Brazilian Portuguese version and content validity of the Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH).

INTRODUCTION: The Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH) program is a personalized, progressive 12-week exercise program for people with hand problems due to rheumatoid arthritis (RA). Patients are provided with two guidance documents, the 'Patient Exercise Booklet' and the 'Personal Exercise Guide', to continue the exercises independently at home. OBJECTIVE: This study aimed to translate and culturally adapt the SARAH protocol into Brazilian Portuguese and validate its content. METHODS: The guidance documents 'Patient Exercise Booklet' and 'Personal Exercise Guide' of the SARAH program were translated and culturally adapted to Brazilian Portuguese. The content validity was obtained by calculating the content validity index (CVI). RESULTS: The Brazilian version of the SARAH protocol reached semantic, idiomatic, conceptual, and cultural equivalences. The CVI was greater than 0.8, corresponding to a satisfactory index. The verbal comprehension was 4.9, showing good verbal comprehension of the target population. CONCLUSION: The Brazilian Portuguese version of the SARAH protocol is available to Brazilian people with compromised hands due to RA with satisfactory content validity.

Brazilian Portuguese version and content validity of the Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH)

Abstract Introduction The Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH) program is a personalized, progressive 12-week exercise program for people with hand problems due to rheumatoid arthritis (RA). Patients are provided with two guidance documents, the 'Patient Exercise Booklet' and the 'Personal Exercise Guide', to continue the exercises independently at home. Objective This study aimed to translate and culturally adapt the SARAH protocol into Brazilian Portuguese and validate its content. Methods The guidance documents 'Patient Exercise Booklet' and 'Personal Exercise Guide' of the SARAH program were translated and culturally adapted to Brazilian Portuguese. The content validity was obtained by calculating the content validity index (CVI). Results The Brazilian version of the SARAH protocol reached semantic, idiomatic, conceptual, and cultural equivalences. The CVI was greater than 0.8, corresponding to a satisfactory index. The verbal comprehension was 4.9, showing good verbal comprehension ofthe target population. Conclusion The Brazilian Portuguese version of the SARAH protocol is available to Brazilian people with compromised hands due to RA with satisfactory content validity.

The impact of Chikungunya chronic arthralgia on women's upper limbs motor function: a cross-sectional study / O impacto da artralgia crônica pós-Chikungunya na função motora dos membros superiores de mulheres: um estudo transversal / El impacto de la artralgia crónica poschikunguña en la función motora del miembro superior de mujeres: un estudio transversal

ABSTRACT Post-Chikungunya chronic arthralgia (PCCA) may lead to musculoskeletal repercussions and functional loss. The objective was to assess the upper limb physical disability and symptoms during daily, work, and leisure activities of women presenting PCCA compared to healthy controls (HC). This was a cross-sectional study conducted with 52 women. The participants were divided into PCCA (37) and HC (15) groups. Handgrip strength, range of motion, level of pain (numerical rating scale), and participants' physical disability and symptoms (Disabilities of the Arm, Shoulder, and Hand Questionnaire - DASH) were evaluated. Differences between groups were evaluated using the Students t-test and Pearson's correlations. The chi-square test was applied for categorical variables. The significance was set at α=0.05. The disease duration was 19.5±13.1 months. We found no differences between groups for peak force (PCAA:23.6±7.4kgf; HC: 24.5±6.2kgf; p=0.676). The results showed a significant difference between groups regarding range of motion (PCCA: 63.5±17.3o; HC: 77.2±9.6o), level of hand pain (PCCA: 5.8±2.2; HC: 0.4±1.5), and upper limbs functional levels (PCCA: 44.5±17.4; HC: 16.2±20.5). Participants related severe difficulty or inability to perform tasks such as opening a jar (78.4%), placing objects above head height (48.7%), doing heavy household chores (56.8%), and gardening (51.4%). Impairment in the upper limb physical function in daily, work, and leisure activities shows the higher prevalence in the long-term.

