Effects of aerobic and resistance exercise on cardiac remodelling and skeletal muscle oxidative stress of infarcted rats.

We compared the influence of aerobic and resistance exercise on cardiac remodelling, physical capacity and skeletal muscle oxidative stress in rats with MI-induced heart failure. Three months after MI induction, Wistar rats were divided into four groups: Sham; sedentary MI (S-MI); aerobic exercised MI (A-MI); and resistance exercised MI (R-MI). Exercised rats trained three times a week for 12 weeks on a treadmill or ladder. Statistical analysis was performed by ANOVA or Kruskal-Wallis test. Functional aerobic capacity was greater in A-MI and strength gain higher in R-MI. Echocardiographic parameters did not differ between infarct groups. Reactive oxygen species production, evaluated by fluorescence, was higher in S-MI than Sham, and lipid hydroperoxide concentration was lower in A-MI than the other groups. Glutathione peroxidase activity was higher in A-MI than S-MI and R-MI. Superoxide dismutase was lower in S-MI than Sham and R-MI. Gastrocnemius cross-sectional area, satellite cell activation and expression of the ubiquitin-proteasome system proteins did not differ between groups. In conclusion, aerobic exercise and resistance exercise improve functional capacity and maximum load carrying, respectively, without changing cardiac remodelling in infarcted rats. In the gastrocnemius, infarction increases oxidative stress and changes antioxidant enzyme activities. Aerobic exercise reduces oxidative stress and attenuates superoxide dismutase and glutathione peroxidase changes.

Exercise during transition from compensated left ventricular hypertrophy to heart failure in aortic stenosis rats.

We evaluated the influence of aerobic exercise on cardiac remodelling during the transition from compensated left ventricular (LV) hypertrophy to clinical heart failure in aortic stenosis (AS) rats. Eighteen weeks after AS induction, rats were assigned into sedentary (AS) and exercised (AS-Ex) groups. Results were compared to Sham rats. Exercise was performed on treadmill for 8 weeks. Exercise improved functional capacity. Echocardiogram showed no differences between AS-Ex and AS groups. After exercise, fractional shortening and ejection fraction were lower in AS-Ex than Sham. Myocyte diameter and interstitial collagen fraction were higher in AS and AS-Ex than Sham; however, myocyte diameter was higher in AS-Ex than AS. Myocardial oxidative stress, evaluated by lipid hydroperoxide concentration, was higher in AS than Sham and was normalized by exercise. Gene expression of the NADPH oxidase subunits NOX2 and NOX4, which participate in ROS generation, did not differ between groups. Activity of the antioxidant enzyme superoxide dismutase was lower in AS and AS-Ex than Sham and glutathione peroxidase was lower in AS-Ex than Sham. Total and reduced myocardial glutathione, which is involved in cellular defence against oxidative stress, was lower in AS than Sham and total glutathione was higher in AS-Ex than AS. The MAPK JNK was higher in AS-Ex than Sham and AS groups. Phosphorylated P38 was lower in AS-Ex than AS. Despite improving functional capacity, aerobic exercise does not change LV function in AS rats. Exercise restores myocardial glutathione, reduces oxidative stress, impairs JNK signalling and further induces myocyte hypertrophy.

N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats During Transition from Compensated Left Ventricular Hypertrophy to Heart Failure.

