A single dose of angiotensin-(1-7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge.

OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.

Arterial stiffness indices, pulse wave velocity and central systolic blood pressure, are able to discriminate between obese and non-obese children.

The objectives of this study were to verify, first, if arterial stiffness indices can discriminate between obese and healthy children. Second, to evaluate arterial stiffness index predictors and hemodynamic parameters in obese children. Arterial stiffness indices evaluated were pulse wave velocity (PWV), central systolic blood pressure (SBPc), and central pulse pressure (PPc). A cross-sectional, descriptive, comparative study design was used. The sample consisted of 78 normal-weight children (8.1 ± 1.96 years) and 58 obese children (9.0 ± 1.87 years). PWV, PPc, and SBPc were significantly higher in the group of obese children than in the control group. The ROC curve analysis showed that maximum PWV and SBPc sensitivity and specificity in differentiating obese from non-obese children occurred at 4.09 m/s and 86.17 mmHg, respectively. PPc did not exhibit a discriminatory capacity between the two groups. Peripheral systolic blood pressure (SBPp), peripheral pulse pressure (PPp), and PPc (R2 = 0.98) were predictors of increased PWV. Augmentation pressure, PPp, and reflection coefficient (R2 = 0.873) were predictors of PPc. Age, augmentation index, total vascular resistance, cardiac index, and mean fat percentage (R2 = 0.801) were predictors of SBPc. CONCLUSION: This study shows for the first time that PWV > 4.09 m/s and SBPc > 86.17 mmHg are cut-off points associated with a higher risk of obesity. These results indicate that the simple, rapid, and noninvasive measurement of arterial stiffness adds prognostic information regarding cardiovascular risk, in addition to increased body mass index. WHAT IS KNOWN: • Overweight and obesity are strongly associated with comorbidities que contribute to the development of cardiovascular diseases. WHAT IS NEW: • This is the first study to show that PWV and SBPc can discriminate obese from non-obese children. These results show that, in addition to an increased BMI, a simple, rapid, and noninvasive measurement of arterial stiffness adds prognostic information on cardiovascular risk.

Advanced Levels of Chronic Venous Insufficiency are Related to an Increased in Arterial Stiffness.

BACKGROUND: Chronic venous insufficiency (CVI) is characterized by progressive inflammatory changes. Inflammatory damage occurs in the veins, adjacent tissues, and can lead to structural changes in the arteries. The aim of this study is to analyze whether the degree of CVI is associated with arterial stiffness. METHODS: Cross-sectional study including patients with CVI classified by clinical, etiological, anatomical, and pathophysiological classification (CEAP) 1 to 6. We performed correlation between the degree of CVI, central and peripheral arterial pressure, and arterial stiffness measured by brachial artery oscillometry. RESULTS: We evaluated 70 patients, 53 of whom were women with a mean age of 54.7 years. Patients with advanced degrees of venous insufficiency CEAP 4,5,6, had higher levels of systolic, diastolic, central, and peripheral arterial pressures compared to those with early stages (CEAP 1,2,3). The CEAP 4,5,6 group had higher arterial stiffness indices than the CEAP 1,2,3 group: pulse wave velocity (PWV) 9.3 m/s vs. 7.0 m/s, P < 0.001; augmentation pressure (AP) 8.0 mm Hg vs. 6.3 mm Hg; P = 0.04. There was a positive correlation between the degree of venous insufficiency measured by the venous clinical severity score, villalta score and CEAP classification, and the arterial stiffness indices (Spearman's coefficient = 0.62 for PWV and CEAP, P < 0.01). The factors influencing PWV were age, peripheral systolic arterial pressure (SAPp), and AP. CONCLUSIONS: There is a correlation between the degree of venous disease and arterial structural changes characterized by arterial pressure and stiffness indices. Degenerative changes secondary to venous insufficiency are associated with impairment of the arterial system, which has implications for the development of cardiovascular disease.

Arterial stiffness predicts amputation and death in patients with chronic limb-threatening ischemia.