RESUMO A artralgia crônica pós-Chikungunya (ACPC) pode gerar repercussões musculoesqueléticas e perda funcional. Nesse sentido, o objetivo deste estudo foi avaliar a incapacidade física e os sintomas de membros superiores de mulheres com ACPC durante atividades diárias, laborais e de lazer comparadas aos controles saudáveis (CS). Para tanto, realizou-se um estudo transversal conduzido com 52 mulheres. As participantes foram divididas entre os grupos com ACPC (37) e CS (15). Foram avaliados força de preensão, amplitude de movimento (ADM), nível de dor (escala numérica de dor) e incapacidade física e sintomas por meio do Disabilities of the Arm, Shoulder and Hand Questionnaire (Dash). Diferenças entre os grupos foram avaliadas pelo teste t de Student e correlações de Pearson. O teste qui-quadrado foi utilizado para variáveis categóricas e α=0,05 foi estabelecido como nível de significância. Verificou-se que a duração da ACPC foi de 19,5±13,1 meses. Não houve diferença entre os grupos para a força pico (ACPC: 23,6±7,4kgf; CS: 24,5±6,2kgf; p=0,676). Os resultados demonstraram diferença significativa entre os grupos em termos de ADM (ACPC: 63,5±17,3o; CS: 77,2±9,6o), nível de dor nas mãos (ACPC: 5,8±2,2; CS: 0,4±1,5) e níveis funcionais dos membros superiores (ACPC: 44,5±17,4; CS: 16,2±20,5). As participantes relataram extrema dificuldade ou incapacidade para realizar tarefas como abrir um pote (78,4%), colocar objetos em um local acima da cabeça (48,7%), realizar atividades domésticas pesadas (56,8%) e atividades de jardinagem (51,4%). Conclui-se que a função física dos membros superiores durante as atividades diárias, laborais e de lazer constitui o maior comprometimento apresentado a longo prazo.

RESUMEN La artralgia crónica poschikunguña (ACPC) puede tener como efecto repercusiones musculoesqueléticas y pérdida funcional. En este sentido, el objetivo de este estudio fue evaluar la discapacidad física y los síntomas de miembros superiores de mujeres con ACPC durante las actividades diarias, laborales y de ocio en comparación con controles sanos (CS). Por ello, se realizó un estudio transversal con 52 mujeres. Las participantes se dividieron en los grupos ACPC (37) y CS (15). La fuerza de agarre, el rango de movimiento (ROM), el nivel de dolor (escala numérica de dolor), la discapacidad física y los síntomas se evaluaron mediante el Disabilities of the Arm, Shoulder and Hand Questionnaire (Dash). Las diferencias entre los grupos se evaluaron con la aplicación de la prueba t de Student y las correlaciones de Pearson. Se utilizó la prueba de chi-cuadrado para las variables categóricas y se estableció como nivel de significación α=0,05. Se encontró que la duración de la ACPC fue de 19,5±13,1 meses. No hubo diferencia entre los grupos para la fuerza máxima (ACPC: 23,6±7,4kgf; CS: 24,5±6,2kgf; p=0,676). Los resultados mostraron una diferencia significativa entre los grupos respecto al ROM (ACPC: 63,5±17,3o; CS: 77,2±9,6o), el nivel de dolor en la mano (ACPC: 5,8±2,2; CS: 0,4±1,5) y los niveles funcionales de miembros superiores (ACPC: 44,5±17,4; CS: 16,2±20,5). Las participantes informaron una extrema dificultad o incapacidad para realizar tareas como abrir un frasco (78,4%), poner objetos en un lugar más alto (48,7%), realizar actividades domésticas pesadas (56,8%) y actividades de jardinería (51,4%). Se concluyó que la función física de los miembros superiores durante las actividades diarias, laborales y de ocio constituye el mayor compromiso a largo plazo.

Pain, balance, grip strength and gait parameters of older adults with and without post-chikungunya chronic arthralgia.

OBJECTIVE: To compare the levels of pain, grip strength, balance and gait in older adults with and without post-Chikungunya chronic arthralgia (PCCA). METHODS: Sixty-two older adults, 30 with and 32 without PCCA participated in the study. Pain level was assessed using a Visual Analogue Scale (VAS). Gait during a 10-m walk was assessed using inertial sensors. Semi-static balance was assessed during an eyes-closed bipedal balance test on a force platform, and grip strength was assessed using a hand dynamometer. RESULTS: Participants with PCCA presented severe levels of pain (VAS > 7.5), poorer balance, lower grip strength, walked slower, with lower cadence and stride length and higher stride time and stride length variability than participants without PCCA (P < 0.001 for all variables). CONCLUSIONS: Older adults with PCCA had high levels of pain, impaired balance and gait and lower grip strength compared to older adults without PCCA.

