Although current guidelines recommend resistance exercise in combination with aerobic training to increase muscle strength and prevent skeletal muscle loss during cardiac remodeling, its effects are not clear. In this study, we evaluated the effects of resistance training on cardiac remodeling and the soleus muscle in long-term myocardial infarction (MI) rats. Methods: Three months after MI induction, male Wistar rats were assigned to Sham (n = 14), MI (n = 9), and resistance exercised MI (R-MI, n = 13) groups. The rats trained three times a week for 12 weeks on a climbing ladder. An echocardiogram was performed before and after training. Protein expression of the insulin-like growth factor (IGF)-1/protein kinase B (Akt)/rapamycin target complex (mTOR) pathway was analyzed by Western blot. Results: Mortality rate was higher in MI than Sham; in the R-MI group, mortality rate was between that in MI and Sham and did not differ significantly from either group. Exercise increased maximal load capacity without changing cardiac structure and left ventricular function in infarcted rats. Infarction size did not differ between infarcted groups. Catalase activity was lower in MI than Sham and glutathione peroxidase lower in MI than Sham and R-MI. Protein expression of p70S6K was lower in MI than Sham and p-FoxO3 was lower in MI than Sham and R-MI. Energy metabolism did not differ between groups, except for higher phosphofrutokinase activity in R-MI than MI. Conclusion: Resistance exercise is safe and increases muscle strength regardless structural and functional cardiac changes in myocardial-infarcted rats. This exercise modality attenuates soleus glycolytic metabolism changes and improves the expression of proteins required for protein turnover and antioxidant response.

Acute myocardial necrosis activates the immune response and inflammatory processes. Although the initial response is helpful in restoring tissue injury, dysregulated and exacerbated inflammation contributes to the progression of cardiac remodeling. Inflammasomes play important roles in post-infarction inflammation. NALP1/NLRP1, NLRP 3, and NLRC4 are the best-known inflammasomes. NLRP3, which has received the most study in cardiovascular disease, has been linked to increased IL-1β (IL1B) production and caspase-1 activity, as well as impaired cardiac function. The role of NLRP1 and NLRC4 inflammasomes after acute myocardial infarction (MI) is poorly understood. We evaluated the expression of myocardial inflammasomes and inflammatory markers 72 h after MI in rats. Male Wistar rats were divided into Sham (n = 15) and MI (n = 16) groups. MI was induced by ligating the left anterior descending coronary artery. Infarct size was assessed by histology. Myocardial protein and gene expression was analyzed by Western blot and RT-qPCR, respectively. IL-1β (Il1b) concentrations in serum and heart macerate supernatant were evaluated by ELISA. Statistical analysis was performed using Student’s t test. Rats with an MI size less than 30% of the total left ventricle (LV) area were excluded; infarct size was 46 ± 11% of the total LV area in MI. The interstitial collagen fraction was higher in MI. Nlrc4, caspase-1 (Casp1), and IL-1β (Il1b) protein expressions were higher in MI. Nlrp3, Nlrp1, ASC (Pycard), pro-caspase-1, and pro-IL-1β (Il1b) expressions did not differ between groups. Expression of the Nlrp3 and ASC (Pycard) genes, as well as myocardial and serum IL-1β (Il1b) concentrations, was higher in MI. Acute post-myocardial infarction inflammation is characterized by increased protein expression of Nlrc4, caspase-1, and interleukin-1β; increased gene expression of Nlrp3 and ASC (Pycard); and elevated serum and myocardial concentrations of interleukin-1β in combination with an increased myocardial collagen interstitial fraction.

Substances released by cardiomyocytes after myocardial infarction (MI) lead to inflammasome assembly. Heart failure (HF) is associated with skeletal muscle inflammation. Methotrexate (MTX) reduces cardiovascular outcomes in chronic inflammation patients. Lipid core nanoparticle-associated MTX (MTX-LDE) attenuated cardiac remodeling in MI rats. We investigated the effects of early MTX-LDE administration on cardiac remodeling and inflammasomes in soleus muscle of MI rats. Wistar rats were separated into Sham, MI, and MI-MTX groups. MTX was initiated 24 h after MI at 1 mg/kg/week intraperitoneally for 10 weeks. Soleus protein expression of NLRP1, NLRP3, NLRC4, ASC, procaspase-1, Caspase-1, pro-IL-1β, and IL-1β was quantified by Western blotting; Nlrp1a, Nlrp3, Nlrc4, Pycard (Asc), Casp1, and Il1b gene expression was assessed by qPCR; and statistical analysis used Student’s t test and ANOVA. Rats with infarction size > 35% total left ventricle (LV) area were included in the study; infarction size did not differ between groups. Echocardiogram showed infarcted groups with LV dilation and dysfunction. Diastolic function was worse in MI-MTX than MI. NLRP1 and NLRC4 protein expression was lower in MI-MTX than Sham. Expression of other proteins and gene expression did not differ between groups. Early MTX-LDE administration reduces NLRP1 and NLRC4 protein expression in soleus muscle without improving cardiac remodeling in rats.