OBJECTIVE: Arterial stiffness indices predict cardiovascular outcomes in patients with coronary or kidney disease; however, there is little data on the prognostic value of arterial stiffness in patients with advanced peripheral arterial disease. We determined whether arterial stiffness indices predict the outcomes of major amputation or death in patients with chronic limb-threatening ischemia (CLTI). METHODS: Arterial stiffness was prospectively measured using brachial oscillometry in patients with CLTI. After measuring arterial stiffness, patients were followed in 6-month intervals for up to 3 years and evaluated for limb preservation, occurrence of major amputation, or death. Hemodynamic variables and arterial stiffness indices were used to define predictors of amputation or death. RESULTS: A total of 136 patients presented with CLTI, and 134 (99%) of these patients required limb revascularization. At the end of follow-up (mean, 14 months), 24 patients (18%) were alive with a major amputation, and mortality was 7% (9 patients); 33 patients (24%) progressed to the combined outcome of major amputation or death. Patients having amputation and/or death (n = 33; 24%) initially presented with elevated pulse wave velocity (PWV) (13.41 ± 1.21 m/s vs 11.54 ± 1.65 m/s; P < .001), elevated augmentation index corrected to 75 beats per minute (40.42 ± 6.65% vs 27.12 ± 9.19%; P < .001), and high augmentation pressure (AP) (29.98 ± 4.32 mm Hg vs 13.40 ± 7.05 mm Hg; P < .001) compared with patients with preserved limbs. The initial ankle-brachial index (ABI) was lower in patients having amputation and/or death (0.43 ± 0.94 vs 0.62 ± 0.12; P < .001). Multivariable analysis identified PWV (odds ratio [OR], 2.62; P = .013), AP (OR, 1.56; P < .001), and ABI (OR, 0.01; P < .001) as predictors of amputation or death. ROC analysis identified patients with PWV ≤12.7 m/s (hazard ratio, 4.71; P < .001), AP ≤22.15 mm Hg (hazard ratio, 13.03; P < .001), or ABI >0.52 with an increased rate of limb preservation. CONCLUSIONS: PWV and AP, measurements of arterial stiffness, as well as the ABI, predict amputation or death in patients with CLTI.

Association Between Critical Limb Ischemia, the Society for Vascular Surgery Wound, Ischemia and Foot Infection (WIfI) Classification System and Arterial Stiffness.

BACKGROUND: Arterial stiffness analysis has been done to classify cardiovascular risk. The aim of this article is to analyze whether the group of patients with chronic limb-threatening ischemia (CLTI) has higher arterial stiffness indices than controls. The secondary objectives are to assess whether patients with advanced stages of Wound, Ischemia, and foot Infection (WIfI) classification have high levels of arterial stiffness, through multiple linear regressions to analyze whether the ankle-brachial index (ABI) and other variables are predictive of arterial stiffness. METHODS: We conducted a cross-sectional study with 66 patients with CLTI and 66 age- and sex-matched controls using brachial artery oscillometry. Hemodynamic and arterial stiffness measurements, clinical characteristics, laboratory data, and stages of WIfI classification were compared between the groups CLTI and controls. Through multiple linear regression, we identified predictors of pulse wave velocity (PWV) and augmentation index normalized to 75 beats/min (AIx@75). RESULTS: Patients with CLTI had PWV (11.8 ± 1.6 m/sec vs. 10.0 ± 1.8 m/sec, P < 0.01) and AIx@75 (29.2 ± 9.8% vs.18. ± 10.35%, P < 0.01) higher than controls. In the multiple regression model, there was influence of age (ß = 0.17, P < 0.01), antiplatelet therapy (ß = -0.15, P = 0.04), peripheral systolic pressure (ß = 0.03, P < 0.01), and clustered WIfI stages 3 and 4 (ß = 0.17, P = 0.02) of benefit of revascularization on PWV. Multiple regression analysis identified diabetes (ß = 7.51, P < 0.01) and the degree of ischemia measured by ABI (ß = -23.89, P < 0.01) as predictors of elevated AIx@75. WIfI stages 3 and 4 of estimate risk of amputation at 1 year predicts a high AIx@75 (ß = 9.77, P < 0.001) compared with stages 1 and 2. CONCLUSIONS: The degree of ischemia in CLTI patients determined by the ABI is associated with elevated arterial stiffness as measured by the AIx@75. Advanced WIfI stages were predictors of elevated PWV and AIx@75.

Changes in aortic pulse wave components, pulse pressure amplification, and hemodynamic parameters of children and adolescents with type 1 diabetes.