Adherence to physical activity in adults with chronic diseases: ELSA-Brasil.

OBJECTIVE: The objective of this study is to investigate the adherence and the factors that influence adherence to physical activity in adults with dyslipidemia, hypertension, or diabetes. METHODS: The analyses were based on data collected at the baseline of the 14,521 participants from the study ELSA-Brasil aged between 35 and 74 years. The level of leisure time physical activity was determined using the International Physical Activity Questionnaire. Logistic regression analyses were performed to examine the influence of the demographic data, socioeconomic conditions, perceived health status, and access to exercise facilities in the neighborhood on adherence to physical activity. RESULTS: Men with hypertension and dyslipidemia were more active than women. The results show that 17.8%, 15.1%, and 13.9% of the subjects who reported dyslipidemia, hypertension, and diabetes, respectively, adhere to the physical activity recommendations. The factors positively associated with adherence were higher education and income. Older individuals who reported poor perceived health, were overweight and obese, regularly smoked, and had fewer opportunities to exercise in the neighborhood presented lower adherence. CONCLUSIONS: The number of adults with dyslipidemia, hypertension, and diabetes who adhere to the physical activity recommendations is very low. Higher education and income are positively associated with adherence, while age, excess body weight, negative perceived health, regular smoking, and lack of opportunity to exercise in the neighborhood were considered barriers to physical activity.

Influence of Long-Term Salt Diets on Cardiac Ca2+ Handling and Contractility Proteins in Hypertensive Rats.

BACKGROUND: High sodium intake contributes to the pathogenesis of hypertension and adversely affects cardiac function. Conversely, sodium reduction is associated with a blood pressure decrease and improved cardiovascular function. However, the mechanisms that underlie the cardiac effects induced by salt intake in hypertension have not been fully elucidated. Ca2+ handling is critical for efficient myocardial function; thus, we aimed to investigate the long-term effects of diets with different salt contents on cardiac function and Ca2+ handling proteins in spontaneously hypertensive rats (SHRs). METHODS: Cardiac function was evaluated by catheterization. Ca2+ handling and contractile proteins were evaluated by immunoblotting in hearts from SHRs fed for 6 months with diets containing high (HS, 3%), low (LS, 0.03%), or normal salt content (NS, 0.3%). Diets were introduced immediately after weaning. Tail cuff pletismography was assessed at the 3rd and 7th months of follow-up. RESULTS: Compared to the NS group, the HS group exhibited worsened hypertension, increased cardiac expression of ß-myosin heavy chain (MHC), a decreased α/ß-MHC ratio and reduced expression of both phospholamban (PLB) and Na+/Ca2+ exchanger (NCX). LS intake attenuated the blood pressure increase and left ventricle hypertrophy, slightly decreased the cardiac contractility and relaxation index, and increased the α/ß-MHC ratio. These effects were accompanied by increased cardiac PLB expression and decreased Ca2+ L-type channel and NCX expression. CONCLUSIONS: These findings indicate that the modulation of Ca2+ handling may be one of the molecular mechanisms underlying the effect of salt intake on myocardial function in hypertension.

Xanthine Oxidase Activation Modulates the Endothelial (Vascular) Dysfunction Related to HgCl2 Exposure Plus Myocardial Infarction in Rats.

