Biomedical subjects

Mitsunori Iwase

Publications and source records attributed to Mitsunori Iwase.

At least 19 recordsLinked to original sources

PubMed2006

Attenuation of oxidative stress and cardiac dysfunction by bisoprolol in an animal model of dilated cardiomyopathy.

Oxidative stress is an important susceptibility factor for dilated cardiomyopathy. We have investigated the effects of bisoprolol, a beta1-selective adrenoceptor blocker, on oxidative stress and the development of cardiac dysfunction in a model of dilated cardiomyopathy. Male TO-2 and control hamsters at 8 weeks of age were treated with bisoprolol (5 mg/kg per day) or vehicle for 4 weeks. Treatment with bisoprolol prevented the progression of cardiac dysfunction in TO-2 hamsters. This drug did not affect the increase in NADPH oxidase activity but prevented the reduction in activity and expression of mitochondrial manganese-dependent superoxide dismutase as well as the increases in the concentrations of interleukin-1beta and tumor necrosis factor-alpha in the left ventricle of TO-2 hamsters. Attenuation of the development of cardiac dysfunction by bisoprolol may thus result in part from normalization of the associated increases in the levels of oxidative stress and pro-inflammatory cytokines in the left ventricle.

Aldehydes↗

PubMed2006

Sex differences in the relationships between electrocardiographic abnormalities and the extent of left ventricular hypertrophy by echocardiography.

BACKGROUND: Several criteria have been proposed for the electrocardiographic diagnosis of left ventricular hypertrophy (LVH). However, their diagnostic accuracy is questionable. Furthermore, the diagnostic accuracy of abnormalities in ST-T patterns for LVH is known to be uncertain, especially in women. We examined the relationship between electrocardiographic abnormalities and the extent of LVH. METHODS: We studied 76 men and 48 women who satisfied electrocardiographic voltage criteria for LVH (RV(5) or RV(6)> or = 2.6 mV, SV(1) + RV(5) or SV(1) + RV(6)> or = 3.5 mV). They were classified into three groups based on ST-T pattern: normal, early strain, and strain. We defined echocardiographic evidence of LVH as an LV wall thickness > or = 12 mm. RESULTS: LVH was identified by echocardiography in 55.3% of men and in 47.9% of women. In strain and early strain groups, the prevalence of echocardiographic LVH was significantly higher in men than in women (strain group: 100 vs 75%, P < 0.05, early strain group: 81.8 vs 42.1%, P < 0.05), it did not differ significantly between men and women in normal group. In men, QRS voltage values were significantly correlated with echocardiographic indices. In group strain of men, significant good correlations were observed between QRS voltage values and echocardiographic indices. However, in women, there were no significant correlation between QRS voltage values and echocardiographic indices even in strain group. CONCLUSIONS: The combined criteria of both QRS voltage and ST-T classification could provide a greater accuracy in diagnosing LVH compared to the criteria using QRS voltage alone in men rather than in women.

Echocardiography↗

PubMed2006

Differential myolysis of myocardium and skeletal muscle in hamsters with dilated cardiomyopathy: beneficial protective effect of diltiazem.

BACKGROUND: Although dilated cardiomyopathic hamsters (TO-2) with mutation of the delta-sarcoglycan gene exhibit histological features of muscular dystrophy, it remains to be elucidated whether both myocardium and skeletal muscle are injured in a similar manner. METHODS AND RESULTS: The progression of myolysis in both myocardium and skeletal muscle were assessed biochemically and pathologically in TO-2 and F1B control hamsters. Left ventricular (LV) function was assessed by echocardiography and cardiac catheterization. Both the plasma concentration of cardiac troponin T and the plasma activity of alpha-hydroxybutyrate dehydrogenase (HBD) peaked at 8 weeks of age, and thereafter reduced greatly in TO-2 hamsters. Activity of creatine kinase (CK) in TO-2 hamsters was significantly greater than in controls throughout the observation period. Pathological findings of both nuclear chain and central nuclei in skeletal muscles were observed in TO-2 hamsters throughout the observation period, suggesting regeneration. LV dysfunction was first evident at 8 weeks of age and deteriorated thereafter in TO-2 hamsters. Treatment of TO-2 hamsters with diltiazem from 5 to 8 weeks of age could avert the LV functional deterioration and the increment in alpha-HBD activity, but CK activity was unchanged. CONCLUSIONS: Despite myolysis in skeletal muscle occurring consistently throughout the observation period, cardiac myolysis occurred predominantly in the early phase. These initial cardiac events might involve coronary spasm and/or calcium overload in the myocardium.

