Effects of ketone body supplementation on cardiac remodeling induced by the Sepsis model in rats

Abstract

Sepsis is characterized by organ dysfunction caused by a dysregulated host response to infection. In septic shock, sepsis is associated with worsening circulatory, cellular, and metabolic dysfunction that dramatically increases the risk of death. The effects of septic shock on the cardiovascular system are well studied in the literature, and the resulting cardiac dysfunction is termed septic cardiomyopathy. Several pathways are involved in sepsis-induced myocardial injury, including production of reactive oxygen species (ROS), mitochondrial dysfunction, alteration of microRNAs (miRNAs) expression, alterations in the intestinal microbiota, in the metabolic profile and changes in energy metabolism. The cardiac changes resulting from these events are called cardiac remodeling. Among other substrates for energy production by the myocardium, ketone bodies stand out for providing an additional source of fuel for the myocardium when fatty acids and glucose cannot fully meet energy needs, as occurs in cardiac remodeling. In this scenario, ketone body supplementation may represent a promising strategy, with ²-hydroxybutyrate (²-OHB) being the most abundant and studied ketone body. Therefore, the aim of this study is to investigate the effect of ketone supplementation on cardiac remodeling and mortality in the model of sepsis induced by cecal ligation and puncture in rats. Male Wistar rats will be submitted to the sepsis induction model and then divided into 4 groups: Sham control (n=25), Sham with ketone supplementation (n=25), Sepsis control (n=25) and Sepsis with supplementation of ketone bodies (n=25). Euthanasia will be performed after seven days, followed by morphological, functional and biochemical tests. More specifically, the expression of miRNAs, metabolic profile, oxidative stress and intestinal microbiota will be evaluated. Values will be expressed as mean ± standard deviation and comparisons will be performed using the two-way ANOVA test with a significance level of 5%. (AU)