Heavy metal exposure is associated with cardiovascular diseases such as myocardial infarction (MI). Vascular dysfunction is related to both the causes and the consequences of MI. We investigated whether chronic exposure to low doses of mercury chloride (HgCl2) worsens MI-induced endothelial dysfunction 7 days after MI. Male Wistar rats were divided into four groups: Control (vehicle), HgCl2 (4 weeks of exposure), surgically induced MI and combined HgCl2-MI. Morphological and hemodynamic measurements were used to characterize the MI model 7 days after the insult. Vascular reactivity was evaluated in aortic rings. Chronic HgCl2 exposure did not cause more heart injury than MI alone in terms of the morphological or hemodynamic parameters. Vascular reactivity increased in all groups, but the combination of HgCl2-MI increased the vasorelaxation induced by ACh compared with the HgCl2 and MI groups. Results showed reduced endothelial nitric oxide synthase (eNOS) protein expression in the MI group; increased iNOS activity in the HgCl2-MI group, although without enough magnitude to reverse the reduction in NO bioavailability; and increased phenylephrine response in the HgCl2-MI group due to an increase in ROS production, notably via xanthine oxidase (XO). Results suggest that the combination of 1 month pre-exposure of HgCl2 before MI changed the endothelial generation of oxidative stress induced by mercury exposure from NADPH oxidase pathway to XO (xanthine oxidase)-dependent ROS production.

Adherence to physical activity in adults with chronic diseases: ELSA-Brasil

ABSTRACT OBJECTIVE The objective of this study is to investigate the adherence and the factors that influence adherence to physical activity in adults with dyslipidemia, hypertension, or diabetes. METHODS The analyses were based on data collected at the baseline of the 14,521 participants from the study ELSA-Brasil aged between 35 and 74 years. The level of leisure time physical activity was determined using the International Physical Activity Questionnaire. Logistic regression analyses were performed to examine the influence of the demographic data, socioeconomic conditions, perceived health status, and access to exercise facilities in the neighborhood on adherence to physical activity. RESULTS Men with hypertension and dyslipidemia were more active than women. The results show that 17.8%, 15.1%, and 13.9% of the subjects who reported dyslipidemia, hypertension, and diabetes, respectively, adhere to the physical activity recommendations. The factors positively associated with adherence were higher education and income. Older individuals who reported poor perceived health, were overweight and obese, regularly smoked, and had fewer opportunities to exercise in the neighborhood presented lower adherence. CONCLUSIONS The number of adults with dyslipidemia, hypertension, and diabetes who adhere to the physical activity recommendations is very low. Higher education and income are positively associated with adherence, while age, excess body weight, negative perceived health, regular smoking, and lack of opportunity to exercise in the neighborhood were considered barriers to physical activity.

Chronic fructose intake accelerates non-alcoholic fatty liver disease in the presence of essential hypertension.

BACKGROUND: The growing epidemic of metabolic syndrome has been related to the increased use of fructose by the food industry. In fact, the use of fructose as an ingredient has increased in sweetened beverages, such as sodas and juices. We thus hypothesized that fructose intake by hypertensive rats would have a worse prognosis in developing metabolic disorder and non-alcoholic fatty liver disease. METHODS: Male Wistar and SHR rats aged 6weeks were given water or fructose (10%) for 6weeks. Blood glucose was measured every two weeks, and insulin and glucose sensitivity tests were assessed at the end of the follow-up. Systolic blood pressure was measure by plethysmography. Lean mass and abdominal fat mass were collected and weighed. Liver tissue was analyzed to determine interstitial fat deposition and fibrosis. RESULTS: Fasting glucose increased in animals that underwent a high fructose intake, independent of blood pressure levels. Also, insulin resistance was observed in normotensive and mostly in hypertensive rats after fructose intake. Fructose intake caused a 2.5-fold increase in triglycerides levels in both groups. Fructose intake did not change lean mass. However, we found that fructose intake significantly increased abdominal fat mass deposition in normotensive but not in hypertensive rats. Nevertheless, chronic fructose intake only increased fat deposition and fibrosis in the liver in hypertensive rats. CONCLUSIONS: We demonstrated that, in normotensive and hypertensive rats, fructose intake increased triglycerides and abdominal fat deposition, and caused insulin resistance. However, hypertensive rats that underwent fructose intake also developed interstitial fat deposition and fibrosis in liver.

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats.

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.

Effects of high and low salt intake on left ventricular remodeling after myocardial infarction in normotensive rats.

