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It has been reported that a single-dose cardioplegia interval is useful, but the safe interval doses are not clear. We aimed to investigate the impact of the cardioplegia interval on myocardial protection using the modified St. Thomas solution. We included consecutive isolated minimally invasive mitral valvuloplasty procedures (n = 229) performed at a hospital and medical center from January 2014 to December 2020. We compared postoperative peak creatine kinase MB and creatine kinase levels and other indicators between the short (Group S, n = 135; maximum myocardial protection interval <60 minutes) and long (Group L, n = 94; maximum myocardial protection interval ≥60 minutes) interval groups. Propensity score matching was used to adjust for confounders between the two groups. After propensity score matching, Groups S and L contained 47 patients each. Groups S and L did not differ significantly in peak creatine kinase MB (45.8 ± 26.3 IU/L and 41.5 ± 27.9 IU/L, respectively; p = .441) and creatine kinase levels (1,133 ± 567 IU/L and 1,100 ± 916 IU/L, respectively; p = .837) after admission to the intensive care unit on the day of surgery based on propensity score matching. In multivariate analysis, a cardioplegia dosing interval ≥60 minutes was not significantly associated with the maximum creatine kinase MB level after admission to the intensive care unit on the day of surgery (p = .354; 95% confidence interval: -1.67 to 4.65). Using the antegrade modified St. Thomas solution, the long interval dose method is useful and safe in minimally invasive mitral valvuloplasty.
Assuntos
Soluções Cardioplégicas , Valva Mitral , Soluções Cardioplégicas/uso terapêutico , Creatina Quinase Forma MB , Parada Cardíaca Induzida/métodos , Humanos , Valva Mitral/cirurgia , Cloreto de PotássioRESUMO
BACKGROUND: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients.MethodsâandâResults:Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m2), and cardiac index (CI; L/min/m2). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group. CONCLUSIONS: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.
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Compostos Benzidrílicos/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Exercício Físico , Glucosídeos/administração & dosagem , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/epidemiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Peak oxygen uptake (VO2), evaluated as exercise tolerance, is a strong predictor of life prognosis regardless of health condition. Several previous studies have reported that peak VO2 is higher in those with a greater decrease in muscle oxygen saturation (SmO2) in the active muscles during incremental exercise. However, the skeletal muscle characteristics of individuals exhibiting a greater decrease in SmO2 during active muscle engagement in incremental exercise remain unclear. This study aimed to clarify the relationship among muscle strength, muscle endurance, and skeletal muscle oxygenation dynamics in active leg muscles during incremental exercise. Twenty-four healthy young men were included and categorized into the non-moderate-to-high muscular strength and endurance group (those with low leg muscle strength, endurance, or both; n = 11) and the moderate-to-high muscular strength and endurance group (those with both moderate-to-high leg muscle strength and endurance; n = 13). All participants underwent cardiopulmonary exercise testing combined with near-infrared spectroscopy to assess whole-body peak VO2 and the change in SmO2 at the lateral vastus lateralis from rest to each exercise stage as skeletal muscle oxygenation dynamics. A linear mixed-effects model, with the change in SmO2 from rest to each stage as the dependent variable, individual participants as random effects, and group and exercise load as fixed effects, revealed significant main effects for both group (P = 0.001) and exercise load (P < 0.001) as well as a significant interaction between the two factors (P < 0.001). Furthermore, multiple-comparison test results showed that the change in SmO2 from rest to 40%-100% peak VO2 was significantly higher in the moderate-to-high muscular strength and endurance group than in the non-moderate-to-high muscular strength and endurance group. Maintaining both muscle strength and endurance at moderate or higher levels contributes to high skeletal muscle oxygenation dynamics (i.e., greater decrease in SmO2) during moderate- or high-intensity exercise.
