RESUMO
Metabolic syndrome (Mets) is the major contributor to the onset of metabolic complications, such as hypertension, type 2 diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease, resulting in cardiovascular diseases. C57BL/6 mice on a high-fat and high-sucrose diet (HFHSD) are a well-established model of Mets but have minor endothelial dysfunction in isolated aortas without perivascular adipose tissue (PVAT). The purpose of this study was to evaluate the effects of additional factors such as DM, dyslipidemia, and steatohepatitis on endothelial dysfunction in aortas without PVAT. Here, we employed eight-week-old male C57BL/6 mice fed with a normal diet (ND), HFHSD, steatohepatitis choline-deficient HFHSD (HFHSD-SH), and HFHSD containing 1% cholesterol and 0.1% deoxycholic acid (HFHSD-Chol) for 16 weeks. At week 20, some HFHSD-fed mice were treated with streptozocin to develop diabetes (HFHSD-DM). In PVAT-free aortas, the endothelial-dependent relaxation (EDR) did not differ between ND and HFHSD (p = 0.25), but in aortas with PVAT, the EDR of HFHSD-fed mice was impaired compared with ND-fed mice (p = 0.005). HFHSD-DM, HFHSD-SH, and HFHSD-Chol impaired the EDR in aortas without PVAT (p < 0.001, p = 0.019, and p = 0.009 vs. ND, respectively). Furthermore, tempol rescued the EDR in those models. In the Mets model, the EDR is compromised by PVAT, but with the addition of DM, dyslipidemia, and SH, the vessels themselves may result in impaired EDR.
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Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Síndrome Metabólica , Doenças Vasculares , Masculino , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Sacarose/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Camundongos Endogâmicos C57BL , Tecido Adiposo/metabolismo , Aorta/metabolismo , Dieta Hiperlipídica/efeitos adversos , Doenças Vasculares/metabolismo , Síndrome Metabólica/metabolismo , Fígado Gorduroso/metabolismoRESUMO
BACKGROUND: There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.MethodsâandâResults:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for ≥30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin. CONCLUSIONS: Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.
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Fibrilação Atrial , Taquicardia Supraventricular , Animais , Fibrilação Atrial/etiologia , Estimulação Cardíaca Artificial/efeitos adversos , Modelos Animais de Doenças , Átrios do Coração , Humanos , CamundongosRESUMO
BACKGROUND: Artificial oxygen carriers (HbV) can treat hemorrhagic shock with lethal arrhythmias (VT/VF). No reports exist on subacute HbV's effects. METHODS: Acute and subacute resuscitation effects with anti-arrhythmogenesis of HbV were studied in 85% blood exchange rat model (85%-Model). Lethal 85%-Model was created by bone marrow transfusion and femoral artery bleeding in 80 SD rats in HbV-administered group (HbV-group), washed erythrocyte-administered group (wRBC-group), and 5% albumin-administered group (ALB-group). Survival rates, anti-arrhythmic efficacy by optical mapping system (OMP) with electrophysiological study (EPS) in Langendorff heart, cardiac autonomic activity by heart rate variability (HRV) and ventricular arrhythmias by 24-h electrocardiogram telemetry monitoring (24 h-ECG) in awake, and left ventricular function by echocardiography (left ventricular ejection fraction [LVEF]) were measured. RESULTS: All rats in HbV- and wRBC-groups survived for 4 weeks, whereas no rats in ALB-group. HbV and wRBC acutely suppressed VT/VF in Langendorff heart through ameliorating action potential duration dispersion (APDd) analyzed by OMP with EPS. For subacute analysis, 50% blood exchange by 5% albumin was used (ALB-group 50). Subacute salutary effect on APDd and VT/VF inducibility was confirmed in HbV- and wRBC-groups. 24 h-ECG showed that HbV and wRBC suppressed none-sustained ventricular tachycardia (NSVT) and sympathetic component of HRV (LF/HF) with preserved LVEF (HbV-group, wRBC-group vs. ALB-group 50; NSVT numbers/days, 0.5 ± 0.3, 0.4 ± 0.3 vs. 3.9 ± 1.2*; LF/HF, 1.1 ± 0.2, 0.8 ± 0.2 vs. 3.5 ± 1.0*; LVEF, 84 ± 5, 83 ± 4, vs. 77 ± 4%*; *p < 0.05). CONCLUSIONS: Collectively, HbV has sustained antiarrhythmic effect in subacute 85%-Model by ameliorating electrical remodeling and improving arrhythmogenic modifying factors (HRV and LVEF). These findings are useful in now continuing clinical trials of HbV.
