RESUMO
A large amount of norepinephrine (NE) released from cardiac sympathetic nerve terminals might accelerate myocardial ischemic injury. Nicorandil (NICO), KATP channel opener, could attenuate cardiac NE release from the sympathetic nerve terminals during ischemia. The present study aimed to investigate the effects of NICO-induced attenuation of cardiac NE release on myocardial ischemia-reperfusion (I/R) injury in rats, by comparison with the effect of cardiac sympathetic denervation on I/R injury.Cardiac interstitial NE (iNE) concentrations were determined using a microdialysis method. Rats were divided into 3 groups; control, NICO, and denervation groups. Cardiac sympathetic denervation was performed by painting 10% phenol on the left ventricular epicardium 7 days before producing ischemia. The left coronary artery was ligated for 30 minutes and then re-perfused for 120 minutes. NICO (50 µg/kg/minute) was infused intravenously starting 20 minutes before the coronary occlusion to the end of the ligation.The infarct size of the left ventricle was smaller in rats treated with NICO than in control rats (20.2 ± 3.0 versus 50.6 ± 14.7%, P < 0.01). Sympathetic denervation also reduced infarct size (28.5 ± 10.4 %, P < 0.01), which was not significantly different from that in the NICO group. At the end of 30-minute ischemia, iNE increased markedly in control rats (0.1 ± 0.1 to 20.6 ± 5.3 × 103 pg/mL), whereas the increase was completely inhibited in denervated rats. NICO markedly attenuated the increase (4.9 ± 3.0 × 103 pg/mL, P < 0.01) during ischemia.NICO-induced attenuation of neural NE release during ischemia might, at least in part, contribute to myocardial protection against I/R injury.
Assuntos
Ventrículos do Coração/inervação , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Nicorandil/farmacologia , Norepinefrina/antagonistas & inibidores , Fibras Simpáticas Pós-Ganglionares/metabolismo , Animais , Modelos Animais de Doenças , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Fibras Simpáticas Pós-Ganglionares/efeitos dos fármacos , Complexo Vitamínico B/farmacologiaRESUMO
Diabetic cardiomyopathy is associated with increased oxidative stress and vascular endothelial dysfunction, which lead to coronary microangiopathy. We tested whether statin-induced redox imbalance improvements could ameliorate diabetic cardiomyopathy and improve coronary microvasculature in streptozotocin-induced diabetes mellitus (DM). Fluvastatin (10 mg/kg/day) or vehicle was orally administered for 12 weeks to rats with or without DM. Myocardial oxidative stress was assessed by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase subunit p22(phox) and gp91(phox) mRNA expression, and myocardial 8-iso-prostaglandin F(2α) (PGF(2α)) levels. Myocardial vascular densities were assessed using anti-CD31 and anti-α-smooth muscle actin (SMA) antibodies. Fluvastatin did not affect blood pressure or plasma cholesterol, but attenuated increased left ventricular (LV) minimum pressure and ameliorated LV systolic dysfunction in DM rats in comparison with vehicle (LV dP/dt, 8.9 ± 1.8 vs 5.4 ± 1.0 × 10(3) mmHg/s, P < 0.05). Myocardial oxidative stress increased in DM, but fluvastatin significantly reduced p22(phox) and gp91(phox) mRNA expression and myocardial PGF(2α) levels. Fluvastatin enhanced myocardial endothelial nitric oxide synthase (eNOS) protein levels and increased eNOS, vascular endothelial growth factor, and hypoxia-inducible factor-1α mRNA expression. CD31-positive cell densities were lower in DM rats than in non-DM rats (28.4 ± 13.2 vs 48.6 ± 4.3/field, P < 0.05) and fluvastatin restored the number (57.8 ± 18.3/field), although there were no significant differences in SMA-positive cell densities between groups. Fluvastatin did not affect cardiac function, oxidative stress, or vessel densities in non-DM rats. These results suggest that beneficial effects of fluvastatin on diabetic cardiomyopathy might result, at least in part, from improving coronary microvasculature through reduction in myocardial oxidative stress and upregulation of angiogenic factor.