BACKGROUND/OBJECTIVE: Type 1 diabetes mellitus (DM1) presents important risk factors for cardiovascular events. OBJECTIVE: To compare the components of the aortic pulse wave (APW) and the hemodynamic parameters among children and adolescents with DM1 and healthy individuals. METHODS: This is a cross-sectional study, with 36 children and adolescents diagnosed with DM1 (11.9 ± 3.2 years) matched by sex and age with the control group (n = 36, 12.4 ± 2.9 years). The components of the APW and the hemodynamic parameters were evaluated non-invasively, using Mobil-O-Graph. RESULTS: On the week of the evaluation, DM1 patients presented glycated hemoglobin (hemoglobin A1C [HbA1c]) of 9.48 ± 2.22% and fasting glycemia of 222.58 ± 93.22 mg/dL. Augmentation index (AIx@75), reflection coefficient, and augmentation pressure (AP) were significantly higher in the DM1 group (29.0 ± 9.7%, 63.0 ± 7.9, and 7.8 ± 2.7 mm Hg, respectively) compared with the control group (20.6 ± 7.9%, 53.4 ± 9.1 and 4.9 ± 2.1 mm Hg, respectively). The systolic volume (52.6 ± 11.9 and 60 ± 12.4 mL) and the cardiac output (4.3 ± 0.5 and 4.6 ± 0.5 L/min) decreased in the DM1 group in relation to the control group. The pulse pressure amplification (PPA) was significantly lower in the DM1 group (1.4 ± 0.15) compared with the control group (1.6 ± 0.17). PPA correlated negatively with total vascular resistance (TVR), AP and reflection coefficient, and positively with cardiac index in both groups. In the DMI group, the AIx@75 correlated negatively with age, height, systolic volume, and PPA, and correlated positively with the TVR and reflection coefficient. CONCLUSIONS: These results confirm the presence of arterial stiffness in this population and extend the knowledge, showing, for the first time, the reduction of PPA in the DM1 group.

Applications of arterial stiffness markers in peripheral arterial disease.

Arterial stiffness has been analyzed in many different population groups with the objective of identifying cardiovascular risk early and performing specific therapeutic interventions. Increased arterial stiffness affects the capacity of the aorta and elastic arteries to adapt to pressure variations during the cardiac cycle. The main markers of arterial stiffness are pulse wave velocity (PWV), augmentation index (AIx) and central aortic pressure. They can be measured noninvasively. Patients with coronary disease or on hemodialysis who have elevated PWV or AIx have increased mortality. The association with peripheral arterial disease has been studied little. The objective of this review is to demonstrate the applicability and utility of assessing measures of arterial stiffness in patients with peripheral arterial disease.

Association between critical limb ischemia and arterial stiffness measured by brachial artery oscillometry.

BACKGROUND: Elevated arterial stiffness is associated with increased cardiovascular mortality. The relationship between arterial stiffness and critical limb ischemia (CLI) is not well established. OBJECTIVES: The objective of this study is to analyze the relationship between arterial stiffness indices and the degree of limb ischemia measured by the ankle-brachial index (ABI). METHODS: A cross-sectional study comparing patients with CLI and controls. Arterial stiffness was measured using brachial artery oscillometry. The arterial stiffness indices pulse wave velocity (PWV) and augmentation index normalized to 75 beats/min (AIx@75) were determined. Multiple linear regression was applied to identify predictors of arterial stiffness indices. RESULTS: Patients in the CLI group had higher PWV (12.1±1.9 m/s vs. 10.1±1.9 m/s, p < 0.01) and AIx@75 (31.8±7.8% vs. 17.5±10.8%, p < 0.01) than controls. Central systolic pressure was higher in the CLI group (129.2±18.4 mmHg vs. 115.2±13.1 mmHg, p < 0.01). There was an inverse relationship between AIx@75 and ABI (Pearson coefficient = 0.24, p = 0.048), but there was no relationship between ABI and PWV (Pearson coefficient = 0.19, p = 0.12). In multiple regression analysis, reduced ABI was a predictor of elevated levels of AIx@75 (ß = -25.02, p < 0.01). CONCLUSIONS: Patients with CLI have high arterial stiffness measured by brachial artery oscillometry. The degree of limb ischemia, as measured by the ABI, is a predictor of increased AIx@75. The increased AIx@75 observed in CLI may have implications for the prognosis of this group of patients with advanced atherosclerosis.