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Anemia , Taquicardia Ventricular , Albuminas/uso terapêutico , Anemia/tratamento farmacológico , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Hemodiluição , Hemoglobinas , Infusões Intraósseas , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Long term field observations have revealed that the inhibition of transpiration by heavy rainfall promotes immediate positive shift in the trans-root electric potential (TRP), indicating activation of the xylem proton pump in the tree root system presumably participating in acropetal water transport. This phenomenon is indicative of signal transmission from the aerial part to the root system via change in the xylem hydraulic pressure. To test this hypothesis, we constructed a new device that enables the simultaneous recording of artificially applied xylem hydraulic pressure and the change in the TRP of tree saplings. With the application of artificial pressure to the xylem vessels (20-62 kPa), TRP shifted towards positive potential by 20-80 mV, which indicates the activation of the proton pump in the root xylem. The reaction was observed in 11 tree species, six deciduous and five evergreen, although only during the resting phase of the xylem proton pump (May to October) when the transpiration rates were high. Contrastingly the application of tension (negative pressure) produced no reaction. Simultaneous determination of the two components of the TRP, i.e. Vps (electric membrane potential difference across root surface cell membrane) and Vpx (electric membrane potential difference between root symplast and xylem vessel), are performed using the intra-cellular micro-electrode technique throughout the four seasons. Application of excess xylem hydraulic pressure had no significant effect on Vps, while it brought about hyper-polarisation of Vpx except during the winter season, most significantly during summer when transpiration is vigorous and the xylem pump is in a resting state. Such effect of excess xylem pressure was, however, not observed under anoxia.
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Raízes de Plantas , Bombas de Próton , Xilema , Folhas de Planta/fisiologia , Raízes de Plantas/metabolismo , Transpiração Vegetal/fisiologia , Água/metabolismo , Xilema/fisiologiaRESUMO
Arterial stiffness is an age-related disorder. In the medial layer of arteries, mechanical fracture due to fatigue failure for the pulsatile wall strain causes medial degeneration vascular remodeling. The alteration of extracellular matrix composition and arterial geometry result in structural arterial stiffness. Calcium deposition and other factors such as advanced glycation end product-mediated collagen cross-linking aggravate the structural arterial stiffness. On the other hand, endothelial dysfunction is a cause of arterial stiffness. The biological molecular mechanisms relating to aging are known to involve the progression of arterial stiffness. Arterial stiffness further applies stress on large arteries and also microcirculation. Therefore, it is closely related to adverse outcomes in cardiovascular and cerebrovascular system. Cardio-ankle vascular index (CAVI) is a promising diagnostic tool for evaluating arterial stiffness. The principle is based on stiffness parameter ß, which is an index intended to assess the distensibility of carotid artery. Stiffness parameter ß is a two-dimensional technique obtained from changes of arterial diameter by pulse in one section. CAVI applied the stiffness parameter ß to all of the arterial segments between heart and ankle using pulse wave velocity. CAVI has been commercially available for a decade and the clinical data of its effectiveness has accumulated. The characteristics of CAVI differ from other physiological tests of arterial stiffness due to the independency from blood pressure at the time of examination. This review describes the pathophysiology of arterial stiffness and CAVI. Molecular mechanisms will also be covered.