Assuntos
Antioxidantes/farmacologia , Vasos Coronários/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Ácidos Graxos Monoinsaturados/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Indóis/farmacologia , Microvasos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Actinas/metabolismo , Animais , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Dinoprostona/análogos & derivados , Dinoprostona/metabolismo , Fluvastatina , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoprostanos/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Microvasos/metabolismo , Microvasos/fisiopatologia , NADPH Oxidase 2 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , RNA Mensageiro/metabolismo , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacosRESUMO
Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.
Assuntos
Vasos Coronários/fisiopatologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Neovascularização Fisiológica , Banho a Vapor , Remodelação Ventricular , Actinas/metabolismo , Análise de Variância , Animais , Fator Natriurético Atrial/genética , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Distribuição de Qui-Quadrado , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hemodinâmica , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/genética , Função Ventricular Esquerda , Pressão VentricularRESUMO
The responses of sympathetic nerve activity to transient stress can be exaggerated in salt-sensitive (SS), hypertensive subjects. Cardiac and renal interstitial norepinephrine (iNE) levels during and after transient hypercapnia were investigated in conscious SS rats. Dahl SS and salt-resistant (SR) 6-wk-old rats were fed a high-salt diet, and at 12 wk iNE levels in the heart and kidney were determined using microdialysis with probes inserted in the left ventricular (LV) wall and kidney. A telemetry system determined blood pressure and heart rate (HR) in separate animals. After recovery from the operation, data were collected before, during, and after exposure to normoxic 10% CO(2) for 25 min under unanesthetized conditions. The plasma NE concentrations at baseline did not differ between the two strains. Both cardiac and renal iNE levels were much higher in SS rats than in SR rats at baseline as well as during hypercapnic stress. After stress, the markedly increased iNE levels of SS rats were prolonged in the LV as well as in the kidney. During hypercapnic stress, HR decreased in both SS and SR rats, while sudden increases in HR immediately after the withdrawal from stress were followed by its slower reduction in SS rats compared with SR rats. In conclusion, transient hypercapnic stress causes exaggerated and prolonged elevation of iNE levels in the heart as well as in kidneys of SS animals.
Assuntos
Hipercapnia/metabolismo , Hipertensão/metabolismo , Rim/metabolismo , Miocárdio/metabolismo , Norepinefrina/metabolismo , Animais , Pressão Sanguínea/fisiologia , Estado de Consciência/fisiologia , Modelos Animais de Doenças , Frequência Cardíaca/fisiologia , Microdiálise , Ratos , Ratos Endogâmicos Dahl , Taxa Respiratória/fisiologia , Inconsciência/metabolismo , Inconsciência/fisiopatologiaRESUMO
It remains unclear whether atherosclerosis in one vascular bed progresses in parallel with that in other vascular beds. We investigated serial changes in vessel wall areas (VWAs) in various vessels over 2 years of follow-up. Vessel wall areas in the thoracic descending aorta (TDA), common carotid artery (CCA), right (RCA), and left main trunk (LMT) of coronary artery were determined in 52 patients with coronary artery disease (CAD) using 64-slice multidetector computed tomography. Plasma levels of high-sensitivity CRP (hs-CRP) and matrix metalloproteinase (MMP)-9, as well as urinary 8-iso-prostaglandin F2α (PGF2α) were determined at the baseline. After the follow-up period, plaque progression in a specific vessel did not parallel that of other vessels, although changes in TDA-VWAs were weakly correlated with those of LMT-VWAs. Basal levels of hs-CRP, MMP-9, and PGF2α did not predict progression or regression of VWAs in any vessels. Multivariate analyses showed that LDL-cholesterol < 100 mg/dl and use of statin emerged as predictors of regressing VWAs in TDA (p < 0.05 and p < 0.05, respectively) and LMT (p < 0.05 and p = 0.13, respectively). Changes in soft plaques over 2 years paralleled those of VWAs in both coronary arteries. In conclusion, the progression or regression of atherosclerotic plaques is inhomogeneous among the vascular beds of patients with CAD.
