Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina / Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin

Resumo Fundamento: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. Objetivos: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. Métodos: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. Resultados: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. Conclusão: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

Abstract Background: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. Objective: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. Methods: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. Results: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. Conclusion: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

Influence of Consumption of Orange Juice (Citrus Sinensis) on Cardiac Remodeling of Rats Submitted to Myocardial Infarction. / Influência do Consumo de Suco de Laranja (Citrus Sinensis) na Remodelação Cardíaca de Ratos Submetidos a Infarto do Miocárdio.

BACKGROUND: Orange juice (OJ) is rich in polyphenols with anti-inflammatory and antioxidant properties. After myocardial infarction (MI), complex changes occur in cardiac structure and function, which is known as cardiac remodeling (CR). Oxidative stress and inflammation can modulate this process. We hypothesized that the consumption of OJ attenuates the CR after MI. OBJECTIVES: To evaluate the influence of OJ on CR after MI by analysis of functional, morphological, oxidative stress, inflammation, and energy metabolism variables. METHODS: A total of 242 male rats weighing 200-250 g were submitted to a surgical procedure (coronary artery ligation or simulated surgery). Seven days after surgery, survivors were assigned to one of the four groups 1) SM, sham animals with water and maltodextrin (n= 20); 2) SOJ, sham animals with OJ (n= 20); 3) IM, infarcted animals with water and maltodextrin (n= 40); and 4) IOJ, infarcted animals with OJ (n = 40). Statistical analysis was performed by the two-way ANOVA supplemented by Holm-Sidak. Results are presented as mean ± standard deviation, the level of significance adopted was 5%. RESULTS: After 3 months, MI led to left ventricular (LV) hypertrophy, with systolic and diastolic dysfunction, and increased oxidative stress and inflammatory mediators. OJ intake reduced LV cavity and improved systolic and diastolic function. The OJ animals presented lower activity of glutathione peroxidase and higher expression of heme-oxygenase-1 (HO-1). CONCLUSION: OJ attenuated CR in infarcted rats and HO-1 may be play an important role in this process.

FUNDAMENTO: O suco de laranja (SL) é rico em polifenóis com propriedades anti-inflamatórias e antioxidantes. Após o infarto do miocárdio (IM), mudanças complexas ocorrem na estrutura e na função cardíacas, processo conhecido como remodelação cardíaca (RC). O estresse oxidativo e a inflamação podem modular esse processo. Nossa hipótese foi a de que o consumo de SL atenua a RC após o IM. OBJETIVOS: Avaliar a influência do SL sobre a RC após IM pela análise de variáveis funcionais, morfológicas, de estresse oxidativo, de inflação, e de metabolismo energético. MÉTODOS: Um total de 242 ratos machos pesando entre 200 e 250g foram submetidos a um procedimento cirúrgico (ligação da artéria coronária ou cirurgia simulada). Sete dia após a cirurgia, os animais sobreviventes foram divididos para um dos quatro grupos: 1) SM, animais sham que receberam água e maltodextrina (n= 20); 2) SSL, animais sham que receberam SL (n= 20); 3) IM, animais infartados que receberam água e maltodextrina (n= 40); e 4) ISL, animais infartados que receberam SL (n = 40). A análise estatística foi realizada pelo teste de ANOVA com dois fatores com o teste de Holm-Sidak. Os resultados foram apresentados em média ± desvio padrão, e o nível de significância adotado foi de 5%. RESULTADOS: Três meses depois, o IM levou à hipertrofia do ventrículo esquerdo (VE), com disfunção sistólica e diastólica, e aumento nos mediadores inflamatórios e de estresse oxidativo. Os animais que consumiram SL apresentaram menor atividade da glutationa peroxidase e maior expressão da heme-oxigenase-1 (HO-1). CONCLUSÃO: O SL atenuou a RC, e a HO-1 pode exercer um importante papel nesse processo.

