+/-14 fmol/mL, P=NS). However, plasma ghrelin was significantly higher in CHF patients with cachexia than in those without cachexia (237+/-18 versus 147+/-10 fmol/mL, P<0.001). Circulating GH, TNF-alpha, norepinephrine, and angiotensin II were also significantly higher in CHF patients with cachexia than in those without cachexia. Interestingly, plasma ghrelin correlated positively with GH (r=0.28, P<0.05) and TNF-alpha (r=0.31, P<0.05) and negatively with body mass index (r=-0.35, P<0.01).
Plasma ghrelin was elevated in cachectic patients with CHF, associated with increases in GH and TNF-alpha and a decrease in body mass index. Considering ghrelin-induced positive energy effects, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with CHF.
Circulation 11/2001; 104(17):2034-8. · 14.74 Impact Factor
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T Iwase, N Nagaya,
M Ando,
T Satoh,
F Sakamaki,
S Kyotani,
H Takaki,
Y Goto,
Y Ohkita,
M Uematsu,
N Nakanishi,
K Miyatake
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ABSTRACT: To assess acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Cardiopulmonary exercise testing was performed in 20 patients with CTEPH before thromboendarterectomy (baseline), one month after (early phase), and four months after (late phase). Peak oxygen uptake (peak VO(2)) and the ventilatory response to carbon dioxide production (VE-VCO(2) slope) were measured for assessment of exercise capacity and ventilatory efficiency. Right heart catheterisation was performed in all patients before and one month after surgery.
Baseline peak VO(2) decreased and VE-VCO(2) slope increased along with the increase in pulmonary vascular resistance in patients with CTEPH. After thromboendarterectomy, the VE-VCO(2) slope decreased greatly from baseline to the early phase (mean (SD), 50 (9) to 37 (7), p < 0.05) and reached a steady level thereafter. In contrast, a continued increase in peak VO(2) was noted from the early to the late phase (16.9 (4.1) to 21.1 (5.0) ml/kg/min, p < 0.05). The decrease in the VE-VCO(2) slope from baseline to the early phase, but not the increase in peak VO(2), correlated strongly with the decrease in pulmonary vascular resistance after surgery (r = 0.75, p < 0.01).
Thromboendarterectomy may cause an immediate improvement in ventilatory efficiency, possibly through its beneficial haemodynamic effects. In contrast, exercise capacity may continue to improve towards the late phase, reflecting peripheral adaptation to exercise.
Heart (British Cardiac Society) 09/2001; 86(2):188-92. · 4.22 Impact Factor
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N Nagaya,
M Uematsu,
M Kojima,
Y Ikeda,
F Yoshihara,
W Shimizu,
H Hosoda,
Y Hirota,
H Ishida,
H Mori,
K Kangawa
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ABSTRACT: Ghrelin is a novel growth hormone (GH)-releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF).
Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 microg/kg SC BID) or saline was administered for 3 weeks. Echocardiography and cardiac catheterization were performed. Serum GH and insulin-like growth factor-1 were significantly higher in both CHF and sham rats treated with ghrelin than in those given placebo (P<0.05 for both). CHF rats given placebo showed an impaired increase in body weight compared with sham rats given placebo (P<0.05). CHF rats treated with ghrelin, however, showed a significantly greater increase in body weight than those given placebo (+10% versus +3%, P<0.05). They showed significantly higher cardiac output (315+/-49 versus 266+/-31 mL. min(-1). kg(-1), P<0.05) and LV dP/dt(max) (5738+/-908 versus 4363+/-973 mm Hg/s, P<0.05) than CHF rats given placebo. Ghrelin increased diastolic thickness of the noninfarcted posterior wall, inhibited LV enlargement, and increased LV fractional shortening in CHF rats (from 15+/-3% to 19+/-3%, P<0.05).
Chronic subcutaneous administration of ghrelin improved LV dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with CHF.
Circulation 09/2001; 104(12):1430-5. · 14.74 Impact Factor
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ABSTRACT: The purpose of this investigation was to differentiate chronic pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by means of the indexes of pulmonary arterial reflection.
These differences in the primary lesions would make pulmonary artery reflection occur earlier in CPTE than in PPH. Although the analysis of pulsatility of pulmonary arterial pressure is useful in the differential diagnosis of PPH and CPTE, it is not known whether the analysis of pulmonary artery reflection can differentiate CPTE from PPH.
Since CPTE predominantly involves the proximal arteries, whereas PPH involve the peripheral arteries, we hypothesized that patients with CPTE have a large augmentation index and a short inflection time. For this study, we enrolled 62 patients who had CPTE (31 patients) and PPH (31 patients). We measured pulmonary arterial pressure using a fluid filled system that included a balloon-tipped flow directed catheter. To quantify the pulmonary artery reflection, we used the augmentation index and inflection time.