Assuntos
Aorta Torácica/patologia , Doenças da Aorta/patologia , Aterosclerose/patologia , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/patologia , Doença da Artéria Coronariana/patologia , Idoso , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/sangue , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/tratamento farmacológico , Doenças da Aorta/urina , Aortografia/métodos , Aterosclerose/sangue , Aterosclerose/diagnóstico por imagem , Aterosclerose/tratamento farmacológico , Aterosclerose/urina , Biomarcadores/sangue , Biomarcadores/urina , Proteína C-Reativa/análise , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/urina , Artéria Carótida Primitiva/diagnóstico por imagem , LDL-Colesterol/sangue , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/urina , Dinoprosta/análogos & derivados , Dinoprosta/urina , Progressão da Doença , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Japão , Modelos Logísticos , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of long-term treatment with fluvastatin (FL) on myocardial oxidative stress and cardiac sympathetic neural function were investigated in diabetic rats. METHODS AND RESULTS: FL (10 mg . kg(-1) . day(-1), DM-FL) or vehicle (DM-VE) was orally administered for 2 weeks to streptozotocin-induced DM rats. Cardiac oxidative stress was determined by myocardial 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) and NADPH oxidase subunit p22(phox) mRNA expression. Sympathetic neural function was quantified by autoradiography using (131)I- and (125)I-metaiodobenzylguanidine (MIBG). FL did not affect plasma glucose levels but remarkably decreased PGF(2alpha) levels compared with DM-VE rats (13.8+/-9.2 vs 175.0+/-93.9 ng/g tissue), although PGF(2alpha) levels were below the detection limit in non-DM rats. FL significantly reduced myocardial p22(phox) mRNA expression. Cardiac (131)I-MIBG uptake was lower in DM-VE rats than in non-DM rats, but the decrease was attenuated in DM-FL rats (1.31+/-0.08, 1.88+/-0.22, and 1.58+/-0.18 %kg dose/g, respectively, P<0.01). Cardiac MIBG clearance was not affected by the induction of DM or by FL, indicating that the reduced MIBG uptake in DM rats might result from impaired neural function. CONCLUSIONS: FL ameliorates cardiac sympathetic neural dysfunction in DM rats in association with attenuation of increased myocardial oxidative stress.
Assuntos
Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/tratamento farmacológico , Ácidos Graxos Monoinsaturados/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Indóis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , 3-Iodobenzilguanidina , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Neuropatias Diabéticas/diagnóstico por imagem , Neuropatias Diabéticas/metabolismo , Dinoprosta/metabolismo , Fluvastatina , Coração/diagnóstico por imagem , Radioisótopos do Iodo , Masculino , Miocárdio/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , RNA Mensageiro/metabolismo , Cintilografia , Ratos , Ratos Wistar , Sistema Nervoso Simpático/diagnóstico por imagem , Sistema Nervoso Simpático/metabolismo , Triglicerídeos/sangueRESUMO
Use of mobile phones has become a standard reality of everyday living for many people worldwide, including medical professionals, as data sharing has drastically helped to improve quality of care. This increase in the use of mobile phones within hospitals and medical facilities has raised concern regarding the influence of radio waves on medical equipment. Although comprehensive studies have examined the effects of electromagnetic interference from 2G wireless communication and personal digital cellular systems on medical equipment, similar studies on more recent wireless technologies such as Long Term Evolution, wideband code division multiple access, and high-speed uplink access have yet to be published. Numerous tests targeting current wireless technologies were conducted between December 2012 and March 2013 in an anechoic chamber, shielded from external radio signals, with a dipole antenna to assess the effects of smartphone interference on several types of medical equipment. The interference produced by electromagnetic waves across five frequency bands from four telecommunication standards was assessed on 49 components from 22 pieces of medical equipment. Of the 22 pieces of medical equipment tested, 13 experienced interference at maximum transmission power. In contrast, at minimum transmission power, the maximum interference distance varied from 2 to 5 cm for different wireless devices. Four machines were affected at the minimum transmission power, and the maximum interference distance at the maximum transmission power was 38 cm. Results show that the interference from smartphones on medical equipment is very controllable.