Influência do Consumo de Suco de Laranja (Citrus Sinensis) na Remodelação Cardíaca de Ratos Submetidos a Infarto do Miocárdio / Influence of Consumption of Orange Juice (Citrus Sinensis) on Cardiac Remodeling of Rats Submitted to Myocardial Infarction

Resumo Fundamento O suco de laranja (SL) é rico em polifenóis com propriedades anti-inflamatórias e antioxidantes. Após o infarto do miocárdio (IM), mudanças complexas ocorrem na estrutura e na função cardíacas, processo conhecido como remodelação cardíaca (RC). O estresse oxidativo e a inflamação podem modular esse processo. Nossa hipótese foi a de que o consumo de SL atenua a RC após o IM. Objetivos Avaliar a influência do SL sobre a RC após IM pela análise de variáveis funcionais, morfológicas, de estresse oxidativo, de inflação, e de metabolismo energético. Métodos Um total de 242 ratos machos pesando entre 200 e 250g foram submetidos a um procedimento cirúrgico (ligação da artéria coronária ou cirurgia simulada). Sete dia após a cirurgia, os animais sobreviventes foram divididos para um dos quatro grupos: 1) SM, animais sham que receberam água e maltodextrina (n= 20); 2) SSL, animais sham que receberam SL (n= 20); 3) IM, animais infartados que receberam água e maltodextrina (n= 40); e 4) ISL, animais infartados que receberam SL (n = 40). A análise estatística foi realizada pelo teste de ANOVA com dois fatores com o teste de Holm-Sidak. Os resultados foram apresentados em média ± desvio padrão, e o nível de significância adotado foi de 5%. Resultados Três meses depois, o IM levou à hipertrofia do ventrículo esquerdo (VE), com disfunção sistólica e diastólica, e aumento nos mediadores inflamatórios e de estresse oxidativo. Os animais que consumiram SL apresentaram menor atividade da glutationa peroxidase e maior expressão da heme-oxigenase-1 (HO-1). Conclusão O SL atenuou a RC, e a HO-1 pode exercer um importante papel nesse processo.

Abstract Background Orange juice (OJ) is rich in polyphenols with anti-inflammatory and antioxidant properties. After myocardial infarction (MI), complex changes occur in cardiac structure and function, which is known as cardiac remodeling (CR). Oxidative stress and inflammation can modulate this process. We hypothesized that the consumption of OJ attenuates the CR after MI. Objectives To evaluate the influence of OJ on CR after MI by analysis of functional, morphological, oxidative stress, inflammation, and energy metabolism variables. Methods A total of 242 male rats weighing 200-250 g were submitted to a surgical procedure (coronary artery ligation or simulated surgery). Seven days after surgery, survivors were assigned to one of the four groups 1) SM, sham animals with water and maltodextrin (n= 20); 2) SOJ, sham animals with OJ (n= 20); 3) IM, infarcted animals with water and maltodextrin (n= 40); and 4) IOJ, infarcted animals with OJ (n = 40). Statistical analysis was performed by the two-way ANOVA supplemented by Holm-Sidak. Results are presented as mean ± standard deviation, the level of significance adopted was 5%. Results After 3 months, MI led to left ventricular (LV) hypertrophy, with systolic and diastolic dysfunction, and increased oxidative stress and inflammatory mediators. OJ intake reduced LV cavity and improved systolic and diastolic function. The OJ animals presented lower activity of glutathione peroxidase and higher expression of heme-oxygenase-1 (HO-1). Conclusion OJ attenuated CR in infarcted rats and HO-1 may be play an important role in this process.

Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin. / Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina.

BACKGROUND: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. OBJECTIVE: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. METHODS: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. RESULTS: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid ß-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. CONCLUSION: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

FUNDAMENTO: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. OBJETIVOS: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. MÉTODOS: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. RESULTADOS: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na ß-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. CONCLUSÃO: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

Pamidronate attenuates diastolic dysfunction induced by myocardial infarction associated with changes in geometric patterning.

BACKGROUND/AIMS: The aim of this study was to evaluate the influence of pamidronate on ventricular remodeling after myocardial infarction. METHODS: Male Wistar rats were assigned to four groups: a sham group, in which animals were submitted to simulated surgery and received weekly subcutaneous injection of saline (S group; n=14); a group in which animals received weekly subcutaneous injection of pamidronate (3 mg/kg of body weight) and were submitted to simulated surgery (SP group, n=14); a myocardial infarction group, in which animals were submitted to coronary artery ligation and received weekly subcutaneous injection of saline (MI group, n=13); and a myocardial infarction group with pamidronate treatment (MIP group, n=14). The rats were observed for three months. RESULTS: Animals submitted to MI had left chamber enlargement and worse diastolic and systolic function compared with SHAM groups. E/A ratio, LV posterior and relative wall thickness were lower in the MIP compared with the MI group. There was no interaction between pamidronate administration and MI on systolic function, myocyte hypertrophy, collagen content, and calcium handling proteins. CONCLUSION: Pamidronate attenuates diastolic dysfunction following MI.

