Escherichia Coli Induced Peritonitis Alters the Central Respiratory Network

Abstract

Severe septic patients manifest respiratory failure and ventilator dependence, both of which we theorize relate to brainstem inflammation leading to dysfunction of the respiratory control network. Brainstem inflammation mirrors the systemic inflammation, associated with sepsis. Here, we hypothesize that dose dependent E. coli peritonitis induce neuroinflammation that alters the central respiratory network. For this AAALAC approved study, ventilatory pattern of awake pups (Sprague Dawley males, n=28, P24-P27) were recorded using whole-body plethysmography for 1h before (Baseline, Bsln) and 24h after implantation surgeries (T24). Fibrin clots containing either 5x106 (D5, n=10) or 2.5x106 (D2.5, n=9) or 0 (D0, n=9) E. coli cells were implanted in the peritoneal cavity. After 24h, ventilatory pattern was recorded and the animal immediately prepared for the in situ preparation where phrenic nerve (PNA), cervical vagus nerve (VNA), thoracic sympathetic chain (tSNA) activities, heart rate and perfusion pressure were recorded. Respiratory pattern was recorded for 10 min to assess differences in patterning between groups. Whole-body plethysmography revealed that 24h after surgery implantation only the group of D5 (TE (time of expiration) 0.24±0.03, p=0.005; TTOT (Total time of respiratory cycle) 0.40±0.02, p=0.008; fR (respiratory frequency) 155± 11, p=0.015) differed compared to D2.5 (TE 0.31±0.02; TTOT 0.50±0.02; fR 122±6) and D0 (TE 0.32±0.02; TTOT 0.505±0.03; fR121± 6). Although no significant changes for the nonlinear complex index (NLCI) were identified between the groups, NLCI trended upwards for both D2.5 (0.100±0.02) and D5 (0.106±0.02) when compared to D0 (0.064±0.01, p=0.136). In the in situ brainstem-spinal cord preparation both D2.5 (TPI (time of Post-inspiration) 2.89±0.40, p=0.002; TTOT 4.25±0.34, p=0.002; fR 14.8± 0.90, p=0.002) and D5 (TPI 3.01±0.16, p<0.001; TTOT 4.37±0.18, p=0.001; fR13.90± 0.50, p=0.004) differed from D0 (TPI 3.01±0.41; TTOT 5.98±0.39; fR 10.60± 0.80), but did not differ from each other. From this data, we conclude that E. coli peritonitis induce changes in breathing pattern that persist in the in situ preparation. Further increase in inoculate does not lead to increased disordered breathing.