Animals↗

PubMed2006

The distal protection during primary percutaneous coronary intervention alleviates the adverse effects of large thrombus burden on myocardial reperfusion.

BACKGROUND: The presence of intracoronary large thrombus burden (LTB) in the infarct-related artery increases the risk of distal embolization and no-reflow during percutaneous coronary intervention (PCI). Evaluation of whether the distal protection (DP) during primary PCI reduces adverse effects of LTB on myocardial reperfusion and infarct size was investigated. METHODS AND RESULTS: A consecutive series of 88 patients with acute myocardial infarction undergoing primary PCI using DP were compared with 81 consecutive patients treated by primary PCI alone. The DP use showed similar post-procedural myocardial blush grade (MBG)-3 and infarct size, but improved corrected thrombolysis in myocardial infarction frame count (cTFC) (29+/-11 vs 35+/-20, p=0.011) and the incidence of ST-segment resolution (80.7% vs 66.7%, p=0.038). In patients with LTB present, however, the DP use reduced occurrences of no-reflow (0% vs 11.8%, p=0.036) and distal embolization (4.8% vs 17.6%, p=0.129), resulting in higher occurrences of MBG-3 (61.9% vs 35.3%, p=0.021) and ST-segment resolution (78.6% vs 50.0%, p=0.009), lower cTFC values (30+/-8 vs 40+/-22, p=0.012) and smaller infarct size (12.2+/-11.2 vs 18.7+/-11.1, p=0.015). CONCLUSIONS: With an improved myocardial reperfusion and smaller infarct size in patients with LTB, the DP during primary PCI might be a better strategy in this particular setting compared with conventional strategy.

Acute Disease↗

PubMed2005

Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway.

The possible role of calcineurin in cardiac hypertrophy induced by calmodulin (CaM) overexpression in the heart was investigated. CaM transgenic (CaM-TG) mice developed marked cardiac hypertrophy and exhibited up-regulation of atrial natriuretic factor (ANF) and beta-myosin heavy chain gene expression in the heart during the first 2 weeks after birth. The activity of calcineurin in the heart was also significantly increased in CaM-TG mice compared with wild-type littermates. Treatment of CaM-TG mice with the calcineurin inhibitor FK506 (1mg/kg per day) prevented the increase in the heart-to-body weight ratio as well as that in cardiomyocyte width. FK506 also inhibited the induction of fetal-type cardiac gene expression in CaM-TG mice. Overexpression of CaM in cultured rat cardiomyocytes activated the ANF gene promoter in a manner sensitive to FK506. Activation of a calcineurin-dependent pathway thus contributes to the development of cardiac hypertrophy induced by CaM overexpression in the heart.

Animals↗

PubMed2005

Nicorandil promotes myocardial capillary and arteriolar growth in the failing heart of Dahl salt-sensitive hypertensive rats.

Long-term administration of vasodilators increases shear stress, which is thought to be important for vascular growth in the heart. Nicorandil, an activator of ATP-sensitive potassium channels with a nitrate-like action, is a potent vasodilator. We have now investigated the effects of nicorandil on vascular growth and gene expression in the failing heart of Dahl salt-sensitive (DS) hypertensive rats. DS rats fed a high-salt diet from 6 weeks of age develop concentric cardiac hypertrophy secondary to hypertension at 11 weeks, followed by heart failure at 18 weeks. DS rats on such a diet were treated with a nonantihypertensive oral dose of nicorandil (6 mg/kg per day) or vehicle from 11 to 18 weeks of age. Treatment of DS rats with nicorandil improved cardiac function and attenuated the development of heart failure. Myocardial capillary and arteriolar densities did not differ between vehicle-treated DS rats and age-matched controls. The abundance of mRNAs for endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF), the VEGF receptor Flt-1, and basic fibroblast growth factor (bFGF) in the myocardium was markedly reduced in vehicle-treated DS rats compared with controls. Treatment of DS rats with nicorandil greatly increased capillary and arteriolar densities and inhibited the downregulation of eNOS, VEGF, fms-like tyrosin kinase-1, and bFGF gene expression. This, nicorandil stimulates coronary capillary and arteriolar growth and thereby likely suppresses the development of heart failure in DS rats. Nicorandil may prove beneficial for the treatment of hypertensive heart failure as well as of ischemic heart disease.

