Influence of apocynin on cardiac remodeling in rats with streptozotocin-induced diabetes mellitus.

BACKGROUND: Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats. METHODS: Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test. RESULTS: Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus.

PURPOSE: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM). METHODS: Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney. RESULTS: Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.

Low Intensity Physical Exercise Attenuates Cardiac Remodeling and Myocardial Oxidative Stress and Dysfunction in Diabetic Rats.

UNLABELLED: We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73 ± 0.49; C-Ex: 5.67 ± 0.53; DM-Sed: 6.41 ± 0.54; DM-Ex: 5.81 ± 0.50 mm; P < 0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. CONCLUSION: Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.

Diastolic function is associated with quality of life and exercise capacity in stable heart failure patients with reduced ejection fraction.

Exercise capacity and quality of life (QOL) are important outcome predictors in patients with systolic heart failure (HF), independent of left ventricular (LV) ejection fraction (LVEF). LV diastolic function has been shown to be a better predictor of aerobic exercise capacity in patients with systolic dysfunction and a New York Heart Association (NYHA) classification ≥ II. We hypothesized that the currently used index of diastolic function E/e' is associated with exercise capacity and QOL, even in optimally treated HF patients with reduced LVEF. This prospective study included 44 consecutive patients aged 55 ± 11 years (27 men and 17 women), with LVEF<0.50 and NYHA functional class I-III, receiving optimal pharmacological treatment and in a stable clinical condition, as shown by the absence of dyspnea exacerbation for at least 3 months. All patients had conventional transthoracic echocardiography and answered the Minnesota Living with HF Questionnaire, followed by the 6-min walk test (6MWT). In a multivariable model with 6MWT as the dependent variable, age and E/e' explained 27% of the walked distance in 6MWT (P=0.002; multivariate regression analysis). No association was found between walk distance and LVEF or mitral annulus systolic velocity. Only normalized left atrium volume, a sensitive index of diastolic function, was associated with decreased QOL. Despite the small number of patients included, this study offers evidence that diastolic function is associated with physical capacity and QOL and should be considered along with ejection fraction in patients with compensated systolic HF.

Diastolic function is associated with quality of life and exercise capacity in stable heart failure patients with reduced ejection fraction

Exercise capacity and quality of life (QOL) are important outcome predictors in patients with systolic heart failure (HF), independent of left ventricular (LV) ejection fraction (LVEF). LV diastolic function has been shown to be a better predictor of aerobic exercise capacity in patients with systolic dysfunction and a New York Heart Association (NYHA) classification ≥II. We hypothesized that the currently used index of diastolic function E/e' is associated with exercise capacity and QOL, even in optimally treated HF patients with reduced LVEF. This prospective study included 44 consecutive patients aged 55±11 years (27 men and 17 women), with LVEF<0.50 and NYHA functional class I-III, receiving optimal pharmacological treatment and in a stable clinical condition, as shown by the absence of dyspnea exacerbation for at least 3 months. All patients had conventional transthoracic echocardiography and answered the Minnesota Living with HF Questionnaire, followed by the 6-min walk test (6MWT). In a multivariable model with 6MWT as the dependent variable, age and E/e' explained 27% of the walked distance in 6MWT (P=0.002; multivariate regression analysis). No association was found between walk distance and LVEF or mitral annulus systolic velocity. Only normalized left atrium volume, a sensitive index of diastolic function, was associated with decreased QOL. Despite the small number of patients included, this study offers evidence that diastolic function is associated with physical capacity and QOL and should be considered along with ejection fraction in patients with compensated systolic HF.

Efeito do ultra-som e do d-pantenol na regeneracao tegumentar / Effect of ultrasound and dexpanthenol on wound healing

Estudar os efeitos dos tratamentos com ultra-som (US) e d-pantenol (d-p) na reparacao tegumentar em ratos por meio de analise histoetrica e histopatologica. Metodo: foram utilizados 50 ratos wistar, anestesiados por Thionembutal sodico (50 mg/kg), dos quais foi retirado 1cm2 de pele na rehiao dorsal, sendo que 25 foram submetidos a tratamento diario por 7 dias e 25 por 14 dias. Os grupos experimentais (n=5) foram: controle (C), gel (G), US (3MHz, 0,1 W/cm2, 1 minuto, modo continuo), d-p na concentracao de (10 por cento) e US+d-p. seccoes de 6 um de espessura da lesao foram procesados para coloracao em Hematoxilina-Eosina. A re-epitelizacao e o numero de fibroblastos e leucocitos foram obtidos num processador de imagens (Software Imagem Pro-Plus) e analisados pelo teste ANOVA, seguido de Tukey para comparacao da medias. Resultados: a re-epitelizacao dos grupos US(1869,6+-238,4 um) e US+d-p(2167,7+-232 um) foi maior (p<-0,05) em relacao ao C(987,7+-146,8 um), mas nao diferiram entre si. O numero de fibroblastos no grupo US (419+-37) com sete dias de tratamento foi significativamente maior em relacao aos demais grupos: (C:250+-17), (d-p:296+-49) e (US+d-p:274+-18). No grupo US, tratado por sete dias, a media de leucocitos (134+-15) foi menor (p<-0,05) em relacao ao C (253+-37), d-p (222+-29) e US+d-p (153+-14), evidenciando seu efeito na fase inicial do processo inflamatorio. Conclusoes: o US acelera o processo de reparo, bem como associado ao d-p. Porem, essa associacao dos tratamentos, US+d-p, n'ao mostrou resultados significativos em relacao ao tratamento com US isolado