Thyroid hormone induces restrictive cardiomyopathy in ß1-adrenoceptor knockout mice.

The purpose of this study was to characterize the role of ß1-AR signaling and its cross-talk between cardiac renin-angiotensin system and thyroid-hormone-induced cardiac hypertrophy. T3 was administered at 0.5 mg·kg-1·day-1 for 10 days in ß1-KOT3 and WTT3 groups, while control groups received vehicle alone. Echocardiography and myocardial histology was performed; cardiac and serum ANGI/ANGII and ANP and cardiac levels of p-PKA, p-ERK1/2, p-p38-MAPK, p-AKT, p-4EBP1, and ACE were measured. WTT3 showed decreased IVSTd and increased LVEDD versus WTsal (p < 0.05). ß1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus ß1-KOsal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WTT3 versus ß1-KOT3 (p < 0.05). Cardiac ACE expression was increased in T3-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or ß1-KOT3, p-4EBP1 was elevated in ß1-KO animals, and p-ERK1/2 was up-regulated in ß1-KOT3. These findings suggest that ß1-AR signaling is crucial for TiCH.

Effects of Resistance Training in Individuals with Lower Limb Amputation: A Systematic Review.

Individuals with lower-limb amputations may have a significant strength deficit. This deficit may be related to the stump length and can lead to changes in gait, reduced energy efficiency, walking resistance, altered joint load, and increased risk of osteoarthritis and chronic low back pain. This systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines to examine the effects of resistance training in lower limb amputees. Interventions with resistance training and other training methods were sufficient to achieve muscle strength gain in muscles of the lower limbs, improved balance, and improvements in gait pattern and speed when walking. However, it was impossible to determine from the results whether resistance training was mainly responsible for these benefits or even whether the positive effects presented would be observed with only this training method. When combined with other exercises, interventions with resistance training made possible gains for this population. Accordingly, it is noteworthy that the main finding of this systematic review is that the effects may be different according to the level of amputation, with mainly transtibial and transfemoral amputations studied.

Progression of heart failure is attenuated by antioxidant therapy with N-acetylcysteine in myocardial infarcted female rats.

This study investigated the therapeutic potential of N-acetylcysteine (NAC) in the treatment of heart failure in female rats. Myocardial infarcted (MI) rats were given NAC (250 mg/kg/day p.o.) during 28 days after surgery (MI + NAC) or vehicle (MI + Placebo), and sham-operated rats received the same treatments (Sham + NAC and Sham + Placebo). Electrocardiographic and echocardiographic analyses were performed in the last week of treatment. Cardiac mRNA levels of types I and II superoxide dismutase (SOD), catalase, types I and III glutathione peroxidase (GPX), nerve growth factor (NGF), ß1-adrenergic receptor (ß1ADR), and type 2 muscarinic receptor (M2R) were assessed. Cardiac levels NADPH oxidase (NOX) activity, total content of reduced thiols, and SOD, GPX, and catalase activity were assessed. Compared to MI + Placebo group, MI + NAC group exhibited decreased NOX activity, increased content of reduced thiols, increased GPX activity, and normalized GPX III mRNA levels (p < 0.05). Heart and lung weights, left ventricular (LV) end-diastolic volume and left atrium/aorta ratio were decreased, while LV posterior wall thickness and ejection fraction were increased in MI + NAC group versus MI + Placebo rats (p < 0.05). Power density of low frequency band was decreased, while power density of high frequency and the root mean square of the successive differences were increased in MI + NAC rats versus MI + Placebo (p < 0.05). These findings indicate that NAC promotes therapeutic effects in the progression of MI-induced heart failure in female rats.

Cardiac ischemia/reperfusion injury is inversely affected by thyroid hormones excess or deficiency in male Wistar rats.

AIM: Thyroid dysfunctions can increase the risk of myocardial ischemia and infarction. However, the repercussions on cardiac ischemia/reperfusion (IR) injury remain unclear so far. We report here the effects of hypothyroidism and thyrotoxicosis in the susceptibility to IR injury in isolated rat hearts compared to euthyroid condition and the potential role of antioxidant enzymes. METHODS: Hypothyroidism and thyrotoxicosis were induced by administration of methimazole (MMZ, 300 mg/L) and thyroxine (T4, 12 mg/L), respectively in drinking water for 35 days. Isolated hearts were submitted to IR and evaluated for mechanical dysfunctions and infarct size. Superoxide dismutase types 1 and 2 (SOD1 and SOD2), glutathione peroxidase types 1 and 3 (GPX 1 and GPX3) and catalase mRNA levels were assessed by quantitative RT-PCR to investigate the potential role of antioxidant enzymes. RESULTS: Thyrotoxicosis elicited cardiac hypertrophy and increased baseline mechanical performance, including increased left ventricle (LV) systolic pressure, LV developed pressure and derivatives of pressure (dP/dt), whereas in hypothyroid hearts exhibited decreased dP/dt. Post-ischemic recovery of LV end-diastolic pressure (LVEDP), LVDP and dP/dt was impaired in thyrotoxic rat hearts, whereas hypothyroid hearts exhibited improved LVEDP and decreased infarct size. Catalase expression was decreased by thyrotoxicosis. CONCLUSION: Thyrotoxicosis was correlated, at least in part, to cardiac remodeling and increased susceptibility to IR injury possibly due to down-regulation of antioxidant enzymes, whereas hypothyroid hearts were less vulnerable to IR injury.

Administration of an anabolic steroid during the adolescent phase changes the behavior, cardiac autonomic balance and fluid intake in male adult rats.

Few data are available on adolescent users because most behavioral studies on anabolic-androgenic steroids (AAS) abuse have been performed in adults. Studies evaluating the impact of long-term effects of AAS abuse on the prepubertal phase are even more uncommon. Accordingly, this study was developed to test the hypothesis that changes induced by the use of AAS during the adolescent phase may be noted in the adult phase even when the AAS treatment cycle is discontinued. Therefore, not only behavioral changes but also possible autonomic and electrolyte disorders were evaluated. For this purpose, we used male prepubertal, 26-day-old (P26) Wistar rats that were treated with vehicle (control, n=10) or testosterone propionate (TP; 5 mg/kg intramuscular (IM) injection, AAS, n=10) five times per week for 5 weeks, totaling 25 applications during the treatment. Aggression tests were performed at the end of the cycle (P54-56), whereas open-field tests (OFTs), elevated plus maze (EPM) behavioral tests and measurements of heart rate variability (HRV), fluid intake and pathology were conducted in the adult phase (P87-92). The AAS group showed greater aggressiveness in the pubertal phase and higher levels of horizontal and vertical exploration and anxiety-related behavior in the adult phase than the control group (P<0.05). HRV tests showed an increase in sympathetic autonomic modulation, and hydroelectrolytic assessment showed lower basal intake levels of hypertonic saline than the control group (P<0.05), without statistically significant changes in the basal intake of water. These data together suggest that the use of AAS during the prepubertal phase induces behavioral, autonomic and hydroelectrolytic changes that manifest in the adult phase even when treatment is discontinued in late adolescence in rats.