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Artérias/fisiologia , Índice Vascular Coração-Tornozelo , Rigidez Vascular , Algoritmos , Artérias/fisiopatologia , Biomarcadores , Índice Vascular Coração-Tornozelo/métodos , Índice Vascular Coração-Tornozelo/normas , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares , Feminino , Humanos , Masculino , Modelos Cardiovasculares , PrognósticoRESUMO
BACKGROUND: To obtain a saphenous vein graft (SVG) for coronary artery bypass grafting (CABG), the benefit of using a no-touch (NT) technique in vascular function has not been fully investigated. MethodsâandâResults: The pathological and physiological functions of human SVGs with a NT technique to preserve the perivascular adipose tissue (PVAT) and ones obtained by using a conventional (CON) technique removing PVAT, were examined. Immunohistochemistry of the section of SVGs showed that the phosphorylation of endothelial nitric oxide synthase in the endothelium of the NT group was more responsive to vascular endothelial growth factor. A myograph of SVGs showed greater contraction with phenylephrine in the NT group. However, the strong contraction was eliminated in SVGs taken by electrocautery. In the 10 patients whose SVGs were taken without electrocautery, endothelial-dependent relaxation with bradykinin was apparently increased in the CON group more than in the NT group. Smooth muscle relaxation with nitroprusside was higher in the CON group at the lower concentrations; however, the relaxation became greater in the NT group at the high concentrations. Therefore, the effect of neutralizing PVAT-released factors in the both groups was further examined. After medium of NT and CON were exchanged in half, relaxation of SVGs was immediately restored in the NT group. CONCLUSIONS: The results suggest that the NT technique preserves the functions of vasoconstriction and relaxation. Also, the presence of PVAT-released vasoconstrictive factors was suspected.
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Ponte de Artéria Coronária , Veia Safena/fisiopatologia , Transplantes/fisiopatologia , Vasoconstrição , Vasodilatação , Idoso , Idoso de 80 Anos ou mais , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Óxido Nítrico/metabolismo , Veia Safena/metabolismo , Veia Safena/patologia , Transplantes/metabolismo , Transplantes/patologiaRESUMO
Purulent pericarditis is a rare disease in the antibiotic era. The common pathogens of purulent pericarditis are gram-positive species such as Staphylococcus aureus. Streptococcus pneumoniae, Salmonella, Haemophilus, fungal pathogens/tuberculosis can also result in purulent pericarditis. We report an old male case of purulent pericarditis by Escherichia coli. He came to our hospital suffering from leg edema for 3 months. Echocardiography revealed the large amount of pericardial effusion, and he was admitted to test the cause of pericardial effusion without high fever, tachycardia, and shock vital signs. On the third day, he suddenly presented vital shock. We performed emergency cardiopulmonary resuscitation and pericardiocentesis. Appearance of pericardial effusion was hemorrhagic and purulent. The gram stain revealed remarkable E. coli invasion to pericardial space. Antibiotic therapy was immediately started; however, he died on sixth day with septic shock. The cytological examination of pericardial effusion suggested the invasion of malignant lymphoma to pericardium. This case showed subacute or chronic process of pericarditis without severe clinical and laboratory sings before admission. Nevertheless, bacterial purulent pericarditis usually shows acute clinical manifestation; the first process of this case was very silent. Immunosuppression of malignant lymphoma might make E. coli translocation from gastrointestinal tract to pericardial space, and bacterial pericarditis was progressed to purulent pericarditis. In the latter process, this case showed unexpected rush progression to death by sepsis from purulent pericarditis. Immediate pericardiocentesis should be performed for a prompt diagnosis of purulent pericarditis, and it might have improved the outcome of this case.