The role of lipotoxicity in smoke cardiomyopathy.

BACKGROUND/AIMS: Experimental and clinical studies have shown the direct toxic effects of cigarette smoke (CS) on the myocardium, independent of vascular effects. However, the underlying mechanisms are not well known. METHODS: Wistar rats were allocated to control (C) and cigarette smoke (CS) groups. CS rats were exposed to cigarette smoke for 2 months. RESULTS: After that morphometric, functional and biochemical parameters were measured. The echocardiographic study showed enlargement of the left atria, increase in the left ventricular systolic volume and reduced systolic function. Within the cardiac metabolism, exposure to CS decreased beta hydroxy acyl coenzyme A dehydrogenases and citrate synthases and increased lactate dehydrogenases. Peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were expressed similarly in both groups. CS increased serum lipids and myocardial triacylglycerols (TGs). These data suggest that impairment in fatty acid oxidation and the accumulation of cardiac lipids characterize lipotoxicity. CS group exhibited increased oxidative stress and decreased antioxidant defense. Finally, the myocyte cross-sectional area and active Caspase 3 were increased in the CS group. CONCLUSION: The cardiac remodeling that was observed in the CS exposure model may be explained by abnormalities in energy metabolism, including lipotoxicity and oxidative stress.

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction.

OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats.

Mechanisms involved in the beneficial effects of spironolactone after myocardial infarction.

INTRODUCTION: Our objective was to analyze the effect of spironolactone on cardiac remodeling after experimental myocardial infarction (MI), assessed by matricellular proteins levels, cardiac collagen amount and distribution, myocardial tissue metalloproteinase inhibitor-1 (TIMP-1) concentration, myocyte hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac function. METHODS: Wistar rats were assigned to 4 groups: control group, in which animals were submitted to simulated surgery (SHAM group; n=9); group that received spironolactone and in which animals were submitted to simulated surgery (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and myocardial infarction group with spironolactone supplementation (MI-S group, n=15). The rats were observed for 3 months. RESULTS: The MI group had higher values of left cardiac chambers and mass index and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in the MI groups. However, spironolactone did not influence any of these variables. The MI-S group had a lower myocardial hydroxyproline concentration and myocyte cross-sectional area compared with the MI group. Myocardial periostin and collagen type III were lower in the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group. CONCLUSIONS: The predominant consequence of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of other remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels.

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction

OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats. .

Serum metalloproteinases 2 and 9 as predictors of gait status, pressure ulcer and mortality after hip fracture.

INTRODUCTION: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. METHODS: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. RESULTS: Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. CONCLUSIONS: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture.

Mini Nutritional Assessment predicts gait status and mortality 6 months after hip fracture.

The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.

Aldosterone is not involved in the ventricular remodeling process induced by tobacco smoke exposure.

BACKGROUND/AIMS: Renin-angiotensin-aldosterone system blockade with a mineralocorticoid-receptor antagonist has not yet been studied in exposure to tobacco smoke (TS) models. Thus, this study investigated the role of spironolactone on cardiac remodeling induced by exposure to tobacco smoke. METHODS: Male Wistar rats were divided into 4 groups: a control group (group C, n=11); a group with 2 months of cigarette smoke exposure (group TS-C, n=13); a group that received spironolactone 20 mg/kg of diet/day and no cigarette smoke exposure (group TS-S, n=13); and a group with 2 months of cigarette smoke exposure and spironolactone supplementation (group S, n=12). The rats were observed for a period of 60 days, during which morphological, biochemical and functional analyses were performed. RESULTS: There was no difference in invasive mean arterial pressure among the groups. There were no interactions between tobacco smoke exposure and spironolactone in the morphological and functional analysis. However, in the echocardiographic analysis, the TS groups had left chamber enlargement, higher left ventricular mass index and higher isovolumetric relaxation time corrected by heart rate compared with the non-TS groups. In vitro left ventricular diastolic function also worsened in the TS groups and was not influenced by spironolactone. In addition, there were no differences in myocardial levels of IFN-γ, TNF-α, IL-10, ICAM-1 and GLUT4 [TS: OR 0.52, 95%CI (-0.007; 0.11); Spironolactone: OR -0.01, 95%CI (-0.07;0.05)]. CONCLUSION: Our data do not support the participation of aldosterone in the ventricular remodeling process induced by exposed to cigarette smoke.