BACKGROUND/AIMS: To evaluate the effects of the antioxidant N-acetylcysteine (NAC) on cardiac structure and function in rats with long-term ascending aortic stenosis (AS). METHODS: Four months after inducing AS, Wistar rats were assigned into the groups Sham, AS, and AS treated with NAC (AS-NAC) and followed for eight weeks. Cardiac structure and function were evaluated by echocardiogram. Myocardial antioxidant enzymes activity was measured by spectrophotometry and malondialdehyde serum concentration by HPLC. Gene expression of NADPH oxidase subunits NOX2, NOX4, p22 phox, and p47 phox was assessed by real time RT-PCR and protein expression of MAPK proteins by Western blot. Statistical analyzes were performed with Goodman and ANOVA or Mann-Whitney Results: NAC restored myocardial total glutathione (Sham 20.8±3.00; AS 12.6±2.92; AS-NAC 17.6±2.45 nmol/g tissue; p<0.05 AS vs Sham and AS-NAC). Malondialdehyde serum concentration was lower in AS-NAC and myocardial lipid hydroperoxide was higher in AS (Sham 199±48.1; AS 301±36.0; AS-NAC 181±41.3 nmol/g tissue). Glutathione peroxidase activity was lower in AS than Sham. Echocardiogram showed LV concentric hypertrophy with systolic and diastolic dysfunction before and after treatment; no differences were observed between AS-NAC and AS groups. NAC reduced p-ERK and p-JNK protein expression, attenuated myocardial fibrosis, and decreased the frequency of right ventricular hypertrophy. CONCLUSION: N-acetylcysteine restores myocardial total glutathione, reduces systemic and myocardial oxidative stress, improves MAPK signaling, and attenuates myocardial fibrosis in aortic stenosis rats.

Modulation of MAPK and NF-954;B Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats.

BACKGROUND/AIMS: Although increased oxidative stress plays a role in heart failure (HF)-induced skeletal myopathy, signaling pathways involved in muscle changes and the role of antioxidant agents have been poorly addressed. We evaluated the effects of N-acetylcysteine (NAC) on intracellular signaling pathways potentially modulated by oxidative stress in soleus muscle from HF rats. METHODS AND RESULTS: Four months after surgery, rats were assigned to Sham, myocardial infarction (MI)-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. Oxidative stress was evaluated in serum and soleus muscle; malondialdehyde was higher in MI-C than Sham and did not differ between MI-C and MI-NAC. Oxidized glutathione concentration in soleus muscle was similar in Sham and MI-C, and lower in MI-NAC than MI-C (Sham 0.168 ± 0.056; MI-C 0.223 ± 0.073; MI-NAC 0.136 ± 0.023 nmol/mg tissue; p = 0.014). Western blot showed increased p-JNK and decreased p38, ERK1/2, and p-ERK1/2 in infarcted rats. NAC restored ERK1/2. NF-954;B p65 subunit was reduced; p-Ser276 in p65 and I954;B was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-954;B p65 subunit, but decreased p-Ser276 and p-Ser536. CONCLUSION: N-acetylcysteine modulates MAPK and NF-954;B signaling pathways in soleus muscle of HF rats.

Long-term low intensity physical exercise attenuates heart failure development in aging spontaneously hypertensive rats.

BACKGROUND: Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF) development and cardiac remodeling in aging spontaneously hypertensive rats (SHR). METHODS: Sixteen month old SHR (n=50) and normotensive Wistar-Kyoto (WKY, n=35) rats were divided into sedentary (SED) and exercised (EX) groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. STATISTICAL ANALYSES: ANOVA and Tukey or Mann-Whitney, and Goodman test. RESULTS: Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV) systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. CONCLUSION: Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

Influence of N- acetylcysteine on oxidative stress in slow-twitch soleus muscle of heart failure rats.

BACKGROUND: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. METHODS AND RESULTS: Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47(phox) was lower in MI-C than Sham. NAC decreased NOX4 and p22(phox) expression. CONCLUSIONS: We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.

Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats.