CONTEXTO: A rigidez arterial aumentada está associada ao aumento da mortalidade cardiovascular. A relação entre rigidez arterial e isquemia crítica do membro (IC) não está bem estabelecida. OBJETIVOS: O objetivo deste estudo é analisar a relação entre índices de rigidez arterial e o grau de isquemia de membro medido pelo índice tornozelo-braço (ITB). MÉTODOS: Foi feito um estudo transversal em pacientes com IC e controles. A rigidez arterial foi medida usando a oscilometria da artéria braquial. Os índices de rigidez arterial mensurados foram a velocidade de onda de pulso (VOP) e o índice de aumentação corrigido para a frequência cardíaca de 75 batimentos/min (AIx@75). Regressão linear múltipla foi aplicada para identificar preditores dos índices de rigidez arterial. RESULTADOS: Pacientes do grupo IC tiveram VOP (12,1±1,9 m/s vs. 10,1±1,9 m/s, p < 0,01) e AIx@75 (31,8±7,8% vs. 17,5±10,8%, p < 0,01) maiores que controles. Pressão sistólica central foi maior no grupo IC (129,2±18,4 mmHg vs. 115,2±13,1 mmHg, p < 0,01). Houve uma relação inversa entre o AIx@75 e o ITB (coeficiente de Pearson = 0,19, p = 0,12). A análise de regressão múltipla mostrou que o ITB reduzido foi um preditor de elevação do AIx@75 (ß = -25,02, p < 0,01). CONCLUSÕES: Pacientes com IC têm elevada rigidez arterial medida por oscilometria da artéria braquial. O grau de isquemia do membro, medido pelo ITB, é um preditor do AIx@75 elevado. O aumento do AIx@75 na IC pode ter implicações de prognóstico no grupo de pacientes com aterosclerose avançada.

Aortic pulse wave analysis and functional capacity of heart transplantation candidates: a pilot study.

We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

Impact of social isolation during COVID-19 on anthropometric data, quality of life, baseline physical activity and aortic pulse wave parameters in children and adolescents in two independent samples.

BACKGROUND: The social restrictions resulting from the COVID-19 pandemic had a great impact on the routine of children and adolescents, with important consequences such as sleep, eating, and psychological/psychiatric disorders. Even though there are no studies on the subject, it is possible that these changes in habit and routine have also affected arterial stiffness (AS) in this population, which is an important predictor of cardiovascular risk. This study aimed to assess possible changes in AS, anthropometry, and quality of life (QoL) resulting from the COVID-19 pandemic in children and adolescents. METHODS: A controlled observational cross-sectional study was performed with 193 children and adolescents aged 9 to 19 years, allocated into two groups: before the pandemic (BPG) and one year after the pandemic (APG), matched by age and sex. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main AS indices evaluated were the augmentation index (AIx) and pulse wave velocity (PWV) derived from the aortic pulse wave. QoL was assessed using the Paediatric Quality of Life Inventory version 4.0 (PedsQL 4.0). RESULTS: Regarding QoL, the APG showed a worsening in emotional (p = 0.002) and school-related (p = 0.010) aspects. There was no statistically significant difference for most anthropometric parameters, except for the hip circumference, which was higher in the APG group (p < 0.001). The main predictor of AS in the paediatric population, AIx@75, was shown to be increased in the APG group (p < 0.001). Other cardiovascular parameters were also different, such as peripheral (p = 0.002) and central (p = 0.003) diastolic blood pressure, stroke volume (p = 0.010), and total vascular resistance (p = 0.002), which were shown to be decreased in the APG group, while the heart rate was increased (p < 0.001). CONCLUSIONS: Our results show that routine changes resulting from the period of social isolation increased cardiovascular risk in children and adolescents, evident by the increase in AIx@75, which is considered to be an important marker of cardiovascular risk in the paediatric population.

Improved lipid and glucose metabolism in transgenic rats with increased circulating angiotensin-(1-7).