Assuntos
Artefatos , Eletrônica Médica/estatística & dados numéricos , Falha de Equipamento/estatística & dados numéricos , Equipamentos e Provisões/estatística & dados numéricos , Smartphone/instrumentação , Smartphone/estatística & dados numéricos , Eletrônica Médica/classificação , Eletrônica Médica/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento/estatística & dados numéricos , Japão , Doses de Radiação , Ondas de Rádio , Smartphone/classificação , Inquéritos e QuestionáriosRESUMO
UNLABELLED: We investigated whether changes in myocardial uptake of fatty acid tracer after reperfusion following transient myocardial ischemia were closely related to alterations in intracellular fatty acid oxidation. METHODS: Using a fatty acid tracer of (131)I- and (125)I-labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA), the myocardial uptake and metabolites were determined by dual-tracer autoradiography and thin-layer chromatography in rats 3 or 14 d after reperfusion following 5 or 15 min of ischemia induced by coronary artery ligation. RESULTS: 9MPA metabolites processed via beta-oxidation were lower in the ischemic region (IR) than in non-IR 3 d after 5 min of ischemia, despite no reduction of tracer uptake in IR. Oxidation of 9MPA was recovered 14 d after 15 min of ischemia in association with normalization of tracer uptake in IR, whereas both uptake and oxidation of 9MPA were markedly impaired 3 d after 15 min of ischemia, accompanied by slow clearance of myocardial tracer. CONCLUSION: Normal uptake of fatty acid tracer early after reperfusion does not always imply preserved intracellular fatty acid oxidation. However, reduction of tracer uptake might reflect impaired fatty acid oxidation.
Assuntos
Ácidos Graxos/farmacocinética , Coração/diagnóstico por imagem , Iodobenzenos/farmacocinética , Miocárdio/metabolismo , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/metabolismo , Animais , Autorradiografia/métodos , Ácidos Graxos/metabolismo , Taxa de Depuração Metabólica , Oxirredução , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos WistarRESUMO
The time-dependent effects of daily dosing of IGF-I (1.21 mg/g) on the linear growth of the femur were investigated in mice. The femoral length and volume and the number of osteoclasts were significantly greater after IGF-I injection as compared to the non-injected control, suggesting that the IGF-I imbalance might cause a quick turnover cycle of the bone resulting in the altered femoral modeling.
Assuntos
Remodelação Óssea/efeitos dos fármacos , Fêmur/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fêmur/citologia , Fator de Crescimento Insulin-Like I/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/citologia , Estimulação Química , Fatores de TempoRESUMO
Alendronate, one of the bisphosphonates, is known to have an inhibitory effect on bone resorption. The purpose of this study was to investigate the effects of alendronate on ectopic bone graft resorption and to determine the optimal dose in the mouse. The grafted bone in the control group disappeared due to resorption by osteoclasts within 5 weeks. In the experimental groups, the area of bone tissue decreased by only 20-40% at 5 weeks post-operatively. At 8 and 9 weeks after surgery, the decreased area of bone structure was significantly less in all the 10(-4) M injected alendronate-immersed groups than in the 10(-4) M non-injected alendronate-immersed. At 9 weeks after surgery, the number of osteoclasts were significantly less in the 10(-4) M injected alendronate-treated groups than in the 10(-4) M non-injected alendronate-treated groups. These results suggest that alendronate inhibits resorption of ectopic bone graft at concentrations of 10(-4) and 10(-6) M.