BACKGROUND: We evaluated the role of the aldosterone blocker spironolactone in attenuating long-term pressure overload-induced cardiac remodeling and heart failure (HF) in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Thirteen month-old male SHR were assigned to control (SHR-C, n=20) or spironolactone (SHR-SPR, 20 mg/kg/day, n=24) groups for six months. Normotensive Wistar-Kyoto rats (WKY, n=15) were used as controls. Systolic blood pressure was higher in SHR groups and unchanged by spironolactone. Right ventricular hypertrophy, which characterizes HF in SHR, was less frequent in SHR-SPR than SHR-C. Echocardiographic parameters did not differ between SHR groups. Myocardial function was improved in SHR-SPR compared to SHR-C [developed tension: WKY 4.85±0.68; SHR-C 5.22±1.64; SHR-SPR 6.80±1.49 g/mm2; -dT/dt: WKY 18.0 (16.0­19.0); SHR-C 20.8 (18.4­25.1); SHR-SPR 28.9 (24.2­34.6) g/mm2/s]. Cardiomyocyte cross-sectional area and total collagen concentration (WKY 1.06±0.34; SHR-C 1.85±0.63; SHR-SPR 1.28±0.39 µg/mg wet tissue) were greater in SHR-C than WKY and SHR-SPR. Type 3 collagen expression was lower in SHR-C than WKY and unchanged by spironolactone. Soluble collagen, type I collagen, and lysyl oxidase did not differ between groups. CONCLUSION: Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats.

Aldosterone blockade reduces mortality without changing cardiac remodeling in spontaneously hypertensive rats.

BACKGROUND: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR). METHODS: Sixteen-month-old SHR received no treatment (SHR-C, n=72) or spironolactone (SHR-SPR, 20 mg/kg/day, n=34) for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. STATISTICS: Student's t test; Log rank test (Kaplan Meyer). RESULTS: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004). Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg). Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and ß-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. CONCLUSION: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.

Extensive impact of saturated fatty acids on metabolic and cardiovascular profile in rats with diet-induced obesity: a canonical analysis.

BACKGROUND: Although hypercaloric interventions are associated with nutritional, endocrine, metabolic, and cardiovascular disorders in obesity experiments, a rational distinction between the effects of excess adiposity and the individual roles of dietary macronutrients in relation to these disturbances has not previously been studied. This investigation analyzed the correlation between ingested macronutrients (including sucrose and saturated and unsaturated fatty acids) plus body adiposity and metabolic, hormonal, and cardiovascular effects in rats with diet-induced obesity. METHODS: Normotensive Wistar-Kyoto rats were submitted to Control (CD; 3.2 Kcal/g) and Hypercaloric (HD; 4.6 Kcal/g) diets for 20 weeks followed by nutritional evaluation involving body weight and adiposity measurement. Metabolic and hormonal parameters included glycemia, insulin, insulin resistance, and leptin. Cardiovascular analysis included systolic blood pressure profile, echocardiography, morphometric study of myocardial morphology, and myosin heavy chain (MHC) protein expression. Canonical correlation analysis was used to evaluate the relationships between dietary macronutrients plus adiposity and metabolic, hormonal, and cardiovascular parameters. RESULTS: Although final group body weights did not differ, HD presented higher adiposity than CD. Diet induced hyperglycemia while insulin and leptin levels remained unchanged. In a cardiovascular context, systolic blood pressure increased with time only in HD. Additionally, in vivo echocardiography revealed cardiac hypertrophy and improved systolic performance in HD compared to CD; and while cardiomyocyte size was unchanged by diet, nuclear volume and collagen interstitial fraction both increased in HD. Also HD exhibited higher relative ß-MHC content and ß/α-MHC ratio than their Control counterparts. Importantly, body adiposity was weakly associated with cardiovascular effects, as saturated fatty acid intake was directly associated with most cardiac remodeling measurements while unsaturated lipid consumption was inversely correlated with these effects. CONCLUSION: Hypercaloric diet was associated with glycemic metabolism and systolic blood pressure disorders and cardiac remodeling. These effects directly and inversely correlated with saturated and unsaturated lipid consumption, respectively.

Efficacy of Different Cold-Water Immersion Temperatures on Neuromotor Performance in Young Athletes.