Handgrip strength predicts pressure ulcers in patients with hip fractures.

OBJECTIVE: Pressure ulcer (PU) is a frequent complication of hip fracture. Studies were carried out to identify the risk factors of PU development after hip fractures. The objective of the study was to determine the role of anthropometric measurements and handgrip strength as predictors of PUs in patients with hip fractures during their hospital stay and 30 d after discharge, which has not yet been established. METHODS: Ninety-two consecutive patients with hip fractures who were older than 65 y old and admitted to an orthopedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, anthropometric measurements were taken (circumferences of the arm, waist, thigh, calf, triceps, and biceps and subscapular and suprailiac skinfolds), handgrip strength was measured, and blood samples were collected. PU evaluations were performed during the hospital stay and 30 d after hospital discharge. RESULTS: Three patients were excluded because of PUs before hospitalization. Eighty-nine patients (average age 80.6 ± 7.5 y) were studied; 70.8% were women, and 49.4% developed PUs during their hospital stay. In a univariate analysis, length of hospital stay (P = 0.001) and handgrip strength (P = 0.02), but not body circumferences and skinfolds, were associated with PUs during a hospital stay. Only handgrip strength (P = 0.007) was associated with PUs 30 d after hospital discharge. In a multivariate analysis, only handgrip strength was found to predict PU development at these points. CONCLUSION: Handgrip strength was found to predict PU development in patients with hip fractures during their hospital stay and 30 d after discharge.

Tobacco smoke induces ventricular remodeling associated with an increase in NADPH oxidase activity.

BACKGROUND: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. METHODS: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. RESULTS: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-γ, TNF-α and IL-10 were not different between the groups. CONCLUSION: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke.

Retinoic acid prevents ventricular remodelling induced by tobacco smoke exposure in rats.

OBJECTIVE: Our objective was to test the hypothesis that retinoic acid supplementation could attenuate ventricular remodelling induced by tobacco smoke exposure in rats. METHODS AND RESULTS: Wistar rats were allocated into three groups: control (C, n = 8); exposed to tobacco smoke (ETS, n = 9); exposed to tobacco smoke and all-trans-retinoic acid (ETS-RA, n = 9). After two months, cardiac function and geometry were assessed by echocardiography, and geometry changes were confirmed by morphometric analysis. Data are expressed as mean +/- SD or medians (including the lower quartile and upper quartile). ETS showed higher normalized left ventricular diastolic diameters than groups C and ETS-RA (C = 18.4 +/- 3.57 mm/kg, ETS = 23.0 +/- 1.8, ETS-RA = 19.5 +/- 0.99; P <0.05) and systolic diameters (C = 8.25 +/- 2.16 mm/kg, ETS = 11.5 +/- 1.31, ETS-RA = 8.25 +/- 0.71 mm/kg; P < 0.05). ETS showed reduced ejection fraction (C= 91 +/- 2.0, ETS = 87 +/- 3.0, ETS-RA = 92 +/- 3.0; P < 0.05) and fractional shortening (C = 55.8 +/- 4.41%, ETS = 49.7 +/- 4.43%, ETS-RA = 57.6 +/- 5.15 %; P= 0.01) compared to C and ETS-RA. ETS had increased myocyte cross-sectional area (C = 294 +/- 21 mm2, ETS = 352 +/-44, ETS-RA = 310 +/- 35; P < 0.05) compared to C and ETS-RA. Considering all variables, there were no differences between groups C and ETS-RA. CONCLUSION: Retinoic acid prevented ventricular remodelling induced by tobacco smoke exposure.