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J Yoshikawa

Publications and source records attributed to J Yoshikawa.

At least 163 records · Page 9Linked to original sources

Visualization of clear echocardiographic images with near field noise reduction technique: experimental study and clinical experience.

BACKGROUND: With transthoracic echocardiography, it is sometimes difficult to obtain a clear image of the apical portion of the heart because of noise near the transducer. To reduce this artifact, we have developed a new technique (near field noise reduction, NFNR) based on the digital filtering by using radiofrequency signals. This technique may be useful for the accurate measurement of the wall thickness of the myocardium in the near field. The objectives of these studies were (1) to determine the accuracy of this new technique for the measurement of wall thickness in the experimental study and (2) to determine whether the improvement in the image quality in the apical portion can be obtained in the clinical setting by using the NFNR technique. EXPERIMENTAL STUDY: By using the NFNR technique, we measured wall thickness of three kinds of phantoms (wall thickness 9.0, 14.0, and 21.0 mm) moving at various velocities (5 to 80 mm/sec) in the water bath with artifact produced by a single probe. It was difficult to obtain clear echocardiographic images of the phantom and measure its wall thickness because of the artifact. By using the NFNR technique, on the other hand, the same phantom was clearly imaged. It was possible to measure the wall thickness of each phantom at each moving velocity with the NFNR technique. Mean differences between the echocardiographic measurement and actual value of wall thickness in each phantom model (9.0, 14.0, and 21.0 mm) were 0.04 +/- 0.58 mm, 0.09 +/- 0.58 mm, and -0.02 +/- 0.24 mm, respectively. CLINICAL STUDY: We studied 25 initial patients in whom the near field was not clearly imaged in apical views by conventional echocardiography because of near field noise. Apical four-chamber or two-chamber views were obtained with and without the NFNR technique. Two observers independently graded endocardial visualization for the 50 segments by using a three-point scale (0 = endocardium not seen, 1 = seen in part but not all of the segment, 2 = endocardium seen along entire segment). The mean segment score in the imaging with the NFNR technique was significantly higher than that without the NFNR technique (observer 1: 1.8 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01; observer 2: 1.6 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01). CONCLUSIONS: The newly developed NFNR technique provides clear echocardiographic images and accurate wall thickness measurement in the experimental model even when it is difficult to obtain clear images because of the artifact. This new technique will be useful in the reduction of near field noise in the clinical setting.

Echocardiography↗

Risk factors of pneumonitis following chemoradiotherapy for lung cancer.

The purpose of this retrospective study was to identify risk factors associated with development of pneumonitis following chemoradiotherapy (CRT). We examined 60 patients (pts) who received CRT from May 1993 to August 1995. Factors evaluated included total radiation dose, field-size, irradiated site, type of chemotherapy, pulmonary fibrosis and treatment schedule (concurrent versus sequential). There were 17 pts (28.3%) who had > or = Grade 2 pulmonary toxicity. There was no significant relationship between total radiation dose, field-size > or = 200 cm2, pulmonary fibrosis or treatment schedule and risk of pneumonitis. In the sequential treatment group (22 pts), no relationship was noted between any factor and the risk of pneumonitis, while in the concurrent treatment group (38 pts), the incidence of pneumonitis was more frequent (53.8%) in patients with field-size > or = 200 cm2 than in patients with field-size < 200 cm2 (P < 0.05). In those who received concurrent treatment, including weekly CPT-11, pneumonitis was more frequent (56.3%) than in those without CPT-11 (13.6%, P < 0.01). When the lower lung field was included in the radiation site, the incidence of pneumonitis was 70% compared with 20% for other sites (P < 0.01). Multivariate analysis revealed a significant relationship between radiation site and the risk of pneumonitis (P = 0.0096). CPT-11 was significant (P = 0.038) only in the concurrent group. Pneumonitis was reversible in all but one pt by steroid therapy. Thus, irradiated site (included lower lung field) and concurrent CRT used with weekly CPT-11 were treatment factors significantly associated with a higher risk of pneumonitis following CRT.

Adult↗

Effect of cilazapril on ventricular remodeling assessed by Doppler-echocardiographic assessment and cardiac gene expression.

