Dynamics of Ventilatory Pattern Variability (VPV), Cardio‐Respiratory Coupling (CRC) and Cytokines in an E. coli Sepsis Model

Abstract

Cardio‐respiratory control is disrupted in sepsis. We hypothesized that increases in inflammatory cytokines that are expressed in the brainstem in a rat model of Escherichia coli (E. coli) peritonitis would correlate with decreases in VPV and the uncoupling of CRC. We implanted fibrin clots containing either 25×106 or 0 E. coli in the peritoneal cavity of chronically instrumented, adult Sprague‐Dawley Rats (n=19). We recorded cardiorespiratory patterns of awake, freely moving rats at 3, 6, 12, 24, and 48 hours after implantation. At each time point, blood, bronchoalveolar lavage fluid (BALF), peripheral and central nervous system (CNS) tissues were collected to measure cytokine concentrations. We quantified VPV and CRC using a set of complementary measures sensitive to both linear and nonlinear dynamics. We measured interleukin 1β (IL‐1b), interleukin 6 (IL‐6) and tumor necrosis factor α (TNF‐a) concentrations in serum, BALF and tissue supernatants by Luminex assay. Compared to the sham group, infected rats developed a systemic inflammatory response by 3h [increased serum IL‐6 (p<0.05), IL‐1b (p=0.05)], which peaked at 6h and then decreased progressively. Also, brainstem inflammation was evident at 3h post inoculation, with increases in IL‐1β in the medulla (p<0.01) and pons (p<0.05). Brainstem inflammation was associated with increased predictability in VPV, indicated by increases in mutual information (p<0.05) and nonlinear complexity index (NLCI). In our initial analysis of CVC (n=8 rats at 24h), the X2 values of the distribution of R‐wave timings relative to the onset of inspiration were highly significant but were not different between sham and septic groups. We conclude that decreases in VPV (i.e., increased pattern predictability) were present early in the course of systemic inflammation following E. coli infection in rats and these changes were associated with elevated serum and brainstem cytokines. In contrast, the persistence of CVC in the inoculated rats was unexpected; however, at 24h the NLCI was decreasing indicating that these rats may be recovering from the peritonitis.Support or Funding InformationVA Research Service (I01BX004197); NIH (U01 EB021960)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.