Animals↗

PubMed2005

Endotoxin from various gram-negative bacteria has differential effects on function of hepatic cytochrome P450 and drug transporters.

The differential effects of endotoxin derived from Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli on hepatic cytochrome P450 (CYP)-dependent drug-metabolizing enzyme activity and on the expression of hepatic CYP3A2, CYP2C11, P-glycoprotein and multidrug resistance-associated protein 2 (Mrp2) was investigated in rats. Endotoxin from all three different pathogens significantly decreased the systemic clearance of antipyrine, reflecting reduced hepatic drug-metabolizing enzyme activity 24 h after intravenous injection (0.5 mg/kg). The degree of the decreased systemic clearance by P. aeruginosa endotoxin was smaller than that by both K. pneumoniae and E. coli endotoxin. Western blot analysis revealed that the down-regulation of CYP3A2 by K. pneumoniae and E. coli endotoxin was greater than that by P. aeruginosa endotoxin. However, the down-regulation of CYP2C11 by all three different endotoxin was almost the same. Both K. pneumoniae and P. aeruginosa endotoxin significantly down-regulated P-glycoprotein, but did not down-regulate Mrp2. E. coli endotoxin had no effect on the expression of either P-glycoprotein or Mrp2, probably due to the low dose used. The down-regulation of CYP3A2 by endotoxin was parallel to the decreased systemic clearance of antipyrine. These results suggest that endotoxin has a differential effect on the hepatic CYP-mediated drug-metabolizing enzyme activity, and on the protein levels of hepatic CYP3A2 and P-glycoprotein, probably due to bacterial source-differences in the production of some proinflammatory mediators. Endotoxin appears to regulate coordinately CYP3A2, CYP2C11 and P-glycoprotein, but not Mrp2.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Cardiac 123I-MIBG reflects left ventricular functional reserve in patients with nonobstructive hypertrophic cardiomyopathy.

UNLABELLED: Little is known about the relation between left ventricular (LV) functional reserve in response to exercise and cardiac sympathetic nervous function in patients with nonobstructive hypertrophic cardiomyopathy (HCM). We investigated whether an assessment of cardiac sympathetic nervous function by myocardial (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy might provide a sign of an abnormal LV functional reserve in response to exercise-induced beta-adrenergic stimulation in patients with HCM. METHODS: Thirty HCM patients underwent (123)I-MIBG scintigraphy and echocardiography at rest and subsequent biventricular cardiac catheterization at rest and during dynamic exercise. LV pressures were measured using a micromanometer-tipped catheter system. The early and delayed (123)I-MIBG images were quantified as a heart-to-mediastinum ratio (H/M). The plasma levels of brain natriuretic peptide (BNP) and norepinephrine (NE) were also measured. RESULTS: Patients were divided into 2 groups according to the delayed (123)I-MIBG H/M: group I consisted of 12 patients with a delayed H/M of < or =1.8 and group II had 18 patients with a delayed H/M of >1.8. Both the percentage increase from rest to exercise in LV isovolumic contraction (LV dP/dt(max)) and the percentage shortening of LV pressure half-time (T(1/2)) as an index of isovolumic relaxation were significantly less in group I than in group II (P < 0.05, respectively). A significant linear correlation was observed between the percentage increase in LV dP/dt(max) and (123)I-MIBG H/Ms (early H/M: r = 0.49, P < 0.01; delayed H/M: r = 0.54, P < 0.005, respectively). A significant linear correlation was also observed between the percentage shortening in T(1/2) and (123)I-MIBG H/Ms (early H/M: r = 0.58, P < 0.001; delayed H/M: r = 0.64, P < 0.0005, respectively). The plasma NE levels were significantly higher in group I than in group II (P < 0.01), whereas the plasma BNP levels were comparable in the 2 HCM groups. CONCLUSION: beta-Adrenergic enhancement of LV function during exercise may depend on the extent of cardiac sympathetic nervous innervation in HCM patients. Resting myocardial (123)I-MIBG scintigraphy can noninvasively evaluate LV functional reserve in response to exercise in patients with nonobstructive HCM.