The purpose of this study is to determine whether the administration of the ACE inhibitor cilazapril can lessen the adverse effects of ventricular remodeling, including systolic and diastolic dysfunction, modulation of fetal gene expression, increase of collagen genes, and depression of the sarcoplasmic reticulum (SR) Ca2+ ATPase gene in a myocardial infarcted (MI) rat model. At 1 day after MI, the animals were randomly assigned to cilazapril treatment or no treatment. We performed Doppler-echocardiographic examinations and measured cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The weights of the right (RV) and left ventricles (LV) in 1- and 3-month MI rats were significantly larger than those of the control rats. Cilazapril significantly prevented the increase. The MI rats showed systolic dysfunction, as evidenced by decreased fractional shortening (control, 34 +/- 3% vs. MI, 17 +/- 3%; P < 0.01) and ejection fraction measured by the modified Simpson's method (control, 61 +/- 2% vs. MI, 36 +/- 3%; P < 0.01) in rats at 1 month after operation. MI rats showed diastolic dysfunction, defined as increased peak early filling velocity, increased deceleration rate of the early filling wave, decreased late filling velocity, and an increase in the ratio of early filling to late filling velocity. Cilazapril significantly prevented systolic and diastolic dysfunction in rats after MI. The increases in beta-MHC, alpha-skeletal actin, ANP, and collagen I and III mRNAs in the nonischemic LV and RV were significantly suppressed by treatment with cilazapril. Depressed SR Ca(2+)-ATPase mRNA (nonischemic LV, 0.7-fold, P < 0.05 vs. control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after MI was significantly restored to normal levels by cilazapril. Cilazapril improved the adverse remodeling process by attenuating the progression of systolic and diastolic dysfunction, and prevented abnormal cardiac gene expression following MI.

Angiotensin-Converting Enzyme Inhibitors↗

CYFRA 21-1, a cytokeratin subunit 19 fragment, in bronchoalveolar lavage fluid from patients with interstitial lung disease.

1. It has been suggested that CYFRA21-1, a cytokeratin subunit 19 fragment, is potentially useful for diagnosis and monitoring of lung carcinoma. However, serum levels of CYFRA21-1 are also increased in a high proportion of patients with interstitial lung disease. In this study we measured CYFRA21-1 levels in bronchoalveolar lavage fluid from 10 normal subjects, 18 patients with idiopathic pulmonary fibrosis and 14 patients with sarcoidosis, and determined whether any relationship exists between CYFRA21-1 levels in bronchoalveolar lavage fluid and clinical parameters. 2. CYFRA21-1 levels in bronchoalveolar lavage fluid were significantly higher in patients with sarcoidosis (mean value 8.3 ng/ml, P < 0.01) and idiopathic pulmonary fibrosis (42.5 ng/ml, P < 0.005) than in normal controls (1.0 ng/ml). Moreover, higher CYFRA21-1 levels in bronchoalveolar lavage fluid were found in sarcoidosis patients in radiological stage 2 or 3 than in those in stage 1. In patients with idiopathic pulmonary fibrosis, there was a significant correlation between CYFRA21-1 levels, and percentage of inflammatory cells in bronchoalveolar lavage fluid (r = 0.56, P < 0.05) and the magnitude of the alveolar--arterial oxygen pressure difference [P(A-a)O2] gradient (r = 0.66, P < 0.01). 3. Serial bronchoalveolar lavage samples were obtained from six patients with clinically active pneumonitis after they had undergone systemic corticosteroid therapy. CYFRA21-1 levels were significantly lower after these patients exhibited clinical improvement (P < 0.05). 4. These findings suggest that the level of CYFRA21-1 in bronchoalveolar lavage fluid is a useful marker for the clinical diagnosis of pneumonitis, and is also adequate for the evaluation of disease activity, especially over the course of treatment.