Assuntos
Alendronato/farmacologia , Reabsorção Óssea , Transplante Ósseo/patologia , Diferenciação Celular/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Animais , Histocitoquímica , Camundongos , Osteoclastos/citologiaRESUMO
AIM: Epicardial adipose tissue (EAT) is a pathogenic fat depot that may be associated with coronary atherosclerosis and cardiovascular events. Because eicosapentaenoic acid (EPA) has been reported to exert cardiovascular protective effects, we aimed to assess the effects of EPA on the volume of visceral adipose tissue, including EAT and abdominal visceral adipose tissue (AVAT), using multislice computed tomography (CT). METHODS: In 30 patients with coronary artery diseases (9 women; mean age, 67.2 ± 5.4 years), EAT and AVAT volumes were compared between the control group (n=15, conventional therapy) and the EPA group (n=15, conventional therapy plus purified EPA 1800 mg/day) during a six-month period. EAT was defined as any pixel that had CT attenuation of -150 to -30 Hounsfield units (HU) within the pericardial sac. RESULTS: After the six-month follow-up, the serum EPA level increased from 59.9 ± 18.8 to 177.2 ± 3.3 µg/mL in the EPA group (p<0.01), but no increase was noted in the control group. Similarly, the EPA/arachidonic acid (AA) ratio increased from 0.39 ± 0.12 to 1.22 ± 0.28 in the EPA group (p<0.01), with no significant increase in the control group. The AVAT and EAT volumes decreased in the EPA group but were unchanged in the control group (AVAT, -11.6 ± 17.0 vs. +8.8 ± 13.6 cm(2), p<0.01; EAT, -7.3 ± 8.3 vs. +8.7 ± 8.8 cm(3), p<0.01). Moreover, the change in the AVAT volume negatively correlated with the change in EPA (r=-0.58, p<0.01) and EPA/AA levels (r=-0.53, p<0.01). A similar negative correlation in these parameters was also observed for the EAT volume. CONCLUSIONS: Oral intake of purified EPA appears to be associated with reductions in EAT and AVAT volumes.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Ácido Eicosapentaenoico/uso terapêutico , Gordura Intra-Abdominal/efeitos dos fármacos , Pericárdio/efeitos dos fármacos , Idoso , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/farmacologia , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Masculino , Pessoa de Meia-Idade , Pericárdio/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Repeated low-temperature sauna (Waon) therapy relieves ischemic symptoms in patients with peripheral arterial disease. We investigated whether Waon therapy could improve myocardial perfusion in patients with ischemia related to chronic total occlusion (CTO) of coronary arteries. METHODS: Twenty-four patients who had ischemia in the CTO-related area were examined. The severity of ischemia was quantified by thallium-201 myocardial perfusion scintigraphy with adenosine. The Waon group (n=16) was treated daily for three weeks with a 60 °C far infrared-ray dry sauna bath for 15 min and then kept in a bed covered with blankets for 30 min. The control group (n=8) underwent myocardial perfusion scintigraphy twice with a three-week interval. RESULTS: In the control group, neither summed stress score (SSS) nor summed difference score (SDS) of myocardial scintigraphy changed. However, Waon therapy improved both SSS (16 ± 7 to 9 ± 6, p<0.01) and SDS (7 ± 4 to 3 ± 2, p<0.01), and the improvement was greater in patients with higher SSS and SDS scores at the baseline. Waon therapy extended treadmill exercise time (430 ± 185 to 511 ± 192s, p<0.01) and improved flow-mediated dilation of the brachial artery (4.1 ± 1.3 to 5.9 ± 1.8%, p<0.05), but tended to decrease the number of circulating CD34-positive bone marrow-derived cells. CONCLUSIONS: Waon therapy improves CTO-related myocardial ischemia in association with improvement of vascular endothelial function. This therapy could be a complementary and alternative tool in patients with severe coronary lesions not suitable for coronary intervention.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Circulação Coronária/fisiologia , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/terapia , Banho a Vapor/métodos , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/fisiologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Vasodilatação/fisiologiaRESUMO