OBJECTIVE: Obesity and diabetes remain among the world's most pervasive health problems. Although the importance of angiotensin II for metabolic regulation is well documented, the role of the angiotensin-(1-7)/Mas axis in this process is poorly understood. The aim of this study was to evaluate the effect of increased angiotensin-(1-7) plasma levels in lipid and glucose metabolism using transgenic rats that express an angiotensin-(1-7)-releasing fusion protein, TGR(A1-7)3292 (TGR). METHODS AND RESULTS: The increased angiotensin-(1-7) levels in TGR induced enhanced glucose tolerance, insulin sensitivity, and insulin-stimulated glucose uptake. In addition, TGR presented decreased triglycerides and cholesterol levels, as well as a significant decrease in abdominal fat mass, despite normal food intake. These alterations were accompanied by a marked decrease of angiotensinogen expression and increased Akt in adipose tissue. Furthermore, augmented plasma levels and expression in adipose tissue was observed for adiponectin. Accordingly, angiotensin-(1-7) stimulation increased adiponectin production by primary adipocyte culture, which was blocked by the Mas antagonist A779. Circulating insulin and muscle glycogen content were not altered in TGR. CONCLUSION: These results show that increased circulating angiotensin-(1-7) levels lead to prominent changes in glucose and lipid metabolism.

Asthma: role of the angiotensin-(1-7)/Mas (MAS1) pathway in pathophysiology and therapy.

The incidence of asthma is a global health problem and requires studies aimed for the development of new treatments to improve its clinical management, reducing personal and economic burdens on the health system. Therefore, the discovery of mediators that promote anti-inflammatory and pro-resolutive effects are highly desirable to improve lung function and quality of life of asthmatic patients. In that regard, experimental studies have shown that the angiotensin-(1-7)/Mas receptor (MAS1) of the renin-angiotensin system is a potential candidate for the treatment of asthma. Therefore, we have reviewed findings related to the function of the angiotensin-(1-7)/Mas pathway in regulating the processes associated with inflammation, including leukocyte influx, fibrogenesis, pulmonary dysfunction and the resolution of inflammation in asthma. Thus, a knowledge of the role of the angiotensin-(1-7)/Mas can help pave the way for the development of new treatments for this disease, which has high morbidity and mortality, through new types of experiments and clinical trials.

Effects of sepsis-induced acute lung injury on glycogen content in different tissues.

The metabolic profile is very affected in sepsis, which is the most important cause of extrapulmonary acute lung injury (ALI-EX). The aim of the present study was to investigate whether sepsis-induced ALI-EX in mice affects the glycogen content in different tissues. This measurement could indicate performance limitations of tissues and constitute a novel biochemical aspect of ALI. ALI was induced by cecal ligation and puncture (CLP), which is a model that reproduces clinical and pathological alterations stemming from sepsis. Control group mice were sham-operated. Glycogen content (mg/g tissue) from different tissues was measured using the anthrone reagent. Glycogen content in the diaphragm (0.3 +/- 0.1) and gastrocnemius muscle (0.4 +/- 0.1) was lower in the sepsis group than the control group (0.9 +/- 0.1 and 1.1 +/- 0.2, respectively). However, there were no significant differences in glycogen content in the heart and kidney. Sepsis caused a greater thickening of the alveolar walls, more areas of atelectasis, and a greater abundance of inflammatory cells in comparison to the control group. These results demonstrate that glycogen content in sepsis-induced ALI-EX is altered in different tissues.

Echocardiographic Assessment of Ventricular Function in Young Patients with Asthma.

