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.

Introduction: High-intensity interval training (HIIT) has been recommended in post-myocardial infarction (MI) cardiac rehabilitation; however, its effects on MI-induced cardiac remodeling and skeletal muscle remain unclear. This study evaluated the effects of HIIT on functional capacity, cardiac remodeling, and the soleus skeletal muscle in rats after long-term MI. Methods: Three months after MI induction, Wistar rats were assigned to Sham, MI, and MI subjected to HIIT (MI-HIIT) groups. HIIT was performed three times per week for three months on a treadmill. Cardiac function and functional capacity were assessed before and after training. Oxidative stress markers, energy metabolism enzyme activities, and trophism were analyzed in the soleus. The statistical analysis included ANOVA and Bonferroni or Kruskal–Wallis and Dunn tests. Results: HIIT improved functional capacity compared to the Sham and MI groups. The infarcted groups had left ventricular dilation, hypertrophy, and systolic dysfunction, which were not modulated by HIIT. Soleus fiber cross-sectional areas did not differ between the groups. Catalase activity was lower in the MI and MI-HIIT groups than in the Sham group, while other oxidative stress markers were unchanged. HIIT increased citrate synthase activity compared to the Sham and MI groups, and phosphofructokinase and carnitine palmitoyltransferase-1 activities compared to the MI group. Conclusions: High-intensity interval training improves functional capacity despite unchanged cardiac remodeling in long-term infarcted rats. Enhanced physical capacity is associated with the increased activity of the enzymes involved in the energy metabolism of the soleus muscle.