Repeated sauna treatment, known as Waon therapy, has been shown to improve cardiac function as well as exercise tolerance in patients with chronic heart failure. However, the underlying mechanisms of this therapy regarding these improvements remain to be elucidated. Forty-one patients with chronic heart failure (mean age 68.3 ± 13.5 years old) underwent Waon therapy 5 times a week for 3 weeks. Before and after treatment, a number of assessments were performed in all subjects: 6-minute walk test, echocardiography, determination of neurohumoral factors and number of circulating CD34(+) cells, and a flow-mediated dilation (FMD) test of endothelial function. Cardiopulmonary exercise testing was also performed in 20 patients. Waon therapy increased the left ventricular ejection fraction (from 30.4 ± 12.6% to 32.5% ± 12.8%, p = 0.023) and reduced plasma levels of norepinephrine (from 400 ± 258 to 300 ± 187 pg/ml, p = 0.015) and brain natriuretic peptide (from 550 ± 510 to 416 ± 431 pg/ml, p = 0.035). Waon therapy increased the 6-minute walk distance (from 337 ± 120 to 379 ± 126 m, p <0.001) in association with an improvement in FMD (from 3.5 ± 2.3% to 5.5% ± 2.7%, p <0.001) and an increase in the number of circulating CD34(+) cells (p = 0.025). Changes in 6-minute walk distance were correlated positively with those in the left ventricular ejection fraction and FMD and negatively with those in plasma levels of norepinephrine and brain natriuretic peptide levels. A multivariate analysis revealed that an increase in FMD was the only independent determinant of 6-minute walk distance improvement. Finally, Waon therapy significantly increased peak Vo(2), and this increase was also correlated with changes in FMD. In conclusion, repeated sauna therapy in patients with chronic heart failure improves exercise tolerance in association with improvement in endothelial function.
Assuntos
Endotélio Vascular/fisiopatologia , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/terapia , Hipertermia Induzida/métodos , Banho a Vapor , Vasodilatação/fisiologia , Idoso , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Progressão da Doença , Ecocardiografia , Teste de Esforço , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Both statins and renin-angiotensin system (RAS) inhibitors inhibit atherosclerotic progression and reduce cardiovascular events. However, it remains unclear whether combination therapy of RAS inhibitor with statin could inhibit plaque progression more than statin alone. METHODS: Using 64 multislice computed tomography, vessel wall areas (VWAs) and total vascular areas of the left main trunk (LMT) and proximal right coronary artery (RCA) and the thoracic descending aorta (TDA) were determined in patients with coronary artery disease before and after 2.0-year treatment with atorvastatin and candesartan (n=20) or with atorvastatin alone (n=16), although these patients had been treated with the combination therapy or statin alone at the study enrollment. Plasma levels of high sensitive C-reactive protein, matrix metalloproteinase-9, and urinary 8-iso-prostaglandin F2α were determined at the baseline. RESULTS: There were no significant differences in low-density lipoprotein and high-density lipoprotein cholesterol, C-reactive protein, matrix metalloproteinase-9, or urinary 8-iso-prostaglandin F2α levels between the two groups. Two years later, total vascular areas of TDA and RCA increased significantly in the atorvastatin group but not in the combination group. Moreover, increases in VWAs were less in the combination group than in the atorvastatin group in TDA (3.6 ± 23.1 vs. 28.6 ± 25.5 mm, P=0.004), RCA (-1.6 ±1.6 vs. 0.6 ± 2.5 mm, P=0.005), and left main trunk (-0.9 ± 3.5 vs. 1.3 ± 2.4 mm, P=0.095). Biomarker levels at the baseline did not affect the progression of VWA. CONCLUSION: Combination therapy of RAS inhibitor with statin is more effective than statin alone in inhibiting atherosclerotic progression of coronary arteries and the aorta in patients with coronary artery disease.