3-Iodobenzylguanidine↗

PubMed2004

Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography.

BACKGROUND: The differentiation of hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological information obtained by conventional echocardiography is occasionally problematic. We investigated whether strain rate (SR) imaging derived from tissue Doppler imaging (TDI) is able to discriminate HCM from H-LVH. METHODS AND RESULTS: Conventional echocardiography and TDI were performed with 34 patients with LVH and 16 reference subjects. Mean values of systolic strain (epsilon(sys)), peak systolic SR, and early diastolic SR obtained from 8 left ventricular (LV) segments were calculated. LV pressures were recorded simultaneously in the patients. Patients were diagnosed with HCM (n=20) or H-LVH (n=14) on the basis of conventional echocardiography and endomyocardial biopsy findings. Multivariate analysis revealed that septum/posterior wall thickness ratio (P=0.00013) and epsilon(sys) (P<0.0001) were each able to discriminate HCM from H-LVH. A epsilon(sys) cutoff value of -10.6% discriminated between HCM and H-LVH with a sensitivity of 85.0%, specificity of 100.0%, and predictive accuracy of 91.2%. The combination of the septum/posterior wall thickness ratio and epsilon(sys) discriminated HCM from H-LVH with a predictive accuracy of 96.1%. The epsilon(sys) parameter was significantly correlated with pulmonary arterial wedge pressure, LV end-diastolic pressure, the peak positive first derivative of LV pressure, and the time constant of LV pressure decay. CONCLUSIONS: SR imaging is able to discriminate HCM from H-LVH, with epsilon(sys) reflecting myocardial contractile and lusitropic properties.

Aged↗

PubMed2004

Effect of pioglitazone on endotoxin-induced decreases in hepatic drug-metabolizing enzyme activity and expression of CYP3A2 and CYP2C11.

It has been reported that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands ameliorate the expression of inducible nitric oxide synthase (iNOS) by endotoxin. In the present study, we investigated the effect of pioglitazone, a potent PPAR-gamma ligand, on the endotoxin-induced reduction of hepatic drug-metabolizing enzyme activity and on the down-regulation of the expression of hepatic cytochrome P450 (CYP) 3A2 and CYP2C11 proteins in rats. Endotoxin (1 mg/kg) significantly decreased hepatic drug-metabolizing enzyme activity in vivo, as represented by the systemic clearance of antipyrine and protein levels of CYP3A2 and CYP2C11 24 h after intraperitoneal injection. Pretreatment with pioglitazone (10 mg/kg, 4 times at 10-min intervals) significantly protected the endotoxin-induced decreases in the systemic clearance of antipyrine and protein levels of CYP3A2, but not CYP2C11, with no biochemical and histopathological changes in the liver. Pioglitazone alone had no effect on the systemic clearance of antipyrine and protein levels of CYP3A2 or CYP2C11. Pioglitazone significantly protected endotoxin-induced overexpression of iNOS in the liver, but not the overproduction of nitric oxide (NO) in plasma. It is unlikely that the protective effect of pioglitazone against endotoxin-induced decreases in the hepatic drug-metabolizing enzyme activity and protein levels of CYP3A2 in the liver is due to the inhibition of the overproduction of NO.

Animals↗

PubMed2004

Glucose intolerance, as reflected by hemoglobin A1c level, is associated with the incidence and severity of transplant coronary artery disease.