The augmentation index was markedly higher in CPTE than it was in PPH (27.4% +/- 15.2% [SD] and -25.1% +/- 26.9%, respectively, p < 0.001) and was diagnostic in separating the two groups. Inflection time separated the two groups reasonably well (97 +/- 20 ms and 210 +/- 49 ms, respectively, p < 0.001).
The analysis of pulmonary arterial reflection is useful in the differential diagnosis of CPTE and PPH.
Journal of the American College of Cardiology 08/2001; 38(1):214-8. · 14.16 Impact Factor
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ABSTRACT: Through our investigations of the intact pulmonary circulation, we aimed to find out whether K(ATP) channels contribute to regulating basal vascular tone and to clarify which vascular segments dilate during K(ATP) channel activation under basal tone conditions. Using an X-ray television system on anesthetized cat lungs, we measured internal diameter (ID) responses to two K(ATP) channel inhibitors (glibenclamide and 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl-hydrochloride (U-37883A)) and to an activator (levcromakalim) in normoxic pulmonary arteries. In conduit arteries (800-3000 microm ID), the inhibitors and activator induced larger ID constrictions (14-17%) and dilatations (29-32%), respectively. However, in resistance arteries (<500 microm), the constriction response was negligible and the dilatation response relatively small (5-10%). The data suggest that K(ATP) channels are active and capable of regulating basal vascular tone primarily within conduit pulmonary arteries even though these channels are present in all pulmonary arteries.
European Journal of Pharmacology 06/2001; 422(1-3):181-4. · 2.52 Impact Factor
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ABSTRACT: To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin (10 microg/kg) or placebo and vice versa 1-2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH (15-fold). The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure (-12 mmHg, P < 0.05) without a significant change in heart rate (-4 beats/min, P = 0.39). Ghrelin significantly increased cardiac index (+16%, P < 0.05) and stroke volume index (+22%, P < 0.05). We also examined ghrelin receptor [GH secretagogues receptor (GHS-R)] gene expression in the aortas, the left ventricles, and the left atria of rats by RT-PCR. GHS-R mRNA was detectable in the rat aortas, left ventricles, and left atria, suggesting that ghrelin may cause cardiovascular effects through GH-independent mechanisms. In summary, human ghrelin elicited a potent, long-lasting GH release and had beneficial hemodynamic effects via reducing cardiac afterload and increasing cardiac output without an increase in heart rate.
AJP Regulatory Integrative and Comparative Physiology 06/2001; 280(5):R1483-7. · 3.34 Impact Factor
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S Miyamoto,
Y Goto,
M Fujita,
S Daikoku, N Nagaya,
S Yasuda,
H Sumida,
I Morii,
A Itoh,
S Miyazaki,
H Nonogi
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ABSTRACT: The TAMI-6 trial has demonstrated that coronary reperfusion >6h after onset (ie, late reperfusion) in patients with acute myocardial infarction (AMI) does not improve left ventricular (LV) function during the chronic phase of infarction. However, the low patency rate (only 60%) of the infarct-related artery (IRA) during the chronic phase in the TAMI-6 trial raises a new hypothesis that late reperfusion with a higher patency rate may improve LV function during the chronic phase. Forty-four patients with AMI, who were admitted to hospital 6-24h after the symptom onset and in whom emergency coronary angiography revealed a total occlusion of the IRA, were randomly assigned to either the late reperfusion group (n=22) or the non-reperfusion group (n=22). The initial success rate of reperfusion therapy in the late reperfusion group was 86% and the chronic patency rate of the IRA was 91%. The improvements in ejection fraction and chord shortening in the infarct region from the acute phase to the chronic phase were significantly greater in the late reperfusion group than in the non-reperfusion group. Late reperfusion with a high patency rate of the IRA significantly improves LV global and regional function in patients with AMI.
Japanese Circulation Journal 06/2001; 65(5):389-94.
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Y Tanabe,
M Inagaki,
T Kurita, N Nagaya,
A Taguchi,
K Suyama,
N Aihara,
S Kamakura,
K Sunagawa,
K Nakamura,
T Ohe,
J A Towbin,
S G Priori,
W Shimizu
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ABSTRACT: The study compared the influence of sympathetic stimulation on transmural and spatial dispersion of repolarization between LQT1 and LQT2 forms of congenital long QT sYndrome (LQTS).
Cardiac events are more associated with sympathetic stimulation in LQT1 than in LQT2 or LQT3 syndrome. Experimental studies have suggested that the interval between Tpeak and Tend (Tp-e) in the electrocardiogram (ECG) reflects transmural dispersion of repolarization across the ventricular wall.