Adrenal Cortex Hormones↗

Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Though direct measurement of endogenous NO has been difficult in humans, we have recently found that measurement of NO derivatives in induced sputum may be useful for assessing airway inflammation in asthmatic patients. OBJECTIVE: This study was designed to determine the direct in vivo evidence of increased production of endogenous NO in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD). METHODS: We have investigated simultaneous assessment of NO using two non-invasive methods, such as NO level in exhaled air and induced sputum, in these patients. We determined the concentration of stable end-products of NO (nitrite plus nitrate) in induced sputum and exhaled NO concentration using a chemiluminescence analyser in 10 normal controls, 10 asthmatic patients and 11 patients with COPD, and evaluated whether endogenous NO levels correlate with percentage of neutrophils and interleukin-8 (IL-8) level in induced sputum in patients with COPD. RESULTS: We found significantly higher concentrations of exhaled NO in patients with bronchial asthma (25.1 [5.1] p.p.b.) than in patients with COPD (12.1 [1.9] p.p.b.) and normal controls (5.2 [1.4] p.p.b.). However, higher concentrations of NO derivatives in induced sputum were found in patients with bronchial asthma (1190 [106] micromol/L) and COPD (950 [105] micromol/L) than in normal controls (514 [30] micromol/L). In patients with asthma, but not in those with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with concentrations of exhaled NO (r = 0.64, P < 0.05). Moreover, in patients with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with percentage of neutrophils (r = 0.71, P < 0.05) and IL-8 level (r = 0.80, P < 0.01). CONCLUSION: We conclude the increased production of endogenous NO in patients with asthma and COPD, and that NO derivatives in induced sputum are more valuable than exhaled NO in assessing airway inflammation in patients with COPD.

Adult↗

Effect of the endothelin family of peptides on human coronary artery smooth-muscle cell migration.

The migration of coronary artery medial smooth-muscle cells (SMCs) is one of the key events in the process of intimal thickening in coronary atherosclerotic lesions. The objectives of the present study were to determine whether any of the three isoforms of endothelin (ET), ET-1, ET-2, and ET-3, or an intermediate form of ET, big ET-1, induces migration of human coronary artery SMCs, and to investigate the possible interaction of ET peptides and well-known migration-stimulatory factors, platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II), on SMC migration by the Boyden's chamber method. None of the ET peptides alone induced SMC migration between 10(-9) and 10(-7) mol/L. In contrast, ET-1 and ET-2 significantly induced SMC migration in the presence of low concentrations of PDGF-BB (0.5 ng/mL) or Ang II (10(-9) mol/L), although ET-3 was less active (ET-1 = ET-2 > ET-3). In contrast, big ET-1 was without significant activity on PDGF-BB-or Ang II-induced SMC migration. The potentiation of SMC migration by ET peptides was clearly inhibited by the ETA receptor antagonist BG-123 in a concentration-dependent manner. These results suggest that the ET family of peptides, especially ET-1 and ET-2, can induce human coronary artery SMC migration in combination with PDGF-BB or Ang II, probably via ETA receptors. Taken together with the finding that the concentrations of ET, PDGF-BB and Ang II are locally increased at sites of endothelial injury, this indicates that ET may be an initial stimulus for human coronary artery medial SMC recruitment during coronary atherosclerosis, possibly in combination with PDGF-BB or Ang II.

Angiotensin II↗

Heparin suppresses cyclosporine-induced endothelin-1 synthesis in rat endothelial cells.

Cyclosporine stimulates vasoconstrictor endothelin-1 (ET-1) synthesis. This study examined the effect of heparin on cyclosporine-induced ET-1 synthesis in Wistar rat aortic endothelial cells in culture. Cyclosporine (0.01-5 mumol/L) stimulated ET-1 mRNA expression in a dose-dependent manner. A nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA) (10(-5) mol/L), did not affect cyclosporine-induced ET-1 mRNA expression. Heparin (1-20 U/ml) suppressed cyclosporine-induced ET-1 mRNA expression in a dose-dependent manner. The inhibitory effect of heparin was blunted in the presence of either L-NMMA (10(-5) mol/L) or calmodulin inhibitors such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) (5 x 10(-5) mol/L) or calmidazolium (5 x 10(-5) mol/L) in the presence of the phosphodiesterase inhibitor 3-isobutyl 1-methylxanthine (0.1 mmol/L). These results suggest that heparin suppresses cyclosporine-induced ET-1 mRNA expression via both NO- and calmodulin-dependent pathways.

Animals↗

Suppression of endothelin-3-induced nitric oxide synthesis by triglyceride in human endothelial cells.