The dietary-sodium restriction is a standard approach following an acute myocardial infarction (MI). We examined the hypothesis in which the use of a high or low-sodium diet would worsen post-infarction left ventricular remodeling in rats and facilitate the development of heart failure. Left coronary artery ligation or sham-operated (SO) was produced in male Wistar rats (250-290 g). After surgery, animals were assigned to one of the three diets: standard amount of sodium (0.3% NaCl, SO and MI groups), a high-sodium diet (0.6% NaCl, SO-High and MI-High groups), or a low-sodium diet (0.03% NaCl, SO-Low and MI-Low groups). Diets were provided for 8 weeks post-surgery. Mortality rate was elevated in high-salt group (MI-Low, 21.4%; MI, 35.3%; MI-High, 47.6%). Contractility parameter was seen to be impaired in MI-Low animals (3195 ± 211 mm Hg/s) compared with MI (3751 ± 200 mm Hg/s). Low-salt diet did not prevent myocardial collagen deposition (MI-Low, 5.2 ± 0.5%; MI, 5.0 ± 0.4%) nor myocyte hypertrophy (MI-Low, 608 ± 41µ(2); MI, 712 ± 53 µm(2)) in left ventricle after MI. High-salt intake increases collagen volume fraction (SO, 3.3 ± 0.4%; SO-High, 4.7 ± 0.4%) in animals sham, but no major changes after MI. Our results show that ventricular remodeling was not altered by immediate introduction of low sodium after MI, and it may be a safe strategy as a therapeutic intervention to avoid volume retention. However, high sodium can be harmful, accelerating the post-infaction ventricular remodeling.

High potassium intake blunts the effect of elevated sodium intake on blood pressure levels.

The purpose of this study was to investigate the influence of dietary potassium on the sodium effect on blood pressure (BP) in the general population and the adherence of current recommendations for sodium and potassium intake. An overnight (12-hour) urine sample was collected in a population-based study to investigate cardiovascular risk. A sub-sample of 1285 subjects (age range, 25-64 years) free from any medication interfering with BP or potassium excretion was studied. Of the participants, 86.0% consumed over 6 g of salt/day and 87.7% less than the recommended intake of potassium (4.7 g). Potassium excretion and the sodium to potassium ratio were significantly related to systolic and diastolic BP only in subjects consuming more than 6 g/day of salt. Subjects in the highest sodium to potassium ratio quartile (surrogate of unhealthy diet) presented 8 mm Hg and 7 mm Hg higher values of systolic and diastolic BP, respectively, when compared with the first quartile, while individuals in the fourth quartile of urinary potassium excretion (healthier diet) showed 6 mm Hg and 4 mm Hg lower systolic and diastolic BP, respectively, compared with the first quartile. Our data indicate that when people have an increased intake of potassium, high intake of sodium is not associated with higher BP.

High salt intake does not produce additional impairment in the coronary artery relaxation of spontaneously hypertensive aged rats.

The effect of a salt-based diet on the coronary responsiveness in aged hypertensive rats (SHR) still is unclear. We investigated the effects of high salt intake on the relaxation properties of coronary arteries of aged SHRs. Male SHR (32 week-old) received drinking water (SHR) or 1% NaCl solution (SHR-Salt) for 8 weeks. Isolated coronary segments were subjected to concentration-response curves to acetylcholine (ACh) in the presence or absence of L-NAME (100 µM), enalaprilate (10 µM), losartan (10 µM), and spironolactone (100 µM). Salt intake did not increase blood pressure in old SHRs, but caused ventricular hypertrophy. The endothelium-dependent relaxation in SHRs was lower than in Wistar rats. However, salt intake did not add further impairment. Both enalaprilate and losartan reduced the vasodilator response in coronary arteries from Wistar, but did not affect SHR-salt rats. Conversely, losartan attenuated the impaired ACh relaxation observed in SHR. Spironolactone reduced the relaxation induced by ACh in coronary arteries from Wistar rats but not in SHR. The renin-angiotensin-aldosterone system participates in the impaired coronary relaxation in aged SHR, but does not partake in this deleterious effect under increased salt intake, indicating that age could differentiate the effects of high sodium intake in coronary arteries of SHR.

Carvedilol prevents ovariectomy-induced myocardial contractile dysfunction in female rat.