We recorded 87-lead body-surface ECGs before and after epinephrine infusion (0.1 microg/kg/min) in 13 LQT1, 6 LQT2, and 7 control patients. The Q-Tend (QT-e), Q-Tpeak (QT-p), and Tp-e were measured automatically from 87-lead ECGs, corrected by Bazett's method (QTc-e, QTc-p, Tcp-e), and averaged among all 87-leads and among 24-leads, which reflect the potential from the left ventricular free wall. As an index of spatial dispersion of repolarization, the dispersion of QTc-e (QTc-eD) and QTc-p (QTc-pD) were obtained among 87-leads and among 24-leads, and were defined as the interval between the maximum and the minimum of the QTc-e and the QTc-p, respectively.
Epinephrine significantly increased the mean QTc-e but not the mean QTc-p, resulting in a significant increase in the mean Tcp-e in both LQT1 and LQT2, but not in control patients. The epinephrine-induced increases in the mean QTc-e and Tcp-e were larger in LQT1 than in LQT2, and were more pronounced when the averaged data were obtained from 24-leads than from 87-leads. Epinephrine increased the maximum QTc-e but not the minimum QTc-e, producing a significant increase in the QTc-eD in both LQT1 and LQT2 patients, but not in control patients. The increase in the QTc-eD was larger in LQT1 than in LQT2 patients.
Our data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation.
Journal of the American College of Cardiology 04/2001; 37(3):911-9. · 14.16 Impact Factor
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ABSTRACT: 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.
American Journal of Respiratory and Critical Care Medicine 03/2001; 163(4):887-91. · 11.08 Impact Factor
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N Nagaya,
T Nishikimi,
M Uematsu,
T Satoh,
S Kyotani,
F Sakamaki,
M Kakishita,
K Fukushima,
Y Okano,
N Nakanishi,
K Miyatake,
K Kangawa
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ABSTRACT: 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.
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).
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.
Journal of Cardiology 02/2001; 37(2):110-1. · 1.28 Impact Factor
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ABSTRACT: Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis. We measured the plasma levels of AM-m and total AM (AM-T; AM-m+AM-Gly) using a recently developed specific immunoradiometric assay, and thus calculated plasma AM-Gly levels, in blood samples obtained from the femoral vein, pulmonary artery, left atrium and aorta of 28 consecutive patients with mitral stenosis (20 females and eight males; age 53+/-10 years). Patients with mitral stenosis had significantly higher venous concentrations of AM-T, AM-Gly and AM-m than age-matched normal controls (AM-T, 15.9+/-2.5 and 10.6+/-2.1 pmol/l respectively; AM-Gly, 14.0+/-2.1 and 9.8+/-1.9 pmol/l respectively; AM-m, 1.9+/-0.6 and 1.1+/-0.3 pmol/l respectively; each P<0.001). There was a significant decrease in the concentrations of AM-m and AM-T between the pulmonary artery and the left atrium (AM-T, 16.1+/-2.7 and 14.0+/-2.4 pmol/l respectively; AM-m, 2.0+/-0.6 and 0.7+/-0.2 pmol/l respectively; each P<0.001); however, there were no differences in plasma AM-Gly levels between the pulmonary artery and the left atrium (14.1+/-2.3 and 13.5+/-2.3 pmol/l respectively). The venous concentrations of AM-m, AM-Gly and AM-T showed similar correlations with mean pulmonary artery pressure (AM-T, r=0.67; AM-Gly, r=0.63; AM-m, r=0.59; each P<0.001) and total pulmonary vascular resistance (AM-T, r=0.77; AM-Gly, r=0.70; AM-m, r=0.75; each P<0.001). These results suggest that the plasma concentration of AM-m is increased in parallel with those of AM-Gly and AM-T, and that the main site for clearance of AM-m from the plasma is the lung; the extracted AM-m in the lungs may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.
Clinical Science 01/2001; 100(1):61-6. · 4.61 Impact Factor
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ABSTRACT: Pulmonary hypertension (PH) is a serious and often fatal complication of systemic lupus erythematosus (SLE). Several potential mechanisms have been postulated for narrowing of vessels as a result of pulmonary vasculitis and pulmonary thromboembolism caused by antiphospholipid antibodies. Pulmonary thromboendarterectomy for chronic pulmonary thromboembolism is performed to alleviate pulmonary hypertension. We report three rare cases of SLE with antiphospholipid syndrome in patients who presented with PH secondary to chronic pulmonary thromboembolism. Pulmonary thromboendarterectomy was performed, and all patients remained well without deterioration of PH after surgery. Pulmonary thromboendarterectomy should be considered as an effective method of treatment for this disease.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 01/2001; 38(12):958-64.