BACKGROUND: Despite significant advances in understanding the pathophysiology and management of asthma, some of systemic effects of asthma are still not well defined. OBJECTIVES: To compare heart function, baseline physical activity level, and functional exercise capacity in young patients with mild-to-moderate asthma and healthy controls. METHODS: Eighteen healthy (12.67 ± 0.39 years) and 20 asthmatics (12.0 ± 0.38 years) patients were enrolled in the study. Echocardiography parameters were evaluated using conventional and tissue Doppler imaging (TDI). RESULTS: Although pulmonary acceleration time (PAT) and pulmonary artery systolic pressure (PASP) were within normal limits, these parameters differed significantly between the control and asthmatic groups. PAT was lower (p < 0.0001) and PASP (p < 0.0002) was higher in the asthma group (114.3 ± 3.70 ms and 25.40 ± 0.54 mmHg) than the control group (135.30 ± 2.28 ms and 22.22 ± 0.40 mmHg). The asthmatic group had significantly lower early diastolic myocardial velocity (E', p = 0.0047) and lower E' to late (E'/A', p = 0.0017) (13.75 ± 0.53 cm/s and 1.70 ± 0.09, respectively) compared with control group (15.71 ± 0.34 cm/s and 2.12 ± 0.08, respectively) at tricuspid valve. In the lateral mitral valve tissue Doppler, the asthmatic group had lower E' compared with control group (p = 0.0466; 13.27 ± 0.43 cm/s and 14.32 ± 0.25 cm/s, respectively), but there was no statistic difference in the E'/A' ratio (p = 0.1161). Right isovolumetric relaxation time was higher (p = 0.0007) in asthmatic (57.15 ± 0.97 ms) than the control group (52.28 ± 0.87 ms), reflecting global myocardial dysfunction. The right and left myocardial performance indexes were significantly higher in the asthmatic (0.43 ± 0.01 and 0.37 ± 0.01, respectively) compared with control group (0.40 ± 0.01 and 0.34 ± 0.01, respectively) (p = 0.0383 and p = 0.0059, respectively). Physical activity level, and distance travelled on the six-minute walk test were similar in both groups. CONCLUSION: Changes in echocardiographic parameters, evaluated by conventional and TDI, were observed in mild-to-moderate asthma patients even with normal functional exercise capacity and baseline physical activity level. Our results suggest that the echocardiogram may be useful for the early detection and evoluation of asthma-induced cardiac changes.

Qualidade de vida e índices de rigidez arterial em pacientes com isquemia crônica ameaçadora ao membro / Quality of life and arterial stiffness indices in patients with chronic limb-threatening ischemia

Introdução: Os fatores associados ao comprometimento da qualidade de vida em pacientes com isquemia crônica ameaçadora ao membro não estão bem estabelecidos. Objetivo: Verificar se existe associação entre a qualidade de vida e os índices de rigidez arterial, velocidade de onda de pulso (VOP) e o índice de aumentação normalizado para a frequência cardíaca de 75 bpm (AIx@75). Métodos: Trata-se de um estudo transversal, observacional, com a participação de 17 pacientes (65,65 ±11,79 anos) com isquemia crônica ameaçadora ao membro definida pela classificação de Rutherford 4, 5 e 6, e com o índice tornozelo-braço (ITB) < 0,80. A avaliação dos parâmetros vasculares e os índices de rigidez arterial foram realizadas com o aparelho Mobil-O-Graph ® que gera a onda de pulso aórtica a partir da oscilometria da artéria braquial. A qualidade de vida foi avaliada pelo questionário Vascular quality of life questionaire (VascuQoL-6), versão curta, desenvolvido especificamente para avaliar pacientes com comprometimento circulatório, arterial ou venoso. Resultados: Os valores do ITB e do escore de qualidade de vida foram 0,48 ± 0,14 e 15,88 ± 1,03; respectivamente. Dos 17 pacientes, 12 apresentavam hipertensão arterial sistólica e dezesseis apresentaram a VOP maior que 10 m/s. Não foram observadas correlações entre o escore de qualidade de vida com o AIx@75 (p=0,54 e r=0,16), a VOP (p=0,332 e r=0,248) e o ITB (p=0,707 e r=0,098). Conclusão: O presente estudo demonstrou que pacientes com isquemia crônica ameaçadora ao membro apresentam comprometimento importante da qualidade de vida sem associação com os índices de rigidez arterial e ITB.

Introduction: The factors associated with impaired quality of life in patients with chronic limb-threatening ischemia are not well established. Objective: Check whether there is an association between quality of life and arterial stiffness indexes, pulse wave velocity (PWV) and the augmentation index corrected to 75 beats per minute heart rate (AIx@75). Methods: This is a cross-sectional, observational study, with the participation of 17 patients (65.65 ± 11.79 years) with chronic limb-threatening ischemia defined by the Rutherford classification 4, 5 and 6, and with the ankle-arm index (ABI) < 0.80. The evaluation of vascular parameters and arterial stiffness indeces was performed with the MobilO-Graph ® device that generates the aortic pulse wave from the brachial artery oscillometry. Quality of life was assessed using the questionnaire Vascular quality of life questionaire (VascuQoL-6), short version, developed specifically to evaluate patients with circulatory, arterial or venous involvement. Results: The values of the ITB and the quality of life score were 0.48 ± 0.14 and 15.88 ± 1.03; respectively. Of the 17 patients, 12 had systolic arterial hypertension and sixteen had PWV greater than 10 m / s. No correlations were observed between the quality of life score with AIx @ 75 (p = 0.54 and r = 0.16), PWV (p = 0.332 and r = 0.248) and ABI (p = 0.707 and r = 0.098). Conclusion: The present study demonstrated that patients with chronic limb-threatening ischemia present significant impairment of quality of life without association with arterial stiffness and ABI.

Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis.

The interstitial lung diseases are poorly understood and there are currently no studies evaluating the association of physical exercise with an ACE2 activator (DIZE) as a possible treatment for this group of diseases. We evaluate the effects of pharmacological treatment with an angiotensin-converting enzyme 2 activator drug, associated with exercise, on the pulmonary lesions induced by bleomycin. From the 96 male Balb/c mice used in the experiment, only 49 received 8 U/kg of bleomycin (BLM, intratracheally). The mice were divided into control (C) and bleomycin (BLM) groups, sedentary and trained (C-SED, C-EXE, BLM-SED, BLM-EXE), control and bleomycin and also sedentary and trained treated with diminazene (C-SED/E, C-EXE/E, BLM-SED/E, BLM-EXE/E). The animals were trained five days/week, 1 h/day with 60% of the maximum load obtained in a functional capacity test, for four weeks. Diminazene groups were treated (1 mg/kg, by gavage) daily until the end of the experiment. The lungs were collected 48 h after the training program, set in buffered formalin and investigated by Gomori's trichrome, immunohistochemistry of collagen type I, TGF-ß1, beta-prolyl-4-hydroxylase, MMP-1 and -2. The BLM-EXE/E group obtained a significant increase in functional capacity, reduced amount of fibrosis and type I collagen, decreased expression of TGF-ß1 and beta-prolyl-4-hydroxylase and an increase of metalloproteinase -1, -2 when compared with the other groups. The present research shows, for the first time, that exercise training associated with the activation of ACE2 potentially reduces pulmonary fibrosis.

Aplicabilidade dos marcadores de rigidez arterial na doença arterial periférica / Applications of arterial stiffness markers in peripheral arterial disease

A análise de rigidez arterial tem sido feita em vários grupos populacionais com o objetivo de identificar precocemente o risco cardiovascular e realizar medidas terapêuticas específicas. O aumento da rigidez arterial leva à perda de capacidade de adaptação da aorta e das artérias elásticas às variações de pressão durante o ciclo cardíaco. Os principais marcadores de rigidez arterial são a velocidade de onda de pulso (VOP), o índice de aumentação (AIx) e a pressão aórtica central. Esses índices podem ser obtidos de maneira não invasiva. Ocorre aumento da mortalidade em pacientes com doença coronariana ou em hemodiálise que apresentam aumento da VOP ou do AIx. A associação com a doença arterial periférica é pouco estudada. O objetivo desta revisão é mostrar a aplicabilidade e a utilidade de realizar medidas de rigidez arterial em pacientes com doença arterial periférica

Arterial stiffness has been analyzed in many different population groups with the objective of identifying cardiovascular risk early and performing specific therapeutic interventions. Increased arterial stiffness affects the capacity of the aorta and elastic arteries to adapt to pressure variations during the cardiac cycle. The main markers of arterial stiffness are pulse wave velocity (PWV), augmentation index (AIx) and central aortic pressure. They can be measured noninvasively. Patients with coronary disease or on hemodialysis who have elevated PWV or AIx have increased mortality. The association with peripheral arterial disease has been studied little. The objective of this review is to demonstrate the applicability and utility of assessing measures of arterial stiffness in patients with peripheral arterial disease

Association between critical limb ischemia and arterial stiffness measured by brachial artery oscillometry / Associação entre isquemia crítica do membro e rigidez arterial medida por oscilometria da artéria braquial