Carvedilol has beneficial effects on cardiac function in patients with heart failure but its effect on ovariectomy-induced myocardial contractile dysfunction remains unclear. Estrogen deficiency induces myocardial contractile dysfunction and increases cardiovascular disease risk in postmenopausal women. Our aim was to investigate whether carvedilol, a beta receptor blocker, would prevent ovariectomy-induced myocardial contractile dysfunction. Female rats (8 weeks old) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with carvedilol (OVX+CAR, 20 mg/kg), placebo (OVX) and SHAM for 58 days. Left ventricle papillary muscle was mounted for isometric tension recordings. The inotropic response to Ca(2+) (0.62 to 3.75 mM) and isoproterenol (Iso 10(-8) to 10(-2 )M) were assessed. Expression of calcium handling proteins was measured by western blot analysis. Carvedilol treatment in the OVX animals: prevented weight gain and slight hypertrophy, restored the reduced positive inotropic responses to Ca(2+) and isoproterenol, prevented the reduction in SERCA2a expression, abolished the increase in superoxide anion production, normalized the increase in p22(phox) expression, and decreased serum angiotensin converting enzyme (ACE) activity. This study demonstrated that myocardial contractile dysfunction and SERCA2a down regulation were prevented by carvedilol treatment. Superoxide anion production and NADPH oxidase seem to be involved in this response.

Kinetics of the electrocardiographic changes after permanent coronary occlusion in rats: Relationship with infarct size.

The electrocardiogram (ECG) has been a useful tool to identify ischemia in humans and laboratory animals. Previous ECG studies showed that presence of pathological Q waves in lead DI in rats submitted to ligature of the left coronary artery (LCA) is a good predictor of successful myocardial infarction (MI). This study aimed to determine the sensitivity and the specificity of these ECG findings to predict successful MI. Male Wistar rats were submitted to surgical ligature of the LCA (N=86) or sham-operation (SO, N=16). ECG was recorded under halothane/ether anesthesia before surgery and 1, 3, 5, 7, and 15 days later. MI was determined by the presence of a transmural fibrous scar. Sixty-nine rats survived and 60 showed fibrous scar indicating a successful production of MI (18 and 42 animals were analyzed 1 or 15 days after MI, respectively). Twenty-four hours after, Q amplitude was linearly related to infarct size (r=-0.778; P<0.01), but not 15 days after (r=-0.416; P>0.05). In 53 out of 60 rats with transmural scar, Q wave in lead DI was identified in the ECG. Absence of Q wave occurred in 7 animals. The sensitivity was 88% (CI(95)=83-93%). Nine animals submitted to coronary ligature did not show infarct scar. One of these animals, however, showed Q wave in DI, indicating a specificity of 77% (CI(95)=65-104%). In conclusion, ECG can be used as a reliable tool to identify MI and can be used to predict the infarct size as earlier as 1 day after LCA ligation in rats.

Granulocyte colony-stimulating factor improves early remodeling in isoproterenol-induced cardiac injury in rats.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has been used in some animal models and humans with well-established cardiovascular diseases. However, its effects in the initial stage of progressive non-ischemic heart failure are unknown. METHODS: Wistar rats (260-300 g) were divided into three groups: control (without any intervention), ISO (150 mg/kg isoproterenol hydrochloride sc, once a day for two consecutive days), and ISO-GCSF (50 µg/kg/d G-CSF for 7 days beginning 24 h after the last administration of ISO). Echocardiography was performed at baseline and after 30 days of follow-up. Subsequently, animals were anesthetized for hemodynamic analysis. The left ventricle was removed for analysis of interstitial collagen deposition and cardiomyocyte hypertrophy. RESULTS: Isoproterenol led to left ventricular dilation (control, 7.7 ± 0.14 mm; ISO, 8.7 ± 0.16 mm; ISO-GCSF 7.8 ± 0.09 mm; p < 0.05), myocardial fibrosis (control, 2.0 ± 0.18%; ISO, 9.1 ± 0.81%; ISO-GCSF 5.9 ± 0.58%; p < 0.05) and cardiomyocyte hypertrophy (control, 303 ± 10 µm(2); ISO, 356 ± 18 µm(2); ISO-GCSF 338 ± 11 µm(2); p < 0.05). However, G-CSF partially prevented collagen deposition and left ventricular enlargement, with a slight effect on hypertrophy. Characterizing a compensated stage of disease, hemodynamic analysis did not change. CONCLUSION: G-CSF administered for 7 days was effective in preventing the onset of ventricular remodeling induced by high-dose isoproterenol with decreased collagen deposition and chamber preservation.