Cold-Water-Immersion (CWI) has been frequently used to accelerate muscle recovery and to improve performance after fatigue onset. In the present study, the aim was to investigate the effects of different CWI temperatures on neuromuscular activity on quadriceps after acute fatigue protocol. Thirty-six young athletes (16.9 ± 1.4 years-old; 72.1 ± 13.8 kg; 178.4 ± 7.2 cm) were divided into three groups: passive recovery group (PRG); CWI at 5 °C group (5G); and CWI at 10 °C group (10G). All participants performed a fatigue exercise protocol; afterwards, PRG performed a passive recovery (rest), while 5G and 10G were submitted to CWI by means of 5 °C and 10 °C temperatures during 10 min, respectively. Fatigue protocol was performed by knee extension at 40% of isometric peak force from maximal isometric voluntary contraction. Electromyography was used to evaluate neuromuscular performance. The passive recovery and CWI at 5 °C were associated with normalized isometric force and quadriceps activation amplitude from 15 until 120 min after exercise-induced fatigue (F = 7.169, p < 0.001). CWI at 5 °C and 10 °C showed higher muscle activation (F = 6.850, p < 0.001) and lower median frequency (MF) than passive recovery after 15 and 30 min of fatigue (F = 5.386, p < 0.001). For neuromuscular efficiency (NME) recovery, while PRG normalized NME values after 15 min, 5G and 10G exhibited these responses after 60 and 30 min (F = 4.330, p < 0.01), respectively. Passive recovery and CWI at 5 °C and 10 °C revealed similar effects in terms of recovery of muscle strength and NME, but ice interventions resulted in higher quadriceps activation recovery.

Influence of high-intensity interval training and intermittent fasting on myocardium apoptosis pathway and cardiac morphology of healthy rats.

AIM: To evaluate the influence of intermittent fasting and high-intensity interval training (HIIT) on myocardial apoptosis signaling and cardiac morphological characteristics in healthy rats. METHODS: Male Wistar rats (n = 60) were divided into four groups: sedentary control (SED-C), intermittent fasting (SED-IF), high-intensity interval training (HIIT-C), and high-intensity interval training plus intermittent fasting (HIIT-IF). SED-C and HIIT-C groups were treated daily with ad libitum chow; SED-IF and HIIT-IF received the same standard chow every other day. HIIT-C and HIIT-IF rats were submitted to an HIIT protocol five times a week for 12 weeks. At the end of the experiment, functional capacity, cardiac morphology, and expression of apoptosis signaling pathways-related proteins were analyzed. KEY FINDINGS: HIIT increased cardiomyocyte cross-sectional area, collagen interstitial fraction, and the pro-apoptotic proteins AIF and caspase-3 expression, and reduced pro-apoptotic protein CYTC expression and the cleaved-to-non-cleaved PARP-1 ratio in myocardium. Intermittent fasting reduced cardiomyocyte cross-sectional area, collagen interstitial fraction, and expression of Bax, CYTC and cleaved PARP-1, and increased expression of the anti-apoptotic protein BCL-2. SMAC, ARC, and caspase-8 expression was not changed by HIIT or intermittent fasting. SIGNIFICANCE: HIIT promotes cardiomyocyte hypertrophy and interstitial fibrosis, and modulates the apoptosis signaling pathway in healthy rat myocardium. Intermittent fasting reduces pro-apoptotic and increases antiapoptotic signaling, besides attenuating HIIT-induced cardiomyocyte hypertrophy and myocardial interstitial fibrosis.

Effects of Circuit Weight-Interval Training on Physical Fitness, Cardiac Autonomic Control, and Quality of Life in Sedentary Workers.