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ABSTRACT: In the present study we investigated the form of expression, action, second messenger, and the cellular location of urocortin, a member of the corticotropin-releasing factor (CRF) family, in the heart. Urocortin mRNA, as shown by quantitative RT-PCR analysis, is expressed in the cultured rat cardiac nonmyocytes (NMC) as well as myocytes (MC) in the heart, whereas CRF receptor type 2beta (CRF-R2beta), presumed urocortin receptor mRNA, is predominantly expressed in MC compared with NMC. Urocortin mRNA expression is higher in left ventricular (LV) hypertrophy than in normal LV, whereas CRF-R2beta mRNA expression is markedly depressed in LV hypertrophy compared with normal LV. Urocortin more potently increased the cAMP levels in both MC and NMC than did CRF, and its effect was more potent in MC than in NMC. Urocortin significantly increased protein synthesis by [(14)C]Phe incorporations and atrial natriuretic peptide secretion in MC and collagen and increased DNA synthesis by [(3)H]prolin and [(3)H]Thy incorporations in NMC. An immunohistochemical study revealed that urocortin immunoreactivity was observed in MC in the normal human heart and that it was more intense in the MC of the human failing heart than in MC of the normal heart. These results, together with the recent evidence of urocortin for positive inotropic action, suggest that increased urocortin in the diseased heart may modulate the pathophysiology of cardiac hypertrophy or failing heart, at least in part, via cAMP signaling pathway.
AJP Heart and Circulatory Physiology 01/2001; 279(6):H3031-9. · 3.71 Impact Factor
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ABSTRACT: Thrombosis in situ related to endothelial cell injury may contribute to the development of pulmonary hypertension (PH). P-selectin, a leukocyte adhesion receptor present in endothelial cells and platelets, reflects endothelial injury and platelet activation, and thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium.
To assess abnormal coagulation due to endothelial injury in patients with PH, plasma levels of soluble P-selectin and TM were measured in 32 patients with primary PH (PPH), 25 with secondary pulmonary arterial hypertension (sPAH), 31 with pulmonary venous hypertension (PVH), and 17 healthy subjects (Control). These measurements were repeated after continuous infusion of prostacyclin in 15 patients with PPH and 3 with sPAH. P-selectin levels in both the sPAH and PPH groups were significantly higher than those in the Control and PVH groups (P<0.05). Plasma TM level in the PPH group was significantly lower than those in the other groups (P<0.01). After prostacyclin therapy, the lower TM level was increased and the higher P-selectin level was decreased (P<0.05).
Decreased TM and increased P-selectin in PPH and sPAH may reflect in situ thrombosis due to endothelial injury. Prostacyclin may act not only as a vasodilator but also as an agent that improves endothelial injury and altered hemostasis in pulmonary arterial injury.
Circulation 12/2000; 102(22):2720-5. · 14.74 Impact Factor
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N Nagaya,
T Nishikimi,
M Uematsu,
T Satoh,
H Oya,
S Kyotani,
F Sakamaki,
K Ueno,
N Nakanishi,
K Miyatake,
K Kangawa
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ABSTRACT: To investigate whether infusion of adrenomedullin, a potent vasorelaxant peptide, has beneficial haemodynamic and hormonal effects in patients with pulmonary hypertension.
The haemodynamic and hormonal responses to intravenous infusion of adrenomedullin (0.05 microgram/kg/min) or placebo were examined in 13 patients with precapillary pulmonary hypertension.
Infusion of adrenomedullin produced a 44% increase in cardiac index (mean (SD) 1.8 (0.2) to 2.6 (0.3) l/min/m(2), p < 0. 05) and a 32% decrease in pulmonary vascular resistance (19.7 (1.4) to 13.4 (1.3) units, p < 0.05), with a 4% reduction in mean pulmonary arterial pressure (62 (4) to 59 (4) mm Hg, NS). Adrenomedullin also decreased mean systemic arterial pressure (81 (3) to 72 (4) mm Hg, p < 0.05) and increased heart rate (73 (4) to 79 (4) beats/min, p < 0.05). Adrenomedullin decreased plasma aldosterone (9.8 (2.5) to 7.1 (1.5) ng/dl, p < 0.05) without significant changes in plasma renin activity. Plasma atrial and brain natriuretic peptides tended to decrease with adrenomedullin, although these changes did not reach significance. The haemodynamic and hormonal variables remained unchanged during placebo infusion.
Intravenous adrenomedullin has beneficial haemodynamic and hormonal effects in patients with precapillary pulmonary hypertension.
Heart (British Cardiac Society) 12/2000; 84(6):653-8. · 4.22 Impact Factor