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Benzimidazóis/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Pirróis/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Aterosclerose/sangue , Aterosclerose/patologia , Atorvastatina , Biomarcadores/sangue , Biomarcadores/urina , Compostos de Bifenilo , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Dinoprosta/urina , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Myocardial perfusion imaging shows various patterns in patients with non-ischemic dilated cardiomyopathy (DCM). However, influences of regional abnormalities of myocardial perfusion or ventricular wall motion on prognosis in DCM patients remains to be clarified. Accordingly, we investigated a relation between myocardial perfusion patterns and long-term prognosis in DCM patients. METHODS AND RESULTS: Sixty-two patients were divided into 2 groups according to patterns of (99m)Tc-Tetrofosmin scintigraphy, i.e. large focal defects (focal) and minimally impaired perfusion or multiple small defects (non-focal). There were no differences between the 2 groups in left ventricular (LV) end-diastolic dimensions (63.4 ± 9.1 and 63.8.4 ± 7.5mm, respectively) and LV ejection fraction (30.3 ± 9.2 and 27.9 ± 7.8%, respectively), indicating LV systolic dysfunction was comparable between the groups. The focal group had a higher prevalence of brain natriuretic peptide ⧠200 ng/dl and plasma norepinephrine ⧠500 pg/ml than the non-focal group (p<0.05), and had longer QRS durations (p<0.05). The focal group had non-sustained ventricular tachycardia (VT) (p<0.05) on 24-h electrocardiogram recording and a history of VT/ventricular fibrillation more frequently (p<0.05), and had higher New York Heart Association functional class than the non-focal group (p<0.05). The mortality was significantly higher in the focal group (56.0%) than in the non-focal group (28.6%) and the survival curves revealed worse prognosis in the focal group during a follow-up period of 5.3 ± 2.8 years. CONCLUSIONS: Non-ischemic DCM patients with focal defects are accompanied by more advanced heart failure and poor prognosis compared to those with minimally impaired perfusion or multiple small defects, despite comparable LV systolic dysfunction.
Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Imagem de Perfusão do Miocárdio , Adulto , Idoso , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Ischemic preconditioning (IPC) reduced myocardial ATP depletion during sustained ischemia and has a powerful protective effect on the myocardium. The purpose of the present study was to clarify the effects of IPC on myocardial accumulation of fatty acid (FA) tracer and its intracellular metabolism. METHODS: Myocardial ischemia-reperfusion (MI-R) injury was induced by the left coronary artery ligation for 15 min followed by reperfusion in Wistar rats. IPC was achieved with a single cycle of 5-minute coronary ligation followed by 5-minute reperfusion before MI-R. Three days after ischemia-reperfusion, FA metabolism was evaluated in rats with or without IPC using (131)I- and (125)I-15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA) and thin-layer chromatography. RESULTS: IPC attenuated a reduction of 9MPA accumulation in ischemic region (IR). The metabolite fraction of 9MPA including both early and late metabolites was less in IR as compared to non-IR in rats without IPC. IPC increased the final metabolic product of 9MPA processed via alpha- and beta-oxidation in both IR and non-IR. CONCLUSIONS: IPC accelerated fatty acid oxidation in both IR and non-IR. This alteration in fatty acid metabolism would inhibit an intracellular accumulation of detrimental fatty acid metabolites.
Assuntos
Trifosfato de Adenosina/metabolismo , Ácidos Graxos/metabolismo , Iodobenzenos/metabolismo , Miocárdio/metabolismo , Animais , Autorradiografia , Cromatografia em Camada Fina , Processamento de Imagem Assistida por Computador , Precondicionamento Isquêmico Miocárdico , Oxirredução , Ratos , Ratos WistarRESUMO
Danon disease is an X-linked dominant multisystem disorder that includes hypertrophic cardiomyopathy with skeletal myopathy, and results from mutations in the gene encoding the lysosome-associated membrane protein-2 (LAMP-2). To date, over 20 different mutations in LAMP2 have been identified. Three members of a family, a male proband (18 years old) and 2 sisters (15 and 20 years old) were studied. Their mother had been diagnosed with dilated cardiomyopathy at the age of 39 years, and died from advanced heart failure at the age of 43 years. The proband developed marked concentric hypertrophy at the age of 5 years and DNA analyses revealed a novel hemizygous frameshift mutation (c.573delA) in exon 5. The 2 affected sisters were also heterozygous for the same mutation. Functional analyses of this novel LAMP2 mutation are mandatory.