Assuntos
Força Muscular , Músculo Esquelético , Consumo de Oxigênio , Resistência Física , Humanos , Masculino , Força Muscular/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Consumo de Oxigênio/fisiologia , Adulto Jovem , Resistência Física/fisiologia , Adulto , Exercício Físico/fisiologia , Teste de Esforço , Espectroscopia de Luz Próxima ao Infravermelho , Oxigênio/metabolismo , Saturação de Oxigênio/fisiologiaRESUMO
BACKGROUND: Nocturnal and early morning hypertension are both significant risk factors for cardiovascular events. It remains unclear whether anxiety disorder affects nocturnal blood pressure (BP), early morning BP, or BP pattern in hypertensive patients. METHODS AND RESULTS: One hundred and twenty consecutive hypertensive outpatients (77 men and 43 women; mean age, 66±11 years) were divided into 2 groups based on Hospital Anxiety and Depression Scale (HADS) score: a control group (n=78; HADS ≤10) and an anxiety group (42 patients; HADS ≥11). Nocturnal BP, early morning BP, morning BP surge (defined as BP rise ≥50 mmHg), and BP pattern (extreme-dipper/dipper/non-dipper/riser) were measured on ambulatory BP monitoring. Clinical characteristics and BP were also evaluated at physician check-up. There was no significant difference between the 2 groups for BP check-up, but nocturnal and early morning BP were significantly higher in the anxiety group (142±16 mmHg and 152±21 mmHg) than in the control group (126±14 mmHg and 141±18 mmHg). With regard to patients with morning BP surge, nocturnal and early morning BP were also significantly higher in the anxiety group. The relative risk of existing anxiety disorders in riser-type hypertension was 4.48-fold higher (95% confidence interval: 1.58-12.74; P<0.005) than in dipper-type hypertension. CONCLUSIONS: Anxiety disorder is associated with nocturnal and early morning hypertension, and may be a risk factor for cardiovascular events.
Assuntos
Transtornos de Ansiedade/epidemiologia , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Ritmo Circadiano , Hipertensão/diagnóstico , Idoso , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Escalas de Graduação Psiquiátrica , Medição de Risco , Fatores de Risco , Transtornos do Sono-Vigília/epidemiologia , Fatores de TempoRESUMO
OBJECTIVE: Preoperative performance status is an important factor in thoracic surgery, but little is known about the effect of preoperative physical activity (PA) on the postoperative course. This study investigated the associations between preoperative PA and postoperative complications and clinical outcomes of lung cancer surgery. METHODS: This prospective observational study included patients who underwent surgery for lung cancer at a single institution. PA was measured before hospitalization for 5 consecutive days and then after surgery until hospital discharge. The daily step count and time spent performing moderate intensity activity (> 3 metabolic equivalents) were measured with an accelerometer. We examined the correlations between PA and preoperative pulmonary function and physical fitness, and examined the relationship between postoperative complication and PA. Finally, a multivariate analysis was performed with pre-hospital PA as the dependent variable. RESULTS: Forty-two patients were analyzed. Univariate analysis found no correlation between pre-hospital PA and preoperative pulmonary function, but found significant positive correlations between pre-hospital PA and time spent performing moderate intensity activity, in-hospital PA, preoperative 6-minute walk distance, and maximum gait speed (r > 0.5, p < 0.01). The nine patients who developed postoperative complications had significantly lower pre-hospital and postoperative step count than the patients with no complication (p = 0.04). Multiple regression analysis showed that pre-hospital PA was significantly associated with time spent performing moderate intensity activity, maximum gait speed, and postoperative complication. CONCLUSIONS: Evaluation of pre-hospital PA is useful in predicting the postoperative course after lung cancer surgery.