OBJECTIVES: The possible effect of plasma hemoglobin A(1c) (HbA(1c)) on the development of transplant coronary artery disease (TxCAD) was investigated. BACKGROUND: Glucose intolerance is implicated as a risk factor for TxCAD. However, a relationship between HbA(1c) and TxCAD has not been demonstrated. METHODS: Plasma HbA(1c) was measured in 151 adult patients undergoing routine annual coronary angiography at a mean period of 4.1 years after heart transplantation. Intracoronary ultrasound (ICUS) was also performed in 42 patients. Transplant CAD was graded by angiography as none, mild (stenosis in any vessel < or =30%), moderate (31% to 69%), or severe (> or =70%) and was defined by ICUS as a mean intimal thickness (MIT) > or =0.3 mm in any coronary artery segment. The association between TxCAD and established risk factors was examined. RESULTS: Plasma HbA(1c) increased with the angiographic grade of TxCAD (5.6%, 5.8%, 6.4%, and 6.2% for none, mild, moderate, and severe disease, respectively; p < 0.05 for none vs. moderate or severe) and correlated with disease severity (r = 0.24, p < 0.05). The HbA(1c) level was higher in patients with MIT > or =0.3 mm than in those with MIT <0.3 mm (6.4% vs. 5.7%, p < 0.05). Multivariate logistic regression analysis identified HbA(1c) as an independent predictor of TxCAD, as detected by angiography or ICUS (odds ratios 1.9 and 2.4, 95% confidence intervals 1.5 to 6.3 [p = 0.010] and 1.3 to 4.2 [p < 0.005], respectively). CONCLUSIONS: Persistent glucose intolerance, as reflected by plasma HbA(1c), is associated with the occurrence of TxCAD and may play an important role in its pathogenesis.

Adolescent↗

PubMed2004

Growth hormone-releasing peptide can improve left ventricular dysfunction and attenuate dilation in dilated cardiomyopathic hamsters.

OBJECTIVE: The mammalian heart contains specific growth hormone-releasing peptide (GHRP) binding sites whose physiological significance is unknown. We sought to compare the effects of GHRP and GH on progressive left ventricular (LV) dysfunction in the TO-2 hamster model of dilated cardiomyopathy. METHODS: TO-2 hamsters (8 weeks old) were injected with GHRP-6 (100 microg/kg day), GH (2 mg/kg day), or saline for 4 weeks; F1B hamsters served as controls. LV functional and structural changes were evaluated by echocardiography and pathology. RESULTS: The increase in body weight of GH-treated TO-2 hamsters was greater than that of animals in the other two groups. Plasma GH and insulin-like growth factor-1 (IGF-1) concentrations were not increased by GHRP-6. LV fractional shortening (LVFS) decreased from 42.0+/-2.6% to 25.4+/-1.8% and the LV end-diastolic dimension (LVDd) increased from 4.0+/-0.1 to 5.0+/-0.1 mm in untreated TO-2 hamsters between 8 and 12 weeks. LVFS was substantially improved by treatment with GHRP-6 (33.4+/-2.0%) or GH (32.0+/-2.1%). The LVDd was significantly smaller in animals treated with GHRP-6 than in those treated with GH. The cross-sectional LV myocyte area and the amount of atrial natriuretic peptide mRNA in the LV were increased by GH but not by GHRP-6. Treatment woth GH at a lower dose (0.2 mg/(kg day)) exerted minimal cardiac and systematic growth effects without improving LV function. CONCLUSION: GHRP can ameliorate the development of progressive LV dysfunction independently of the GH-IGF-1 axis, suggesting a potential new approach to the heart failure.

Animals↗

PubMed2004

Promising efficacy of primary gradual and prolonged balloon angioplasty in small coronary arteries: a randomized comparison with cutting balloon angioplasty and conventional balloon angioplasty.

BACKGROUND: Small vessel size represents a critical risk factor for an adverse outcome after both conventional balloon angioplasty (POBA) and stenting. Gradual and prolonged balloon angioplasty (GPBA) has been shown to cause less arterial trauma, which results in higher procedural success rates and fewer in-hospital complications than POBA. The aim of this study was to assess the clinical and angiographic benefits of primary GPBA with a perfusion balloon in small coronary arteries, as compared with cutting balloon angioplasty (CBA) and POBA. METHODS: A total of 263 patients with symptoms and reference diameters <3.0 mm were randomly assigned to undergo GPBA (n = 85), CBA (n = 88), or POBA (n = 90). The cumulative inflation time must be >10 minutes in GPBA. Crossover to stent was allowed for inadequate results. Follow-up angiography was performed after 6 months. The primary end point was angiographic restenosis at follow-up. RESULTS: Compared with POBA, GPBA resulted in a lower final residual diameter stenosis (27.3% vs 34.2%, P =.01) and decreased the need for stent placement (8.0% vs 22.2%, P =.031). At follow-up, the restenosis rates were lower with GPBA (31.3%, P =.034) and CBA (32.9%, P =.059) than POBA (50.6%). Target lesion revascularization was less frequently needed with GPBA (20.5%, P =.043) and CBA (20.0%, P =.033) than POBA (37.6%). Additionally, the event-free survival rate was higher with GPBA (77.1%, P =.033) and CBA (76.4%, P =.047) than POBA (58.8%). CONCLUSIONS: In small coronary arteries, both GPBA and CBA resulted in favorable angiographic and clinical outcomes. With a lower restenosis rate and target lesion revascularization rate, GPBA may be a superior strategy for small vessels compared with POBA.