Reduced endothelium-derived nitric oxide (NO) production characterizes several vascular diseases. This study examined the effect of triglyceride on NO production induced by endothelin-3 (ET-3) in cultured human umbilical vein endothelial cells. Triglyceride-rich human plasma obtained after a high-carbohydrate diet with white wine was used in an ex vivo study. The plasma triglyceride fraction was found to consist of large amounts of palmitic and oleic acids detected by gas-liquid chromatography. Therefore, the effect of synthetic tripalmitin and triolein emulsion on NO production was also examined. ET-3 stimulated NO and guanosine 3',5'-cyclic monophosphate production and increased cytosolic Ca2+ levels in the endothelial cells (ECs). After incubation of the ECs with the triglyceride-rich plasma for 2 h, these responses to ET-3 were ameliorated in a triglyceride concentration-dependent manner (50-200 mg/dl). A synthesized emulsion of tripalmitin (100 mg/dl) and triolein (100 mg/dl) also blunted the responses to ET-3. Neither endothelial constitutive NO synthase mRNA expression nor its protein level was affected by treatment with triglycerides. These results suggest that triglyceride suppresses ET-3-induced NO synthesis in human ECs by inhibiting cytosolic Ca2+ elevation.

Blotting, Northern↗

Hypervascular hepatocellular carcinoma: evaluation of hemodynamics with dynamic CT during hepatic arteriography.

PURPOSE: To assess the hemodynamics and the main drainage vessel of hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: Single-level dynamic computed tomography during hepatic arteriography (CTHA) was performed in 32 patients with hepatocellular carcinoma. Carcinoma was confirmed with histologic (n = 9) or clinical (n = 23) examination results. Single-level CTHA findings were retrospectively analyzed. Histologic specimens from 40 livers with hepatocellular carcinoma were also examined, with special attention to vessels along the rim of the lesion. RESULTS: Contrast material enhancement on single-level CTHA images occurred in four phases: (a) inflow of the contrast material into tumor, (b) tumor enhancement, (c) inflow of the contrast material into adjacent liver, and (d) corona enhancement of adjacent liver. Corona enhancement was seen in all lesions. A bright branching structure in the corona enhancement area, suggestive of a portal venule, was visible at the start of adjacent liver staining in 21 lesions. Continuity between a tumor sinusoid and a tiny vessel in the inner layer of the pseudocapsule was histologically confirmed in 10 of 40 specimens. Continuity between a tiny vessel in the inner layer and a portal vein in the outer layer of the pseudocapsule was confirmed with findings on serial sections from one liver. CONCLUSION: The main drainage of hepatocellular carcinoma lesions may be a protal venule.

Carcinoma, Hepatocellular↗

Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma.

Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.

Adolescent↗

Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs.

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.

Aerosols↗

A case of dobutamine-induced coronary arterial spasm with ST-segment elevation.

A 55-year-old Japanese woman demonstrated ST-segment elevation in leads I, aVL, and V3-V6 with chest pain both in an ergometer exercise test and on dobutamine stress echocardiography. Although the baseline coronary arteriogram revealed no organic stenosis, total occlusion of the distal portion of the posterolateral branch of the left circumflex artery was observed during dobutamine infusion with ST-segment elevation and chest pain. This is a rare case of documented dobutamine-induced coronary arterial spasm.

Coronary Vasospasm↗

Doppler echocardiographic assessment and cardiac gene expression analysis of the left ventricle in myocardial infarcted rats.