RESUMO
OBJECTIVES: In the field of exercise physiology, there has been great interest in exploring circulating microRNAs (miRs) as potential biomarkers. However, it remains to be determined whether circulating miRs reflect cardiorespiratory fitness. The aim of this study was to investigate the association between circulating levels of specific miRs and cardiorespiratory fitness evaluated by cardiopulmonary exercise testing (CPET) after acute myocardial infarction (MI). METHODS: Twenty patients who had had an acute MI were included. All patients underwent CPET in the convalescent phase. Quantitative real-time polymerase chain reaction analyses for miR-181 members (a/b/c) and miR-484 were performed to determine the expression levels in the peripheral blood of the included patients and healthy control subjects (n=5). RESULTS: Post-MI patients showed impaired exercise tolerance and ventilatory efficiency in CPET analysis. Compared with controls, circulating levels of miR-181a and 181c were gradually and significantly elevated through the 1st to 7th days after acute MI, whereas miR-181b and miR-484 were not. Circulating miR levels did not correlate with clinical or echocardiographic parameters. However, circulating levels of miR-181c and miR-484 on the 7th day showed significant positive correlations with the anaerobic threshold and peak oxygen consumption from CPET analysis. Moreover, miR-181c levels were inversely associated with the ventilatory inefficiency index. Patients with high exercise capacity after MI showed significantly higher expressions of circulating miR-181c and miR-484 than those with low exercise capacity. CONCLUSIONS: The results of this pilot study suggest that circulating levels of miR-181c and miR-484 after acute MI may be predictive biomarkers of post-MI cardiorespiratory fitness.
RESUMO
Sleep disordered breathing (SDB) was more prevalent in adolescent athletes than expected, and several potential warning signs related to autonomic nerve activity appeared in SDB athletes. SDB screening may prevent associated downstream risks in the future. http://ow.ly/GQqK30nGm8r.
RESUMO
Carboxylesterase 1 (CES1) is involved in metabolic activation of a variety of prodrugs into active derivatives and plays an important role in pharmacokinetics. We previously reported that a single nucleotide polymorphism (SNP), -816A/C of the CES1A2 gene associates with the responsiveness to an angiotensin-converting enzyme (ACE) inhibitor, imidapril, whose activity is achieved by CES1. To identify relevant functional polymorphisms, we re-sequenced the CES1A2 promoter region ( approximately 1kb) in 100 Japanese hypertensive patients. Altogether 10 SNPs and one insertion/deletion (I/D) were identified, among which seven SNPs and one I/D residing between -62 and -32 were in almost complete linkage disequilibrium (D'=1.00, r2=0.97). They consisted a minor and a major haplotype, the allele frequencies of which were 22% and 74%, respectively. The minor haplotype possessed two putative Sp1 binding sites while the major haplotype did not have any Sp1 binding site. The minor haplotype had a higher transcription and Sp1 binding activities than the major haplotype, invitro. The original -816A/C was in high linkage disequilibrium with these haplotypes (D'=0.92, r2=0.85), and well agreed with the efficacy of imidapril medication. These results suggest that the Sp1 binding site variation in the CES1A2 promoter is functional, and are good candidates for the pharmacogenetic studies of CES1-activated drugs.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Anti-Hipertensivos/farmacocinética , Carboxilesterase/genética , Imidazolidinas/farmacocinética , Polimorfismo de Nucleotídeo Único , Fator de Transcrição Sp1/metabolismo , Sequência de Aminoácidos , Povo Asiático/genética , Sequência de Bases , Sítios de Ligação , Carboxilesterase/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Dados de Sequência Molecular , Regiões Promotoras GenéticasRESUMO
BACKGROUND: Constrictive remodeling is thought to be more important than neointimal formation in coronary restenosis after balloon angioplasty. The inhibition of Rho-kinase prevents neointimal proliferation, but now this inhibition that affects constrictive remodeling remains unknown. To explore this issue further, we investigated whether a specific Rho-kinase inhibitor, Y-27632, could suppress restenosis after coronary balloon angioplasty in a porcine model. METHODS: Balloon angioplasty with local administration of Y-27632 (Y group) or vehicle (C group) was performed at 2 and 3 weeks after overstretch injury in a porcine coronary artery. Quantitative coronary angiography (QCA) and quantitative coronary ultrasound (QCU) were performed to assess the coronary lesion segment. A morphometrical analysis was performed in a histological study. Proliferative cells and p27(Kip1)-positive cells were evaluated in the arterial wall using immunohistochemistry. RESULTS: QCA and QCU demonstrated that the minimal lumen diameter and minimal lumen area were greater, and % stenosis was less in the Y group than in the C group. The QCU analysis also revealed a significant inhibition in the increase of the intimal area and a prevention of constrictive remodeling by Y-27632. In the histological study, the intimal, adventitial and collagen areas were significantly smaller in the Y group than in the C group. The Y group also exhibited significantly less proliferative activity and a significantly higher percentage of cells expressing p27(Kip1) in the arterial wall. CONCLUSION: Local delivery of Y-27632 suppressed constrictive remodeling as well as neointimal formation after coronary balloon angioplasty in pigs.