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Infecções por Escherichia coli/complicações , Linfoma/complicações , Derrame Pericárdico/etiologia , Pericardite/etiologia , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Reanimação Cardiopulmonar/métodos , Progressão da Doença , Ecocardiografia , Eletrocardiografia , Escherichia coli/isolamento & purificação , Evolução Fatal , Humanos , Masculino , Derrame Pericárdico/microbiologia , Derrame Pericárdico/terapia , Pericardiocentese/métodos , Pericardite/microbiologia , Pericardite/terapia , Pericárdio/patologia , Choque Séptico/etiologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. APPROACH AND RESULTS: We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. CONCLUSIONS: Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus.
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Artéria Braquial/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Células Endoteliais/enzimologia , Endotélio Vascular/enzimologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Vasodilatação , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Adulto , Idoso , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiopatologia , Estudos de Casos e Controles , Células Cultivadas , Diabetes Mellitus Tipo 2/fisiopatologia , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Ativação Enzimática , Feminino , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/farmacologia , Vasodilatação/efeitos dos fármacos , Proteínas Wnt/antagonistas & inibidores , Proteínas Wnt/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Proteína Wnt-5aRESUMO
There have been very few studies on serum biomarkers associated with hypertension in disaster situations. We assessed biomarkers associated with disaster-related hypertension (DRH) due to the Great East Japan Earthquake of March 2011.We collected blood samples from members of the Japan Self Defense Forces (JSDF) (n = 77) after completing disaster relief operations. We divided them into two groups based on systolic blood pressure. We defined DRH as either systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg at the time of completing missions.In subjects with DRH, the mean blood pressure was 143.5 ± 5.0/99.5 ± 2.4 mmHg. Height and body weight measurements were slightly greater in the DRH group but the differences were not significant, and age was significantly higher in the DRH group. There were no differences in serum biochemical tests including metabolic markers, sulfur-containing amino acids, and cytokines. Among nitric oxide-related amino acids, asymmetric dimethylarginine (ADMA) was lower in the DRH group than in the normotension group (0.40 ± 0.02 versus 0.31 ± 0.02 µmol/L P = 0.04). The serum oxidative stress metabolite levels (d-ROMs; indicators of active oxygen metabolite products) were significantly higher in the DRH group (273.6 ± 6.08 versus 313.5 ± 13.7 U.CARR P = 0.016). Using multivariable regression analysis, d-ROMs levels were particularly predictive for DRH.Oxidative stress is associated with DRH in responders to the disaster of the Great East Japan Earthquake.
Assuntos
Pressão Sanguínea/fisiologia , Terremotos , Hipertensão/sangue , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Adulto , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hipertensão/fisiopatologia , Japão , MasculinoRESUMO
Left ventricular (LV) diastolic dysfunction is considered the main cause of heart failure with preserved ejection fraction (HFpEF). There have been few reports on the correlation between LV diastolic dysfunction and arterial stiffness in patients with clinical cardiovascular disease.This cross-sectional study enrolled 100 patients (67 men, 33 women; mean age, 70 years). All participants were diagnosed with cardiovascular disease. A total of 89 (89%) patients had coronary artery disease or HF. Patients with reduced EF and valvular disease were excluded. Arterial stiffness was assessed by the cardio-ankle vascular index (CAVI), and LV diastolic dysfunction was estimated using echocardiography. The patients were divided into two groups based on the median value of CAVI. In all patients the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') was significantly higher in the high CAVI group than in the low CAVI group (15.5 ± 6.4 versus 12.5 ± 2.9, P = 0.003). In the HF subgroup, E/e' was also significantly higher in the high CAVI group than in the low CAVI group (17.2 ± 5.9 versus 13.0 ± 3.1, P = 0.026). In univariate regression analysis, CAVI was significantly associated with E/e' in all patients (ß = 0.28, P = 0.004) and in HF patients (ß = 0.4, P = 0.028). Also in multivariate analysis, CAVI remained as an independent predictive factor of E/e' (ß = 0.252, P = 0.037).A high CAVI was independently associated with LV diastolic dysfunction in patients with clinical cardiovascular disease. These results suggested that arterial stiffness contributed to the development of LV diastolic dysfunction.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Rigidez Vascular/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Artérias , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos Transversais , Diástole , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnósticoRESUMO
Biological sex is one of the major factors characterizing the heart failure (HF) patient phenotype. Understanding sex-related differences in HF is crucial to implement personalized care for HF patients with various phenotypes. There are sex differences in left ventricular (LV) remodeling patterns in the HF setting, namely, more likely concentric remodeling and diastolic dysfunction in women and eccentric remodeling and systolic dysfunction in men. Recently supra-normal EF (snLVEF) has been recognized as a risk of worse outcome. This pathology might be more relevant in female patients. The possible mechanism may be through coronary microvascular dysfunction and sympathetic nerve overactivation from the findings of previous studies. Further, estrogen deficit might play a significant role in this pathophysiology. The sex difference in body composition may also be related to the difference in LV remodeling and outcome. Lower implementation in guideline-directed medical therapy (GDMT) in female HFrEF patients might also be one of the factors related to sex differences in relation to outcomes. In this review, we will discuss the sex differences in cardiac and clinical phenotypes and their relation to outcomes in HF patients and further discuss how to provide appropriate treatment strategies for female patients.
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Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) show cardiovascular protective effects, regardless of the patient's history of diabetes mellitus (DM). SGLT2is suppressed cardiovascular adverse events in patients with type 2 DM, and furthermore, SGLT-2is reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF. Along with these research findings, SGLT-2is are recommended for patients with HF in the latest guidelines. Despite these benefits, the concern surrounding the increasing risk of body weight loss and other adverse events has not yet been resolved, especially for patients with sarcopenia or frailty. The DAPA-HF and DELIVER trials consistently showed the efficacy and safety of SGLT-2i for HF patients with frailty. However, the Rockwood frailty index that derived from a cumulative deficit model was employed for frailty assessment in these trials, which might not be suitable for the evaluation of physical frailty or sarcopenia alone. There is no fixed consensus on which evaluation tool to use or its cutoff value for the diagnosis and assessment of frailty in HF patients, or which patients can receive SGLT-2i safely. In this review, we summarize the methodology of frailty assessment and discuss the efficacy and safety of SGLT-2i for HF patients with sarcopenia or frailty.
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Coronary microcirculation has multiple layers of autoregulatory function to maintain resting flow and augment hyperemic flow in response to myocardial demands. Functional or structural alterations in the coronary microvascular function are frequently observed in patients with heart failure with preserved or reduced ejection fraction, which may lead to myocardial ischemic injury and resultant worsening of clinical outcomes. In this review, we describe our current understanding of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved and reduced ejection fraction.
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Venous thromboembolism (VTE) is a common comorbidity of cancer, often referred to as cancer-associated thrombosis (CAT). Even though its prevalence has been increasing, its clinical picture has not been thoroughly investigated. In this single-center retrospective observational study, 259 patients who were treated for pulmonary embolism (PE) between January 2015 and December 2020 were available for analysis. The patients were divided by the presence or absence of concomitant malignancy, and those with malignancy (N = 120, 46%) were further classified into active (N = 40, 15%) and inactive groups according to the treatment status of malignancy. In patients with malignancy, PE was more often diagnosed incidentally by computed tomography or D-dimer testing, and the proportion of massive PE was lower. Although D-dimer levels overall decreased after the initiation of anticoagulation therapy, concomitant malignancy was independently associated with higher D-dimer at discharge despite the lower severity of PE at onset. The patients with malignancy had a poor prognosis during post-discharge follow-up. Active malignancy was independently associated with major adverse cardiovascular events (MACE) and major bleeding. D-dimer at discharge was an independent predictor of mortality even after adjustment for malignancy. This study's findings suggest that CAT-PE patients might have hypercoagulable states, which can potentially lead to a poorer prognosis.