Aged↗

PubMed2004

A sensitive colorimetric assay for polyamines in erythrocytes using oat seedling polyamine oxidase.

BACKGROUND: Most of the polyamines circulating in blood are spermidine (Spd) and spermine (Spm) with only trace amounts of putrescine (Put), and they are mainly localized in erythrocytes. We developed a simple and sensitive colorimetric assay for polyamines in erythrocytes using oat seedling polyamine oxidase (OSPO). The method is based on the unique substrate specificity of OSPO, which is active toward Spd and Spm, but not toward diamines such as Put and cadaverine and monoamines such as histamine. METHODS: The polyamines, which were purified from packed erythrocytes by weak cation-exchange chromatography, were incubated with OSPO at 37 degrees C for 15 min. In the presence of the H(2)O(2) produced by this polyamine oxidase reaction and a new chromogen, N-(carboxymethylaminocarbonyl)-4,4'-bis(dimethylamino)-diphenylamine sodium salt (DA-64), peroxidase (POD) catalyzes the formation of N-[4-[[4-(dimethylamino)phenyl]imino]-2,5-cyclohexadien-1-ylidene]-N-methylmethanaminium chloride (Bindschedler's Green) having an absorption maximum at 727 nm. RESULTS: The detection limit was 0.2 microM/l for packed erythrocytes. The within-run and between-run precisions (coefficient of variation, CVs) were 5.6-15.2% and 6.5-16.4%, respectively. Analytical recoveries were 93.3-97.4%. Polyamine values obtained by this assay correlated well with those obtained by an HPLC (y=0.948x + 1.912; r=0.944; n=46). CONCLUSIONS: This colorimetric assay is simple and highly sensitive and practical for clinical use.

Adult↗

PubMed2004

Increased expression of plasminogen activator inhibitor-1 in cardiomyocytes contributes to cardiac fibrosis after myocardial infarction.

Plasminogen activator inhibitor-1 (PAI-1) plays a critical role in tissue fibrosis by inactivating matrix metalloproteinases, which might effect on the progression of left ventricular dysfunction. However, little has been known about the expression of PAI-1 during cardiac remodeling. We used a mouse model of myocardial infarction (MI) by coronary ligation, in which the progression of left ventricular remodeling was confirmed by echocardiography. Histological examination showed that interstitial and perivascular fibrosis progressed in the post-MI (PMI) heart at 4 weeks after the procedure. We observed the dramatic induction of cardiac PAI-1 mRNA and PAI-1 antigen in plasma in the PMI mice, as compared with the sham-operated (sham) mice. In situ hybridization analysis demonstrated that strong signals for PAI-1 mRNA were localized to cardiomyocytes in the border of infarct area and around fibrous lesions, and to perivascular mononuclear cells, which seemed to be mast cells, only in hearts of the PMI mice. Importantly, less development of cardiac fibrosis after MI was observed in mice deficient in PAI-1 as compared to wild-type mice. The mRNA expression of cytokines, transforming growth factor-beta, and tumor necrosis factor-alpha, was also increased in hearts of the PMI mice, but not in the sham mice. These observations suggest that cardiomyocytes and mast cells contribute to the increased PAI-1 expression, resulting in the development of interstitial and perivascular fibrosis in the PMI heart, and that the regional induction of cytokines may be involved in this process.

Animals↗

PubMed2004

Serial alterations of beta-adrenergic signaling in dilated cardiomyopathic hamsters: possible role of myocardial oxidative stress.