Sedentary behaviors, those that involve sitting and low levels of energy expenditure, have been associated with several adverse cardiometabolic effects. This study evaluated the chronic effects of a combined circuit weight interval training (CWIT) on physical fitness, quality of life, and heart rate variability (HRV), and compared the effects of CWIT-induced autonomic adaptations on different postures in adult sedentary workers. Twenty-seven sedentary workers (age 36.9 ± 9.2 years old, 13 men and 14 women) were divided into two groups: control, who continued their sedentary behavior, and experimental, who were submitted to a CWIT for 12 weeks, completing two ~40 min sessions per week. Monitoring of 8th, 16th, and 24th sessions revealed a moderate training load during sessions. Participants exhibited an improved aerobic capacity (VO2max, 34.03 ± 5.36 vs. 36.45 ± 6.05 mL/kg/min, p < 0.05) and flexibility (22.6 ± 11.4 vs. 25.3 ± 10.1 cm, p < 0.05) after the training period. In addition, they showed greater quality of life scores. However, the CWIT did not change body composition. Interestingly, more HRV parameters were improved in the seated position. The CWIT used in the current study was associated with improvements in several fitness and quality of life parameters, as well as in cardiac autonomic control of HR in adult sedentary workers. Examination of different body positions when evaluating changes in HRV appears to be a relevant aspect to be considered in further studies. Future randomized controlled trials (RCTs) with larger samples of both sexes should confirm these promising results.

Tissue vitamin A insufficiency results in adverse ventricular remodeling after experimental myocardial infarction.

BACKGROUND/AIMS: The role of tissue vitamin-A insufficiency on post-infarction ventricular remodeling is unknown. We tested the hypothesis that cardiac vitamin A insufficiency on post-infarction is associated with adverse myocardial remodeling. METHODS: After infarction, rats were allocated into two groups: C (controls, n=25); VA (dietary vitamin A restriction, n= 26). After 3 months, the animals were submitted to echocardiogram, morphometric and biochemical analysis. RESULTS: Rats fed the vitamin-A-deficient diet had lower heart and liver retinol concentration and normal plasma retinol. There were no differences in infarct size between the groups. VA showed higher diastolic left ventricular area normalised by body weight (C= 1.81 ± 0.4 cm2/kg, VA= 2.15 ± 0.3 cm2/kg; p=0.03), left ventricular diameter (C= 9.4 ± 1.4 mm, VA= 10.5 ± 1.2 mm; p=0.04), but similar systolic ventricular fractional area change (C= 33.0 ± 10.0 %, VA= 32.1 ± 8.7 %; p=0.82). VA showed decreased isovolumetric relaxation time normalised by heart rate (C= 68.8 ± 11.4 ms, VA= 56.3 ± 16.8 ms; p=0.04). VA showed higher interstitial collagen fraction (C= 2.8 ± 0.9 %, VA= 3.7 ± 1.1 %; p=0.05). There were no differences in myosin heavy chain expression, metalloproteinase 2 and 9 activation, or IFN-γ and TNF-α cardiac levels. CONCLUSION: Local tissue vitamin A insufficiency intensified ventricular remodeling after MI, worsening diastolic dysfunction.

Diet-induced obesity causes metabolic, endocrine and cardiac alterations in spontaneously hypertensive rats.

BACKGROUND: Although obesity has been associated with several effects in rodents, few investigations have evaluated the metabolic, endocrine, and cardiac parameters of spontaneously hypertensive rats (SHR) with dietary-induced obesity. The current study analyzed the influence of dietary-induced obesity on metabolic, endocrine, and cardiac characteristics in SHR. MATERIAL/METHODS: Male SHR were distributed in 2 groups: C-SHR (n=10) and OB-SHR (n=10). While C-SHR received a standard commercial diet (CD; 3.2 kcal/g), OB-SHR were submitted to a hypercaloric diet (HD; 4.6 kcal/g) for 20 weeks. Nutritional, metabolic, and endocrine evaluation involved measurement of calorie intake, dietary efficiency, body weight, adiposity, glycemia, triacylglycerol, insulin, and leptin. Cardiovascular evaluation integrated systolic blood pressure (SBP), echocardiography, gross and ultrastructural morphology, and myosin heavy chain (MHC) analyses of the myocardium. RESULTS: Animals in OB-SHR had greater values of BW, adiposity, triacylglycerol, and leptin and impaired glycemic tolerance compared with the C-SHR group. In the cardiovascular context, dietary-induced obesity increased interstitial collagen, the cardiomyocyte area, and the relative expression of beta-MHC, and well as beta-/alpha-isoform ratio of MHC. Likewise, OB-SHR showed ultrastructural morphologic alterations, with loss and disorganization of myofilaments, lipid droplets, severe mitochondrial damage, and T-tubule dilation. Concerning the in-vivo cardiovascular profile, although SBP and systolic function were unchanged by dietary-induced obesity, echocardiography results evidenced impaired diastolic function in OB-SHR in relation to their control counterparts. CONCLUSIONS: Diet-induced obesity was associated with endocrine alterations, and it accentuated cardiac remodeling, promoting diastolic dysfunction of restrictive filling pattern in the SHR strain.