Assuntos
Amidas/farmacologia , Angioplastia Coronária com Balão , Reestenose Coronária/enzimologia , Reestenose Coronária/prevenção & controle , Inibidores Enzimáticos/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Piridinas/farmacologia , Túnica Íntima/efeitos dos fármacos , Animais , Reestenose Coronária/diagnóstico por imagem , Peptídeos e Proteínas de Sinalização Intracelular , Suínos , Ultrassonografia , Quinases Associadas a rhoRESUMO
Imidapril is an angiotensin-converting enzyme inhibitor that is widely used in treating hypertension, although the responses vary among individuals. We investigated whether a single nucleotide polymorphism at position -816 of the carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is involved in the responsiveness to imidapril medication. A total of 105 Japanese hypertensives with systolic/diastolic blood pressures (SBP/DBP) of 140/90 mmHg or higher were prescribed 5-10 mg/day of imidapril. At baseline, blood pressure levels were not different between patients with and those without the -816C allele (AA vs. AC+ CC groups). After 8 weeks of treatment, we classified the responders and non-responders based on the decline in their blood pressures, and found that the responder rate was significantly higher in the AC+CC group than in the AA group (p=0.0331). Also, the reduction in SBP was significantly greater in the AC+CC group than in the AA group (24.7+/-11.8 vs. 17.6+/-16.8 mmHg, p=0.0184). Furthermore, an in vitro reporter assay revealed that the -816C construct had significantly higher promoter activity (p<0.0001). These findings suggest that the A(-816)C polymorphism affects the transcriptional activity, and that this may account for the responsiveness to imidapril.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Carboxilesterase/genética , Hipertensão/tratamento farmacológico , Imidazolidinas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Idoso , Feminino , Genótipo , Humanos , Hipertensão/genética , Masculino , Pessoa de Meia-IdadeRESUMO
This study was conducted to determine the effects of depression and/or insomnia on masked hypertension (MHT) compared with other types of HT and on variability in home-measured blood pressure (HBP) and clinic BP (CBP). Three hundred and twenty-eight hypertensives (132 women) aged 68±10 years were classified into four BP types: controlled HT (CHT), white-coat HT, MHT and sustained HT (SHT), based on CBP (140/90 mm Hg) and morning HBP (135/85 mm Hg) measurements. A score of ⩾16 on the Center for Epidemiologic Studies Depression Scale (CES-D) was defined as depression. The mean values and s.d. of BP were calculated from measurements taken during the 14 consecutive days just before the CES-D evaluation. Compared with the CHT group, the risk of depression was 2.77-fold higher in the SHT group and even higher in the MHT group (7.02-fold). The association between depression and MHT was augmented in the presence of insomnia and was somewhat stronger in women. A HBP variability index defined as s.d./mean BPs in both morning and night time was significantly higher in MHT than in the other BP types, whereas that of CBP was not. Both morning and night-time HBP variability were significantly higher in depressive patients than in non-depressives. These suggest that depression is associated with MHT and that increases both morning and night-time HBP variability but not CBP variability. Physicians should be mindful of mental stresses such as depression in their hypertensive patients when forming strategies to control BP over the diurnal cycle.