Long-term use of low-dose spironolactone in spontaneously hypertensive rats: effects on left ventricular hypertrophy and stiffness.

The aim of the present study was to evaluate the effect of low-dose spironolactone initiated during the early stages of hypertension development and to assess the effects of chronic pressure overload on ventricular remodeling in rats. Male spontaneously hypertensive rats (SHRs) (4 weeks) were randomized to receive daily spironolactone (20 mg/kg) or vehicle (mineral oil) from 4 weeks to 8 months of age. Systolic blood pressure was measured non-invasively by tail-cuff pletysmography at baseline, 4 and 8 months. Hemodynamic assessment was performed at the end of treatment by arterial and ventricular catheterization. An in situ left ventricular pressure-volume curve was created to evaluate dilatation and wall stiffness. Systolic blood pressure at 1 month of age was higher in SHRs than in the Wistar group; it increased throughout the follow-up period and remained elevated with treatment (Wistar: 136 ± 2, SHR: 197 ± 6.8, SHR-Spiro: 207 ± 7.1 mmHg; p < 0.05). Spironolactone reduced cardiac hypertrophy (Wistar: 1.25 ± 0.03 SHR: 1.00 ± 0.03, SHR-Spiro: 0.86 ± 0.02 g; p < 0.05) and left ventricular mass normalized to body weight (Wistar: 2.51 ± 0.06, SHR: 2.70 ± 0.08, 2.53 ± 0.07 mg/g; p < 0.05). Moreover, the left ventricular wall stiffness that was higher in SHRs was partially reduced by spironolactone treatment (Wistar: 0.370 ± 0.032; SHR: 0.825 ± 0.058; SHR-Spiro: 0.650 ± 0.023 mmHg/ml; p < 0.05). Our results show that long-term spironolactone treatment initiated at the early stage of hypertension development reduces left ventricular hypertrophy and wall stiffness in SHRs.

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake.

OBJECTIVE: To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake. INTRODUCTION: High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system. METHODS: Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1% NaCl solution (SHR-Salt), or a 1% NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg⁻¹) (SHRSalt- S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a double-lumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressure-volume curves. RESULTS: The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar = 109 ± 2; SHR = 118 ± 2; SHR-Salt = 117 ± 2; SHR-Salt-S = 116 ± 2 mmHg; P < 0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar = 2.90 ± 0.06; SHR = 3.44 ± 0.07; SHR-Salt = 3.68 ± 0.07; SHR-Salt-S = 3.46 ± 0.05 mg/g; P < 0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar = -3698 ± 92; SHR = -3729 ± 125; SHR-Salt = -3342 ± 80; SHR-Salt-S = -3647 ± 104 mmHg/s; P < 0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar = 1.40 ± 0.04; SHR = 1.60 ± 0.05; SHR-Salt = 1.67 ± 0.12; SHR-Salt- S = 1.45 ± 0.03 mmHg/ml; P < 0.05). CONCLUSION: Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

OBJECTIVE: To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake. INTRODUCTION: High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system. METHODS: Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1 percent NaCl solution (SHR-Salt), or a 1 percent NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg-1) (SHRSalt- S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a doublelumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressurevolume curves. RESULTS: The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar = 109±2; SHR = 118±2; SHR-Salt = 117±2; SHR-Salt-S = 116±2 mmHg; P<0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar = 2.90±0.06; SHR = 3.44±0.07; SHR-Salt = 3.68±0.07; SHR-Salt-S = 3.46±0.05 mg/g; P<0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar = -3698±92; SHR = -3729±125; SHR-Salt = -3342±80; SHR-Salt-S = -3647±104 mmHg/s; P<0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar = 1.40±0.04; SHR = 1.60±0.05; SHR-Salt = 1.67±0.12; SHR-Salt- S = 1.45±0.03 mmHg/ml; P<0.05). CONCLUSION: Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.