Chronic heart failure-induced skeletal muscle atrophy, necrosis, and changes in myogenic regulatory factors.

BACKGROUND: Although intrinsic skeletal muscle abnormalities can influence exercise intolerance during heart failure (HF), the factors responsible for muscle changes have not been elucidated. In this study we evaluated the expression of myogenic regulatory factors (MRF), myosin heavy chain (MyHC) isoforms, and fiber trophism in the soleus muscle of rats with myocardial infarction-induced heart failure. METHOD/RESULTS: Six months after surgery, 2 groups of rats were studied: sham, and infarcted rats with HF (MI/HF+, MI size: 41.1±6.3% of total left ventricular area). In the infarcted group, microscopic evaluation revealed scattered foci of fiber necrosis in combination with inflammatory cells, phagocytosis, and increased fibrous tissue. The frequency of necrotic fibers was significantly higher in the MI/HF+ group than in the sham. The MI/HF+ group had atrophy of type I, IC/IIC, and IIA fibers compared to the sham group (P<0.05). MyoD gene expression was higher in the MI/HF+ group (sham: 1.00±0.49; MI/HF+: 2.53±0.71 arbitrary units; P<0.001). Myogenin and MRF4 gene expression was similar in both groups. Myogenin protein levels were reduced in the MI/HF+ group (sham: 1.00±0.21; MI/HF+: 0.74±0.21 arbitrary units; P=0.026). MyoD and MRF4 protein levels, as well as the MyHC distribution, were not different between groups. The MI/HF+ group had higher TNF-α and IL-6 serum concentrations than the sham group. CONCLUSIONS: Heart failure-induced skeletal muscle atrophy is combined with fiber necrosis, increased MyoD gene expression and decreased myogenin protein levels.

Differential nutritional, endocrine, and cardiovascular effects in obesity-prone and obesity-resistant rats fed standard and hypercaloric diets.

BACKGROUND: This study tested whether rats with obesity induced by a hypercaloric diet (HD) present higher nutritional, endocrine, and cardiovascular disturbances compared with counterparts with obesity induced by overfeeding of a standard diet. An additional objective was to compare the isolated influence of HD on these parameters in lean and obese rats. MATERIAL/METHODS: Twenty Wistar-Kyoto rats were distributed into four groups: CD-lean, CD-obese, HD-lean, and HD-obese. CD (control diet) and HD groups received commercial standard chow and HD, respectively, for 20 weeks. The lean and obese groups included obesity-resistant and obesity-prone animals, respectively. Nutritional and metabolic evaluation involved measurement of calorie intake, dietary efficiency, body weight, adiposity, glycemia, triacylglycerol, insulin, and leptin. Cardiovascular evaluation included systolic blood pressure measurement, echocardiography, and analyses of myocardial morphology and myosin heavy-chain composition. RESULTS: In both diets, obesity was characterized by increased adiposity, hyperleptinemia, hypertriacylglycerolemia, hyperinsulinemia, and cardiomyocyte nuclear hypertrophy. HD promoted hyperleptinemia and cardiac remodeling, characterized by nuclear and ventricular hypertrophy, as well as improved systolic performance in both the obesity-prone and obesity-resistant biotypes. In contrast to HD-lean, HD-obese rats presented more accentuated endocrine responses, including hyperglycemia, lower glycemic tolerance, and hyperleptinemia as well as interstitial fibrosis compared with the CD-obese animals. CONCLUSIONS: This study confirmed the primary hypothesis that rats with HD-induced obesity present more accentuated nutritional and endocrine disturbances compared with their counterparts with obesity resulting from overfeeding. In addition, dietary effects were more important between the obese groups, supporting evidence of an interaction between diet and biotype.