The purpose of this study was to examine cardiac geometry and function by Doppler echocardiography and to analyze mRNA expression of cardiac phenotype and extracellular matrix in myocardial infarcted rats. Doppler echocardiograms and hemodynamics were measured 2 weeks after myocardial infarction (MI). mRNA levels in the non-infarcted left ventricle (LV) and infarct site were measured by Northern blot analysis. LV internal diastolic dimension was greater in infarcted (MI) than in sham-operated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+0.3 mm, p<0.01). The fractional shortening decreased in MI rats (MI 32+4% vs control 61+/-3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling wave was more rapid in rats with MI (MI 25.1+/-2.8 m/sec2 vs control 12.4+/-1.7 m/sec2, p < 0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control 35+/-6 cm/sec, p <0.05), resulting in a marked increase in the ratio of early filling to late filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels for beta-myosin heavy chain (beta-MHC), a-skeletal actin, atrial natriuretic polypeptide (ANP), collagen types I and III, and matrix metalloproteinase 2 (MMP-2) in the non-infarcted LV increased significantly by 1.8-, 2.4-, 4.7-, 2.6-, 2.1- (all p<0.01) and 1.4-fold (p<0.05), respectively, compared with sham-operated myocardium. In the infarct site, mRNA levels for transforming growth factor (TGF)-beta1, collagen types I and III, and MMP-2 significantly increased by 3.2-, 11.0-, 9.7-, and 6.3-fold (all p<0.01), respectively, compared with sham-operated myocardium. Myocardial infarcted rat was characterized by cavity dilation and marked abnormalities of systolic and diastolic function, accompanied by a shift of myocytes to fetal phenotype and activation of collagen genes in the non-infarcted myocardium.

Actins↗

Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophy.

We examined the effect of a calcium antagonist, manidipine hydrochloride, on cardiac hypertrophy and the expression of the atrial natriuretic peptide (ANP), transforming growth factor beta 1 (TGF-beta 1), and extracellular matrix protein genes in rats with isoproterenol-induced cardiac hypertrophy. Rats were continuously infused with saline or isoproterenol (0.5 mg/kg per day) for 7 days using an osmotic minipump. Treatment with manidipine hydrochloride (once a day at 3 mg/kg) began 1 day before minipump implantation and continued until the end of the experiments (each group; n = 6). After treatment, left ventricular weight was measured and mRNA was extracted and analyzed by Northern blot hybridization. Isoproterenol increased left ventricular weight (2.40 +/- 0.04 g/kg; p < 0.01) without increasing blood pressure. ANP, collagen type I and type III, and fibronectin mRNAs were increased 1.5-(p < 0.01), 1.9- (p < 0.01), 2.7- (p < 0.01), and 3.2-fold (p < 0.01), respectively, by isoproterenol infusion. However, TGF-beta 1, collagen type IV, and laminin B1 and B2 mRNA levels were unchanged by isoproterenol. Manidipine hydrochloride prevented isoproterenol-induced left ventricular hypertrophy (2.26 +/- 0.02 g/kg; p < 0.01) and expression of mRNA of ANP (0.9-fold of the control value; p < 0.01), collagen types I (1.1-fold; p < 0.01) and type III (1.6-fold; p < 0.01), and fibronectin (1.1-fold; p < 0.01). Thus, manidipine hydrochloride prevented cardiac hypertrophy and changes in the expression of genes for ANP and interstitial components of extracellular matrix induced by isoproterenol.

Animals↗

The effect of vasopressin V1- and V2-receptor antagonists on hemodynamics in early and late phase after myocardial infarction in rats.

This study was designed to assess the effect of a nonpeptide vasopressin V1-receptor antagonist, OPC-21268, and a vasopressin V2-receptor antagonist, OPC-31260, on hemodynamics in the early phase and the late phase after myocardial infarction in rats. In the early phase, OPC-21268 (30 mg/kg/day) or OPC-31260 (30 mg/kg/day) was orally administered from day 1 to day 5 after the operation; and hemodynamics were measured at day 5, in the late phase from 10 weeks to 11 weeks and measured at the end of 11 weeks. In the early phase, OPC-21268 reduced the left ventricular end-diastolic pressure (LVEDP) concomitantly with the reduction in systemic blood pressure, but did not change LVEDP in the late phase. OPC-31260 reduced LVEDP and central venous pressure in both phases. OPC-21268 improved hemodynamics only in the early phase and OPC-31260 improved it in both phases.

Administration, Oral↗

Angiotensin II type 1-receptor antagonist candesartan cilexitil prevents left ventricular dysfunction in myocardial infarcted rats.