Assuntos
Cardiomiopatia Hipertrófica/genética , Mutação da Fase de Leitura/genética , Doença de Depósito de Glicogênio Tipo IIb/genética , Proteínas de Membrana Lisossomal/genética , Adolescente , Cardiomiopatia Hipertrófica/diagnóstico , Ecocardiografia , Eletrocardiografia , Doença de Depósito de Glicogênio Tipo IIb/diagnóstico , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Proteína 2 de Membrana Associada ao Lisossomo , Masculino , LinhagemRESUMO
The beneficial effects of statins in patients with coronary artery disease (CAD) may be balanced by concerns that statins can depress production of ubiquinone (CoQ10), which serves as a component of mitochondrial energy production and an antioxidant. Accordingly, the effects of atorvastatin (ATO)-induced changes in plasma CoQ10 on BNP and oxidative stress were investigated. In 29 patients with CAD, the plasma levels of CoQ10 and BNP and urinary excretion of 8-iso-prostaglandin F2alpha (8-iso-PGF) were determined before and after 3-month treatment with ATO. Ten patients had received pravastatin and 10 patients fluvastatin, while 9 patients had not received any statin before ATO. There was a linear correlation between ATO-induced changes in total cholesterol and CoQ10 (r = 0.632, P < 0.01), and an inverse correlation between ATO-induced changes in CoQ10 and BNP (r = -0.497, P < 0.01). There was no significant correlation between ATO-induced changes in CoQ10 and 8-iso-PGF. Multivariate analysis revealed that ATO-induced decreases in plasma CoQ10 were significantly associated with increasing BNP levels. In conclusion, long-term treatment with ATO might increase plasma levels of BNP in patients with CAD when it is accompanied by a greater reduction in plasma CoQ10. However, ATO-induced decreases in CoQ10 might not increase oxidative stress.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Pirróis/uso terapêutico , Ubiquinona/análogos & derivados , Idoso , Atorvastatina , Cromatografia Líquida de Alta Pressão , Doença da Artéria Coronariana/sangue , Relação Dose-Resposta a Droga , Seguimentos , Ácidos Heptanoicos/administração & dosagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Imunoensaio , Peptídeo Natriurético Encefálico/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pirróis/administração & dosagem , Resultado do Tratamento , Ubiquinona/sangue , Ubiquinona/efeitos dos fármacosRESUMO
BACKGROUND: The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. METHODS AND RESULTS: Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1 +/- 4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05) compared with rats without the pretreatment. CONCLUSION: A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.
Assuntos
Angina Pectoris/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Sistema Nervoso Simpático/lesões , Sistema Nervoso Simpático/fisiopatologia , 3-Iodobenzilguanidina/administração & dosagem , Idoso , Angina Pectoris/complicações , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/metabolismo , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/metabolismo , Norepinefrina/metabolismo , Radiografia , Compostos Radiofarmacêuticos/administração & dosagem , Ratos , Sistema Nervoso Simpático/diagnóstico por imagem , Sistema Nervoso Simpático/metabolismo , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: Three-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are known to attenuate myocardial ischemia-reperfusion (IR) injury. Fluvastatin (FV) has a potent free radical scavenging action, but it is unclear whether the timing of FV administration could affect its cardioprotective effect or if the antioxidant property of FV might attenuate IR injury. METHODS AND RESULTS: IR was induced in rats by left coronary artery occlusion for 30 min followed by 24-h reperfusion. The rats were divided into 4 groups: oral FV group (10 mg/kg per day for 2 weeks before ischemia); iv, FV group (10 mg/kg) before ischemia; iv, FV group (10 mg/kg) before reperfusion; and control group. Oxidative stress was evaluated by myocardial 8-hydroxydeoxyguanosine (8-OHdG) content. The area at risk did not different among the 4 groups. Pretreatment with FV for 2 weeks significantly reduced the infarct size by 28% as compared with the control group, but FV administered just before ischemia or reperfusion did not. Myocardial 8-OHdG content was not affected by FV. The infarct-sparing effect of FV was completely abolished by N(omega)-nitro-l-arginine methyl ester or wortmannin. CONCLUSIONS: The present results indicate that pretreatment with FV, but not just before ischemia or reperfusion, attenuates IR injury primarily through the nitric oxide pathway, not through its antioxidant property.