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AIMS: The long-term prognostic value of the bioavailability of L-arginine, an important source of nitric oxide for the maintenance of vascular endothelial function, has not been investigated fully. We therefore investigated the relationship between amino acid profile and long-term prognosis in patients with a history of standby coronary angiography. METHODS: We measured the serum concentrations of L-arginine, L-citrulline, and L-ornithine by high-speed liquid chromatography. We examined the relationship between the L-arginine/L-ornithine ratio and the incidence of all-cause death, cardiovascular death, and major adverse cardiovascular events (MACEs) in 262 patients (202 men and 60 women, age 65±13 years) who underwent coronary angiography over a period of ≤ 10 years. RESULTS: During the observation period of 5.5±3.2 years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, while 32 (12%) had MACEs. Cox regression analysis revealed that L-arginine/L-ornithine ratio was associated with an increased risk for all-cause death (unadjusted hazard ratio, 95% confidence interval) (0.940, 0.888-0.995) and cardiovascular death (0.895, 0.821-0.965) (pï¼0.05 for all). In a model adjusted for age, sex, hypertension, hyperlipidemia, diabetes, current smoking, renal function, and log10-transformed brain natriuretic peptide level, cardiovascular death (0.911, 0.839-0.990, p=0.028) retained an association with a low L-arginine/ L-ornithine ratio. When the patients were grouped according to an L-arginine/L-ornithine ratio of 1.16, the lower L-arginine/L-ornithine ratio group had significantly higher incidence of all-cause death, cardiovascular death, and MACEs. CONCLUSION: A low L-arginine/L-ornithine ratio may be associated with increased 10-year cardiac mortality.
Assuntos
Arginina , Hipertensão , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Citrulina , Prognóstico , Ornitina/metabolismoRESUMO
A wide range of anti-myocardial autoantibodies have been reported since the 1970s. Among them, autoantibodies against the ß1-adrenergic receptor (ß1AR-AAb) have been the most thoroughly investigated, especially in dilated cardiomyopathy (DCM). Β1AR-Aabs have agonist effects inducing desensitization of ß1AR, cardiomyocyte apoptosis, and sustained calcium influx which lead to cardiac dysfunction and arrhythmias. Β1AR-Aab has been reported to be detected in approximately 40% of patients with DCM, and the presence of the antibody has been associated with worse clinical outcomes. The removal of anti-myocardial autoantibodies including ß1AR-AAb by immunoadsorption is beneficial for the improvement of cardiac function for DCM patients. However, several studies have suggested that its efficacy depended on the removal of AAbs belonging to the IgG3 subclass, not total IgG. IgG subclasses differ in the structure of the Fc region, suggesting that the mechanism of action of ß1AR-AAb differs depending on the IgG subclasses. Our previous clinical research demonstrated that the patients with ß1AR-AAb better responded to ß-blocker therapy, but the following studies found that its response also differed among IgG subclasses. Further studies are needed to elucidate the possible pathogenic role of IgG subclasses of ß1AR-AAbs in DCM, and the broad spectrum of cardiovascular diseases including HF with preserved ejection fraction.
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Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia.
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Diabetes Mellitus Tipo 2 , Hiperemia , Masculino , Humanos , Feminino , Artéria Braquial , Diabetes Mellitus Tipo 2/complicações , Reprodutibilidade dos Testes , AntebraçoRESUMO
ST-segment elevation myocardial infarction (STEMI) can be caused by coronary artery vasospasm (VSA) due to endothelial dysfunction. However, the clinical role of endothelial function tests in VSA-induced STEMI is not fully understood. We present the case of a 43-year-old woman with atypical chest pain and no coronary risk factors. STEMI caused by VSA was diagnosed. Flow-mediated vasodilatation (FMD) and EndPAT tests were performed; the FMD and reactive hyperaemia index were 3.8% and 1.23, respectively. Endothelial dysfunction is the putative cause of STEMI. FMD and EndPAT tests might be useful for predicting adverse outcomes in young premenopausal women with VSA.