Background Elevated arterial stiffness is associated with increased cardiovascular mortality. The relationship between arterial stiffness and critical limb ischemia (CLI) is not well established. Objectives The objective of this study is to analyze the relationship between arterial stiffness indices and the degree of limb ischemia measured by the ankle-brachial index (ABI). Methods A cross-sectional study comparing patients with CLI and controls. Arterial stiffness was measured using brachial artery oscillometry. The arterial stiffness indices pulse wave velocity (PWV) and augmentation index normalized to 75 beats/min (AIx@75) were determined. Multiple linear regression was applied to identify predictors of arterial stiffness indices. Results Patients in the CLI group had higher PWV (12.1±1.9 m/s vs. 10.1±1.9 m/s, p < 0.01) and AIx@75 (31.8±7.8% vs. 17.5±10.8%, p < 0.01) than controls. Central systolic pressure was higher in the CLI group (129.2±18.4 mmHg vs. 115.2±13.1 mmHg, p < 0.01). There was an inverse relationship between AIx@75 and ABI (Pearson coefficient = 0.24, p = 0.048), but there was no relationship between ABI and PWV (Pearson coefficient = 0.19, p = 0.12). In multiple regression analysis, reduced ABI was a predictor of elevated levels of AIx@75 (β = -25.02, p < 0.01). Conclusions Patients with CLI have high arterial stiffness measured by brachial artery oscillometry. The degree of limb ischemia, as measured by the ABI, is a predictor of increased AIx@75. The increased AIx@75 observed in CLI may have implications for the prognosis of this group of patients with advanced atherosclerosis

A rigidez arterial aumentada está associada ao aumento da mortalidade cardiovascular. A relação entre rigidez arterial e isquemia crítica do membro (IC) não está bem estabelecida. Objetivos O objetivo deste estudo é analisar a relação entre índices de rigidez arterial e o grau de isquemia de membro medido pelo índice tornozelo-braço (ITB). Métodos Foi feito um estudo transversal em pacientes com IC e controles. A rigidez arterial foi medida usando a oscilometria da artéria braquial. Os índices de rigidez arterial mensurados foram a velocidade de onda de pulso (VOP) e o índice de aumentação corrigido para a frequência cardíaca de 75 batimentos/min (AIx@75). Regressão linear múltipla foi aplicada para identificar preditores dos índices de rigidez arterial. Resultados Pacientes do grupo IC tiveram VOP (12,1±1,9 m/s vs. 10,1±1,9 m/s, p < 0,01) e AIx@75 (31,8±7,8% vs. 17,5±10,8%, p < 0,01) maiores que controles. Pressão sistólica central foi maior no grupo IC (129,2±18,4 mmHg vs. 115,2±13,1 mmHg, p < 0,01). Houve uma relação inversa entre o AIx@75 e o ITB (coeficiente de Pearson = 0,19, p = 0,12). A análise de regressão múltipla mostrou que o ITB reduzido foi um preditor de elevação do AIx@75 (β = -25,02, p < 0,01). Conclusões Pacientes com IC têm elevada rigidez arterial medida por oscilometria da artéria braquial. O grau de isquemia do membro, medido pelo ITB, é um preditor do AIx@75 elevado. O aumento do AIx@75 na IC pode ter implicações de prognóstico no grupo de pacientes com aterosclerose avançada

Paraquat poisoning induces TNF-α-dependent iNOS/NO mediated hyporesponsiveness of the aorta to vasoconstrictors in rats.

Paraquat is a toxic herbicide that may induce acute lung injury, circulatory failure and death. The present work aimed at investigating whether there is systemic inflammation and vascular dysfunction after paraquat exposure and whether these parameters were related. There was neutrophilia and accumulation of neutrophils in lung and bronchoalveolar lavage of animals given paraquat. This was associated with an increase in serum levels of TNF-α. In rats given paraquat, the relaxant response of aortic rings to acetylcholine was not modified but the contractile response to phenylephrine was greatly reduced. Endothelium removal or treatment with non-selective (L-NAME) or selective (L-NIL) inhibitors of inducible nitric oxide synthase (iNOS) restored contraction of aortas. There was greater production of nitric oxide (NO), which was restored to basal level by L-NIL, and greater expression of iNOS in endothelial cells, as seen by Western blot analyses and confocal microscopy. Blockade of TNF-α reduced pulmonary and systemic inflammation and vascular dysfunction. Together, our results clearly show that paraquat causes pulmonary and systemic inflammation, and vascular dysfunction in rats. Vascular dysfunction is TNF-α dependent, associated with enhanced expression of iNOS in aortic endothelial cells and greater NO production, which accounts for the decreased responsiveness of aortas to vasoconstrictors. Blockers of TNF-α may be useful in patients with paraquat poisoning.