Assuntos
Depressão/complicações , Hipertensão Mascarada/psicologia , Distúrbios do Início e da Manutenção do Sono/complicações , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Determinação da Pressão Arterial , Feminino , Humanos , Hipertensão/epidemiologia , Japão/epidemiologia , Masculino , Hipertensão Mascarada/complicações , Pessoa de Meia-Idade , Prevalência , Estudos ProspectivosRESUMO
BACKGROUND: It remains unclear how closely the small dense low-density lipoprotein (LDL) (diameter < or =25.5 nm) is associated with various types of coronary heart disease (CHD) in Japanese patients, an ethnic group with lower serum cholesterol levels and less massive obesity compared with Western populations. METHODS AND RESULTS: We measured mean LDL particle diameter by gradient gel electrophoresis in 571 patients with CHD and in 263 healthy subjects who served as control patients. Patients with CHD were classified into acute coronary syndrome (ACS), stable CHD and vasospastic angina. High-density lipoprotein cholesterol and apolipoprotein-A1 and -B were significantly different between patients with CHD and controls. LDL size in patients with CHD was markedly smaller than that in controls in both men and women (25.5 +/- 0.7 vs 25.9 +/- 0.4 and 25.7 +/- 0.7 vs 26.0 +/- 0.5 nm, respectively). LDL cholesterol was significantly higher in patients with ACS than in other groups. Plasma levels of high-density lipoprotein cholesterol decreased as the number of diseased vessels or angiographic coronary severity evaluated by Gensini score increased, but the LDL size was comparable irrespective of the type of CHD and the extent and severity of the lesions. Multiple logistic regression analysis revealed that small dense LDL was independently associated with the incidence of CHD in both sexes (odds ratio [OR] 3.5, 95% CI 2.1-5.7, and OR 2.9, 95% CI 1.5-5.6, P <.005). CONCLUSION: Our study suggests that the small dense LDL is strongly associated with various types of CHD, independent of traditional and nontraditional coronary risk factors, but is not related to the severity and extent of the coronary lesions.
Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Lipoproteínas LDL/sangue , Adulto , Angina Pectoris/sangue , Angina Pectoris/epidemiologia , Angina Instável/sangue , Angina Instável/epidemiologia , Apolipoproteína A-I/sangue , Povo Asiático , Colesterol/sangue , Feminino , Humanos , Japão , Lipoproteína(a)/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Tamanho da Partícula , Fenótipo , Fatores de Risco , Índice de Gravidade de Doença , Triglicerídeos/sangueRESUMO
BACKGROUND: Exuberant smooth muscle cells (SMCs) hyperplasia is the major cause of postangioplasty restenosis. We suggested that circulating smooth muscle progenitor cells might contribute to lesion formation after vascular injury. METHODS: We extensively investigated the cellular constituents during neointimal formation after mechanical vascular injury. RESULTS: A large wire was inserted into the mouse femoral artery, causing complete endothelial denudation and marked enlargement of the lumen with massive apoptosis of medial SMCs. At 2 h, the injured artery remained dilated with a thin media containing very few cells. A scanning electron microscopy showed fibrin and platelet deposition at the luminal side. One week after the injury, CD45-positive hematopoietic cells accumulated at the luminal side. Those CD45-positive cells gradually disappeared, whereas neointimal hyperplasia was formed with alpha-smooth muscle actin (SMA) positive cells. Bone marrow cells and peripheral mononuclear cells differentiated into alpha-SMA-positive cells in the presence of PDGF and basic FGF. Moreover, in bone marrow chimeric mice, bone-marrow-derived cells substantially contributed to neointimal hyperplasia after wire injury. CONCLUSION: These results suggest that early accumulation of hematopoietic cells may play a role in the pathogenesis of SMC hyperplasia under certain circumstances.
