The brief methylprednisolone administration is crucial to mitigate cardiac dysfunction after myocardial infarction.

Acute myocardial infarction (AMI) is one of the major causes of heart failure and mortality. Glucocorticoids administration post-infarction has long been proposed, but it has shown conflicting results so far. This controversy may be associated with the glucocorticoid type and the period when it is administered. To elucidate these, the present aims to evaluate if the brief methylprednisolone acetate administration is determinant for heart adaptation after AMI. Male Wistar rats were divided into 3 groups: sham-operated (SHAM); infarcted (AMI); infarcted treated with methylprednisolone acetate (AMI+M). Immediately after surgery, the AMI+M group received a single dose of methylprednisolone acetate (40 mg/kg i.m.). After 56 days, the cardiac function was assessed and lungs, liver and heart were collected to determine rates of hypertrophy and congestion. Heart was used for oxidative stress and metalloproteinase activity analyses. Methylprednisolone acetate attenuated matrix metalloproteinase-2 activity, cardiac dilatation, and prevented the onset of pulmonary congestion, as well as avoided cardiac hypertrophy. Our data indicate that administration of methylprednisolone acetate shortly after AMI may be a therapeutic alternative for attenuation of detrimental ventricular remodeling.

Photobiomodulation and Physical Exercise Modulate of Cell Survival Proteins in the Skeletal Muscle of Rats with Heart Failure and Diabetes Mellitus.

Introduction: Heart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity. Objective: To verify the influence of physical exercise and the association with PBM on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2. Materials and Methods: Male rats were assigned to one of four groups: control (CT), HF+DM (disease model), exercise+HF+DM (EX+HF+DM), and EX+HF+DM+PBM (EX+HF+DM+PBM). To induce DM2, we administered streptozotocin (STZ) (0.25 mL/kg, intraperitoneally). HF was induced by coronary ligation. One week post-induction, an 8-week aerobic exercise and PBM protocol was initiated. Western blot analysis was used to measure the expression of apoptosis-related proteins and autophagy. Results: The EX+HF+DM+PBM group showed a substantial increase in Nrf2, p-AKT, and LC3-I levels compared to the HF+DM group. Conclusions: These findings suggest that physical exercise combined with PBM can upregulate proteins that promote myocyte survival in rats with HF and DM2.

Photobiomodulation improves cell survival and death parameters in cardiomyocytes exposed to hypoxia/reoxygenation.

INTRODUCTION: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Ischemic heart disease is one of the most harmful conditions to cellular structure and function. After reperfusion treatment, a spectrum of adverse effects becomes evident, encompassing altered cell viability, heightened oxidative stress, activated autophagy, and increased apoptosis. Photobiomodulation (PBM) has been utilized in experimental models of cardiac hypoxia to enhance mitochondrial response and ameliorate biochemical changes in injured tissue. However, the effects of PBM on cultured cardiomyocytes subjected to hypoxia/reoxygenation are not yet well established. METHOD: H9C2 cardiomyocytes were exposed to hypoxia with concentrations of 300 µM CoCl2 for 24 h, followed by 16 h of reoxygenation through incubation in a normoxic medium. Treatment was conducted using GaAIAs Laser (850 nm) after hypoxia at an intensity of 1 J/cm2. Cells were divided into three groups: Group CT (cells maintained under normoxic conditions), Group HR (cells maintained in hypoxia and reoxygenation conditions without treatment), Group HR + PBM (cells maintained in hypoxia and reoxygenation conditions that underwent PBM treatment). Cell viability was analyzed using MTT, and protein expression was assessed by western blot. One-way ANOVA with the Tukey post hoc test was used for data analysis. Differences were significant when p < 0.05. RESULTS: PBM at an intensity of 1 J/cm2 mitigated the alterations in cell survival caused by hypoxia/reoxygenation. Additionally, it significantly increased the expression of proteins Nrf2, HSP70, mTOR, LC3II, LC3II/I, and Caspase-9, while reducing the expression of PGC-1α, SOD2, xanthine oxidase, Beclin-1, LC3I, and Bax. CONCLUSION: PBM at intensities of 1 J/cm2 reverses the changes related to oxidative stress, mitochondrial biogenesis, autophagy, and apoptosis caused by hypoxia and reoxygenation in a culture of cardiomyocytes.

The progression of pulmonary arterial hypertension induced by monocrotaline is characterized by lung nitrosative and oxidative stress, and impaired pulmonary artery reactivity.

The time-course of pulmonary arterial hypertension in the monocrotaline (MCT) model was investigated. Male rats were divided into two groups: MCT (received a 60 mg/kg i.p. injection) and control (received saline). The MCT and control groups were further divided into three cohorts, based on the follow-up interval: 1, 2, and 3 weeks. Right ventricle (RV) catheterization was performed and RV hypertrophy (RVH) was estimated. The lungs were used for biochemical, histological, molecular, and immunohistochemical analysis, while pulmonary artery rings were used for vascular reactivity. MCT promoted lung perivascular edema, inflammatory cells exudation, greater neutrophils and lymphocytes profile, and arteriolar wall thickness, compared to CTR group. Increases in pulmonary artery pressure and in RVH were observed in the MCT 2- and 3-week groups. The first week was marked by the presence of nitrosative stress (50% moderate and 33% accentuated staining by nitrotyrosine). These alterations lead to an adaptation of NO production by NO synthase activity after 2 weeks. Oxidative stress was evident in the third week, probably by an imbalance between endothelin-1 receptors, resulting in extracellular matrix remodeling, endothelial dysfunction, and RVH. Also, it was found a reduced pulmonary arterial vasodilatory response to acetylcholine after 2 (55%) and 3 (45%) weeks in MCT groups. The relevance of this study is precisely to show that nitrosative and oxidative stress predominate in distinct time windows of the disease progression.