Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis

Abstract

Background: Sepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood.

Methods: Sepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared with healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels, as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-), and magnesium (Mg2+).

Results: ACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. Whereas plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis.

Conclusions: CLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone, and aldosterone levels. In addition, electrolyte levels showed significant disturbances after CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis.

Figure 1

Hormonal changes of the HPA-axis following experimental sepsis. (A) Plasma levels obtained from healthy rats (neg ctrl) or septic littermates (6-48 hrs after CLP). (B) Plasma samples from septic animals were obtained 6-48 hrs after CLP and compared with healthy rats. (C) Aldosterone concentrations were assessed as a function of time in septic vs. healthy rats. All samples were analyzed by ELISA. n = 5-10 per experimental condition.

Figure 2

Electrolyte levels during experimental sepsis. Plasma samples were obtained and evaluated with a standardized chemistry analyzer for electrolyte levels as a function of time after CLP. Healthy animals served as negative controls. Electrolytes assessed include sodium (A), potassium (B), chloride (C), and magnesium (D). n = 5-10 per experimental condition.