Assuntos
Artéria Femoral/ultraestrutura , Células-Tronco Hematopoéticas/patologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/ultraestrutura , Túnica Íntima/patologia , Actinas/genética , Actinas/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Artéria Femoral/lesões , Artéria Femoral/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Hiperplasia , Imuno-Histoquímica , Antígenos Comuns de Leucócito/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Microscopia Eletrônica de Varredura , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , RNA Mensageiro/metabolismo , Túnica Íntima/metabolismo , Túnica Íntima/fisiopatologiaRESUMO
AIM: Among the many factors related to bone marrow cell mobilization, local inflammation induced by cytokines may drive bone marrow cells to the vascular wall, resulting in a thickened neointima. However, the relationship between inflammatory reactions and bone marrow cell invasion has not yet been fully clarified. METHODS: We inserted a large wire into the femoral artery in male balb/c(WT), interleukin (IL)-6-knockout (KO) and bone marrow-transplanted (BMT) mice that had received bone marrow cells from KO mice. Immunohistochemistry was performed to evaluate the degree of intimal hyperplasia and inflammation following vascular injury. RESULTS: Three days after the vascular injury, the number of CD34/Sca-1-positive cells in the blood was higher in the KO mice. The numbers of apoptotic cells in the neointima was lower in the KO and BMT mice at two hours after injury. The morphometric analysis performed at one and four weeks after injury showed that the intima/media ratio was significantly lower in the KO and BMT mice, while CD34-positive cells were much more frequent in the WT mice. Furthermore, re-endothelialization appeared earlier in the KO and BMT mice than in the WT mice. No differences in the levels of vascular endothelial growth factor or hepatocyte growth factor were observed in the mice sera between the WT, KO and BMT mice after injury. The in vitro culture of bone marrow cells showed more differentiated smooth muscle-like cells in the WT mice than in the KO mice. CONCLUSIONS: IL-6 is involved in neointimal formation following vascular injury, possibly acting through inflammatory effects inducing the production of bone marrow cells.
Assuntos
Células da Medula Óssea/citologia , Interleucina-6/fisiologia , Neointima/metabolismo , Animais , Antígenos CD34/metabolismo , Apoptose , Células da Medula Óssea/metabolismo , Transplante de Medula Óssea , Endotélio Vascular/metabolismo , Citometria de Fluxo , Fator de Crescimento de Hepatócito/metabolismo , Inflamação/patologia , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) reduce the mortality in the chronic phase of myocardial infarction (MI), and similar effects of angiotensin receptor blockers (ARB) have been reported. However, these effects of ARB have not yet been established in Japanese patients. A multicenter randomized study was designed for the present study to examine the effect of valsartan as compared to that of ACEI against left ventricular dysfunction after MI. METHODS AND RESULTS: Patients with acute MI were randomly allocated to either the valsartan group (n=120; mean age 63 +/-1.0) or the ACEI group (n=121; mean age 62.9 +/-1.0) and followed up until 6 months. Left ventriculography was performed during hospital admission and at 6 months. The blood pressure was similar in the 2 groups throughout the study. The incidences of cardiovascular events and target vessel revascularization were similar, although that of adverse events was significantly higher in the ACEI (12.4%) than in the valsartan group (3.3%; P<0.05). There were no differences in left ventricular ejection fraction and left ventricular end-diastolic volume index between the groups. CONCLUSIONS: Valsartan exhibits similar efficacy effective to that of ACEI in preventing left ventricular dysfunction in Japanese patients with acute MI, and is, in addition, better tolerated than ACEI.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Disfunção Ventricular Esquerda/prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Povo Asiático , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/etnologia , Volume Sistólico/efeitos dos fármacos , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Valina/efeitos adversos , Valina/uso terapêutico , Valsartana , Disfunção Ventricular Esquerda/etnologia , Disfunção Ventricular Esquerda/etiologia , Remodelação Ventricular/efeitos dos fármacosRESUMO