The purpose of this study was to analyze the effect of the angiotensin II type 1-receptor antagonist candesartan cilexitil on left ventricular systolic and diastolic function and mRNA expression of contractile proteins, collagen, and Ca2+ handling protein in myocardial-infarcted rats. After myocardial infarction, the animals were randomly assigned to candesartan cilexitil-treated or untreated groups (MI). We performed Doppler-echocardiographic examination and measured the hemodynamics at four and twelve weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. At four weeks in MI, left ventricular end-diastolic dimension increased (Control, 6.2+/-0.6 mm; MI, 8.7+/-0.6 mm; P < 0.01), fractional shortening decreased (Control, 41+/-5%; MI, 16+/-3%; P < 0.01) and E wave deceleration rate increased (Control, 14.3+/-2.0 m/sec2; MI, 23.3+/-2.3 m/sec2; P < 0.01). Candesartan cilexitil significantly prevented these changes. The mRNA expressions of beta-myosin heavy chain, alpha-skeletal actin, atrial natriuretic peptide, and collagens I and III in the non-infarcted left ventricle and right ventricle were increased at four weeks and were significantly suppressed by treatment with candesartan cilexitil. At four weeks, Na+-Ca2+ exchanger mRNA expression was increased, and candesartan cilexitil suppressed this increase. At twelve weeks, sarcoplasmic reticulum Ca2+-ATPase mRNA expression in the infarcted region including the adjacent non-infarcted left ventricle and right ventricle were decreased and candesartan cilexitil restored it to the control level. Candesartan cilexitil prevented the systolic and diastolic dysfunction and abnormal cardiac mRNA expression in myocardial-infarcted rats.

Angiotensin Receptor Antagonists↗

Assessment of cardiac function and gene expression at an early phase after myocardial infarction.

The purpose of this study was to examine left ventricular function and cardiac gene expressions at an acute phase after myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Two days after MI, we performed Doppler-echocardiography and measured the systolic and diastolic function. We then analyzed the contractile protein and extracellular matrix mRNAs of cardiac tissues in the infarcted region, including the adjacent noninfarcted myocardium (the adjacent noninfarcted myocardium) and the remote noninfarcted myocardium, by Northern blot hybridization. Fractional shortening decreased significantly to 28%. Peak early diastolic filling wave (E wave) velocity increased in MI rats (MI; 90 +/- 3 cm/s versus the control; 71 +/- 2 cm/s, p < 0.05), and the deceleration rate of the E wave velocity was more rapid in MI rats (MI; 22.0 +/- 2.6 m/s2 versus the control; 16.5 +/- 2.0 m/s2, p < 0.01). Atrial filling wave (A wave) velocity decreased, resulting in a marked increase in the ratio of E wave to A wave velocity (MI; 3.1 +/- 0.3 versus the control; 2.1 +/- 0.2, p < 0.01). In the adjacent noninfarcted myocardium, mRNA levels for alpha-skeletal actin, atrial natriuretic polypeptide (ANP), transforming growth factor-beta 1(TGF-beta 1), fibronectin, and collagen types I and III increased significantly. In the remote noninfarcted myocardium, mRNA levels for alpha-skeletal actin, ANP, and collagen types I and III increased, while mRNA levels for beta-myosin heavy chain, TGF-beta 1 and fibronectin did not change. We observed left ventricular dysfunction and different gene expression between adjacent noninfarcted myocardium and in the remote noninfarcted myocardium two days after MI. These findings suggest that cardiac gene expression after MI may be a compensation reaction for cardiac dysfunction induced by myocardial damage.

Animals↗

Clinical implication of protein levels of IL-5 in induced sputum in asthmatic patients.

To determine whether protein levels of interleukin-5 (IL-5) in induced sputum reflect the degree of eosinophilic inflammation, we evaluated the role of IL-5 on clinical characteristics in stable asthmatic patients. IL-5 level, differential eosinophil count, and level of eosinophil cationic protein (ECP) in induced sputum were all significantly higher for asthmatics than for normal controls. Both eosinophil counts and ECP levels in induced sputum were inversely correlated with the degree of airflow limitation (FEV1/FVC). In addition, patients with measurable IL-5 in sputum had significantly more eosinophils, higher levels of ECP in sputum, and lower FEV1 (percent predicted) than did patients with levels of IL-5 beneath the limit of detection. However, we found no significant difference in IL-5 levels between atopic and nonatopic asthmatics. IL-5 level in induced sputum is a good indicator of eosinophilic inflammation in atopic and nonatopic asthmatic patients.

Adult↗