BACKGROUND: The relationship between enhanced myocardial oxidative stress and impaired beta-adrenergic signaling remains to be characterized during the development of dilated cardiomyopathy. METHODS AND RESULTS: Alterations in myocardial oxidative stress and beta-adrenergic signaling, as well as left ventricular (LV) functional and structural changes, were evaluated during the development of cardiomyopathy in TO-2 hamsters; F1B hamsters served as controls. LV dysfunction was first apparent at 8 weeks of age and deteriorated thereafter in the TO-2 hamsters. At 32 weeks, the animals exhibited heart failure with an increased plasma norepinephrine concentration. Cardiac myolysis, as demonstrated by elevated plasma concentration of cardiac troponin T, peaked at 8 weeks. The glutathione redox ratio revealed increased oxidative stress in the LV myocardium in TO-2 hamsters even at 4 weeks and became manifest after 8 weeks. The hearts of TO-2 hamsters had significantly reduced superoxide dismutase activity from 8 weeks onward compared with control hamsters. However, glutathione peroxidase activity was unchanged at any time point. The LV functional response to isoproterenol was markedly reduced at 8 weeks, without any apparent changes in the amount of beta-adrenergic signaling molecules, and it deteriorated thereafter. Adenylyl cyclase activity was significantly decreased, despite increased amounts of both G(s) alpha mRNA and protein, in the LV myocardium at 18 weeks. CONCLUSIONS: Myocardial oxidative stress is actually enhanced in the initial development of LV dysfunction. Both activation of myocardial oxidative stress and impairment of beta-adrenergic signaling become prominent at the stage of severe LV dysfunction. Myocardial oxidative stress may be involved in the development of beta-adrenergic desensitization.

Adenylyl Cyclases↗

PubMed2004

Acceleration with exercise during head-down bed rest preserves upright exercise responses.

INTRODUCTION: This study was designed to elucidate the effect of short-arm centrifuge-induced artificial gravity with exercise training during ground-based simulated spaceflight, i.e., prolonged head-down bed rest (HDBR), on respiratory and cardiovascular responses to upright exercise. METHODS: There were 10 healthy men who underwent 20 d of -6 degrees HDBR, and were assigned to either a countermeasure (CM) group (n = 5) or a no countermeasure (No-CM) group (n = 5). The subjects in the CM group performed two sessions (20 min each session, 40 min total) of short-arm centrifuge-induced artificial gravity with exercise training in a supine position on alternate days (10 d total) during HDBR. The first session was set at 0.8-1.4 G load at heart level with a constant exercise intensity (60 W), and the second session began with a 0.3 G load at heart level with an interval exercise protocol (40-80% peak oxygen uptake; VO2peak). The measurements of respiratory and cardiovascular responses to incremental exercise were performed pre- and post-HDBR. RESULTS: The 20 d of HDBR increased minute expired ventilation, heart rate, and respiratory exchange ratio and decreased stroke volume during submaximal exercise in the No-CM group, whereas these parameters were unchanged in the CM group. In the No-CM group, VO2peak decreased significantly (47.0 +/- 8.6 to 34.8 +/- 6.8 ml x kg(-1) x min(-1), p < 0.05), whereas VO2peak in the CM group did not show a significant decrease following 20 d of HDBR (47.7 +/- 10.0 to 43.9 +/- 8.9 ml x kg(-1) x min(-1)). These results suggest that short-arm centrifuge-induced artificial gravity with exercise training is effective in maintaining respiratory and cardiovascular responses to upright exercise.

Adolescent↗

PubMed2004

Effect of centrifuge-induced artificial gravity and ergometric exercise on cardiovascular deconditioning, myatrophy, and osteoporosis induced by a -6 degrees head-down bedrest.

We have reported that centrifuge-induced artificial gravity with ergometric exercise could reduce developing cardiovascular deconditioning in humans. In the present study, we examined this load could prevent the myatrophy and osteoporosis induced by head-down bedrest for 20 days. Subjects were ten healthy male volunteers with informed consent. They were requested to lie down at -6 degrees for 20 days, and evaluation for cardiovascular deconditioning, myatrophy, and osteoporosis. As the result, high G-load with low intensity exercise suppressed the orthostatic intolerance and increase in serum osteoporotic marker, whereas low G-load with high intensity ergometric exercise maintained the maximal oxygen intake, heart dimension, and prevented myatrophy. The combination of high/low G-load with low/high intensity exercise will determine the optimal protocol for prevention of cardiovascular deconditioning, myatrophy, and osteoporosis.

Adult↗