OBJECTIVE: Recent studies have suggested that granulocyte colony-stimulating factor (G-CSF) may improve cardiac function after acute myocardial infarction (AMI) by accelerating angiogenesis or cardiomyogenesis, but negative results and side effect of G-CSF have also been reported. However, no previous studies have used large animal models of ischemia/reperfusion to investigate the effect and side effect of G-CSF after AMI. METHODS: The diagonal branch of the left anterior descending coronary artery of swine was balloon-occluded for 1 h and then reperfused. The animals of the G-CSF group were injected with G-CSF subcutaneously (5.0 microg/kg/day) for 6 days after MI and then sacrificed after 4 weeks. The control group received the same volume of saline. RESULTS: There were no differences between the groups in the rate of thrombotic obstruction or progression of stenosis lesion in coronary angiography. The ejection fraction and end-diastolic volume in the G-CSF group were not significantly improved over the control values. The fibrotic area was significantly smaller in the G-CSF group than in the controls (P<0.05), and the numbers of vessels counted in anti-von Willebrand factor and anti-alpha-smooth muscle actin-stained sections were significantly larger (P<0.005 and P<0.05, respectively). The expression of collagen III mRNA was significantly lower in the G-CSF group than in the control in the infarct (P<0.0005) and border areas (P<0.005), and TGF-beta mRNA was significantly lower in the G-CSF group in the border area (P<0.05). CONCLUSIONS: G-CSF could modify the healing process after AMI by accelerating angiogenesis in a swine ischemia/reperfusion model. At the dose administered, however, G-CSF did not seem to improve the global cardiac function.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Animais , Oclusão com Balão , Biomarcadores/sangue , Angiografia Coronária , Fibrose/prevenção & controle , Técnicas Imunoenzimáticas , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Reperfusão Miocárdica/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SuínosRESUMO
BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) affects injured arteries through early endothelialization. Some reports, however, have cautioned that the restenosis rate may increase after G-CSF injection. In the present study, high-dose G-CSF was administered to mice with vascular injury to clarify its effect. METHODS AND RESULTS: Mice were received daily subcutaneous injections of saline or a high dose (300 microg/kg) of G-CSF for 5 days after vascular injury. In the FACS analysis, CD34-/Sca-1-positive progenitor cells were more abundant in the G-CSF group (p<0.05). Neointimal hyperplasia was more evident in the G-CSF group at 1 week (p<0.05), whereas at 4 weeks it was more evident in the control group (p<0.01). TUNEL-positive cells in the arterial wall were more numerous in the G-CSF group at day 1 (p<0.01). CD34-positive cells were observed in the G-CSF group at 1 week. Re-endothelialization appeared earlier in the G-CSF group (at 4 weeks; p<0.01). An increased number of 1A4-positive smooth muscle cells were found in bone marrow cell culture treated with G-CSF. CONCLUSION: High-dose G-CSF induced neointimal proliferation through excessive inflammation and bone marrow cell mobilization in the early phase. In the late phase, however, it induced early re-endothelialization and thereby inhibited neointimal hyperplasia.
Assuntos
Artéria Femoral/lesões , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Animais , Antígenos CD34/metabolismo , Antígenos Ly/metabolismo , Proliferação de Células/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Hiperplasia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco/metabolismo , Células-Tronco/patologiaRESUMO
AIM: Recent evidence suggests that small dense low-density lipoprotein (sd-LDL) particles are more atherogenic than large-LDL in spite of their lower cholesterol content. This study aimed to determine whether sd-LDL-cholesterol (sd-LDL-C) is superior to LDL-C as a biomarker of coronary heart disease (CHD). METHODS: LDL particle size determined by gradient gel electrophoresis and sd-LDL-C concentrations quantified by heparin-magnesium precipitation were compared between 482 stable CHD patients and 389 non-diabetic subjects without CHD who were not receiving any lipid-lowering drugs. RESULTS: Both male and female CHD patients had significantly smaller LDL particles and lower large-LDL-C concentrations (estimated by subtracting the sd-LDL-C concentration from the LDL-C concentration), and significantly higher sd-LDL-C concentrations than the control subjects. LDL-C concentrations were modestly higher and sd-LDL-C concentrations were significantly higher in 258 patients with angiographically documented severe CHD than in the patients with mild CHD irrespective of treatment by LDL-lowering drugs and history of myocardial infarction and/or coronary revascularization. Large-LDL-C concentrations, in contrast, were similar between the two groups. Multivariate logistic regression analysis revealed that sd-LDL-C levels were significantly associated with severe CHD independently of LDL-C. CONCLUSION: sd-LDL-C levels are more powerful than LDL-C levels for the determination of severe stable CHD.
