Sepsis progression and multiple organ dysfunction in rats: carotid body involvement (873.5)

Abstract

Sepsis syndromes involve pathological processes often leading to multiple organ dysfunction (MOD) and death. Sepsis progresses to MOD due uncontrolled release of inflammatory mediators. Lately, increasing evidence supports the idea that the carotid body both regulates the immune status and plays a protective role during sepsis syndromes. In anaesthetized (pentobarbitone, 60 mg/kg IP) male Sprague‐Dawley rats (BW 100±20 g) we measured plasma levels of cytokines, chemokines and MOD‐markers, 90‐min after IP administration of either saline or 15 mg/kg LPS in control (SHAM surgery; intact carotid/sinus nerves) and in bilateral carotid chemo/baro‐denervated rats (BCN). Respiratory frequency (fR) and heart rate (fH) were augmented in SHAM‐LPS group, but systolic blood pressure (PS) dropped. BCN decreases the survival time of rats and blunts the fR response to LPS but enhancing both, the fH increase and the PS fall. SHAM‐LPS and BCN‐LPS rats shown increased plasma levels of IL‐1β, IL‐10, and TNF‐α; however, the increase in both ILs was lower in BCN‐LPS, which also had augmented IL‐2 levels. Unchanged cortisol plus increased levels of epinephrine can be related to increased plasma levels of TNF‐α. Finally, BCN‐LPS induced an early onset of MOD identified by increased plasma levels of creatine kinase, amylase, creatinine, neutrophil gelatinase‐associated lipocaline, total bilirrubin and alanine aminotransferase. We propose that carotid body would modify the inflammatory response during sepsis syndromes through a communication network involving neural, humoral, and cytokine components, and also would play a protective role in the sepsis progression to MOD.Grant Funding Source: Supported by: FONDECYT 1120976 and UNAB DI‐354‐13/R (to RF) and UDD CI 23400098 (to PR)