Effects of AT1 receptor antagonism on interstitial and ultrastructural remodeling of heart in response to a hypercaloric diet.

Palatable hypercaloric feeding has been associated with angiotensin-II type 1 receptor (AT1R) stimulation and cardiac remodeling. This study analyzed whether AT1R antagonism attenuates cardiac remodeling in rats subjected to a palatable hypercaloric diet. Male Wistar-Kyoto rats were subjected to a commercial standard rat chow (CD) or a palatable hypercaloric diet (HD) for 35 weeks and then allocated into four groups: CD, CL, HD, and HL; L groups received losartan in drinking water (30 mg/kg/day) for 5 weeks. Body weight, adiposity, and glycemia were evaluated. The cardiovascular study included echocardiography, and myocardial morphometric and ultrastructural evaluation. Myocardial collagen isoforms Type I and III were analyzed by Western blot. Both HD and HL had higher adiposity than their respective controls. Cardiomyocyte cross-sectional-area (CD 285 ± 49; HD 344 ± 91; CL 327 ± 49; HL 303 ± 49 µm2 ) and interstitial collagen fractional area were significantly higher in HD than CD and unchanged by losartan. HD showed marked ultrastructural alterations such as myofilament loss, and severe mitochondrial swelling. CL presented higher Type I collagen expression when compared to CD and HL groups. The ultrastructural changes and type I collagen expression were attenuated by losartan in HL. Losartan attenuates systolic dysfunction and ultrastructural abnormalities without changing myocardial interstitial remodeling in rats subjected to a palatable hypercaloric diet.

Autonomic modulations of heart rate variability are associated with sports injury incidence in sprint swimmers.

OBJECTIVES: Young athletes' participation in competitive sports is becoming increasingly common, and this increased involvement raises concerns about the occurrence of overtraining and sports injuries. Since these issues are poorly understood, this study analyzed heart rate variability, stress/recovery relationship, and sports injury incidence during a training macrocycle of young sprint and endurance swimmers. METHODS: Thirty teenage swimmers (aged 12 to 17 years) were divided into two groups as follows: Sprint (n = 17) and Endurance (n = 13). Subjects were evaluated over 20 weeks, based on the following three schedules: general, specific, and competitive. In addition to heart rate variability and sports injury incidence, the Recovery-Stress-Questionnaire of Athletes was used to analyse stress/recovery states in athletes. All procedures were developed at the initial moment and at the end of each periodization step. RESULTS: The Sprint group presented a reduced standard deviation of normal-normal beats (73.0 ± 6.6 vs. 54.1 ± 3.5 ms; p < 0.05) and root mean square of the successive differences (55.3 ± 6.2 vs. 42.0 ± 3.7 ms; p < 0.01) from the period of general preparation until the time of competition. Recovery-stress monitoring was affected only by the swimming training periodization (p < 0.05). During the general period, differences between recovery and stress scales were correlated directly with the root mean square of the successive differences (r = 0.576; p = 0.001), the standard deviation of instantaneous variability beat-to-beat (r = 0.521; p = 0.003) and the triangular index (r = 0.476; p = 0.008). Differences between general recovery and stress scales were inversely correlated with geometric indexes after the specific training period. Moreover, the Sprint group showed a higher incidence of sports injury than the Endurance group (0.0214 ± 0.0068 vs. 0.0136 ± 0.0050 cases/1000 hours). CONCLUSION: Sprint training was associated with progressive activation of the sympathetic nervous system as well as a higher incidence of sports injury in comparison to endurance swimming during a training macrocycle.