Assuntos
LDL-Colesterol/sangue , Doença da Artéria Coronariana/diagnóstico , Doença das Coronárias/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Doença das Coronárias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da PartículaRESUMO
BACKGROUND: Recent studies suggest that neointimal cells in atherosclerotic lesions are partly derived from bone marrow (BM) cells. However, studies with large animal models have not yet clarified how BM cells contribute to neointimal formation in restenotic lesions. We examined the expression of CD34, a hematopoietic stem cell marker, in the neointima after coronary stent implantation in porcine. METHODS: Pigs underwent balloon injury in the coronary arteries followed by stent implantation. The arteries were harvested at 3, 7, and 28 days after the stenting. The samples were used for immunohistochemistry for CD34, smooth muscle embryo (SMemb), alpha-smooth muscle cell actin (alpha-SMA), macrophage, c-kit, and AC133 antibodies. In morphometric analysis, each layer of vascular wall was calculated in the sections. RESULTS: At 3 days, the expressions of CD34 and SMemb were minimal, and many macrophages were seen around the stent struts. At 7 days, co-expression of CD34 and SMemb was observed around the struts, and 11.5% of the neointimal cells were stained by CD34. In addition, c-kit positive cells and AC133 positive cells are detected in neointimal area. At 28 days, the neointima had thickened and expressed alpha-SMA rather than SMemb, and a few CD34-positive cells were detected. In morphometric analysis, luminal area/total vascular area was significantly smaller and intimal area/total vascular area was significantly bigger in 7 and 28 days than in the day of implantation. CONCLUSION: BM cells of possibly hematopoietic origin partially contributed to neointimal formation after coronary stent implantation in a large animal model.
Assuntos
Antígenos CD34/metabolismo , Células da Medula Óssea/fisiologia , Stents , Túnica Íntima/patologia , Antígeno AC133 , Actinas/imunologia , Actinas/metabolismo , Animais , Anticorpos/metabolismo , Antígenos CD/imunologia , Biomarcadores/metabolismo , Células Cultivadas , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Glicoproteínas/imunologia , Imuno-Histoquímica , Macrófagos/patologia , Masculino , Modelos Animais , Cadeias Pesadas de Miosina/imunologia , Cadeias Pesadas de Miosina/metabolismo , Miosina não Muscular Tipo IIB/imunologia , Miosina não Muscular Tipo IIB/metabolismo , Peptídeos/imunologia , Suínos , Fatores de TempoRESUMO
BACKGROUND: Tumor necrosis factor (TNF)-alpha is linked to the pathogenesis of cardiovascular diseases, but how it affects myocardial infarction (MI), so the present study examined the effects of TNF-alpha and the involvement of intercellular adhesion molecule (ICAM)-1 on MI. METHODS AND RESULTS: Left coronary arteries of C57BL/6 wild type (WT) and TNF-alpha knockout (KO) mice were ligated and the mice were killed 1, 3, and 7 days later. Fractional shortening on echocardiography of the KO mice was significantly higher than that of the WT mice from day 1 to 7 (p<0.01). The ICAM-1 mRNA in the infarcted area of the KO mice was significantly lower than that of the WT from day 1 (p<0.01) to 7. In immunohistochemistry, the expression of ICAM-1 was weaker in the KO than in the WT mice. The number of neutrophils in the KO mice peaked at day 1, but even this peak level failed to reach the levels in the infarcted (p<0.01) and peri-infarcted areas (p<0.05) in the WT. The number of macrophages in the KO mice peaked at day 7, but this peak level failed to reach the levels in the infarcted (p<0.01) and peri-infarcted areas (p<0.05) in the WT. CONCLUSION: In a permanent occlusion model of MI TNF-alpha decreased cardiac function and ameliorated myocardial remodeling through the induction of ICAM-1.