Cardio‐respiratory patterning varies during E. coli peritonitis in Sprague‐Dawley male rats

Abstract

Sepsis is distinguished by an overwhelming uncontrolled inflammatory response to a pathogen (e.g. Escherichia coli, E. coli). The interval from the onset of sepsis to treatment is a critical factor for patient survival. We hypothesize that ventilatory pattern variability (VPV; autocorrelation coefficient (r), Mutual Information, (MI), Sample Entropy (SampEn) and nonlinear complexity index (NLCI)), respiratory frequency (fR), and cardio-ventilatory coupling (CVC) are biometrics that vary with neural inflammation and may signal the onset of a sepsis. Male, Sprague Dawley rats (n=35) received surgically implanted pressure transducers (DSI telemetry; arterial blood pressure, (BP)), allowed 2wks to recover, then placed unanesthetized in whole-body plethysmography (Buxco) set on a receiver (EMKA) for baseline (0h) recordings. Then, we implanted them with a thrombin-fibrinogen pellet, which was either sterile (D0) or contained 25 x 106 CFU E. coli (D25). After inoculation, we recorded ventilation at 3h (D0 n=5, D25 N=5), 6h (D0 n=3, D25 n=5), 15h (D0 n=4, D25 n=4), 24h (D0 n=4, D25 n=5) and analyzed fR, VPV & CRC. We tested for differences with a 2-way, repeated-measures ANOVA, both within groups between 0h and each hour and between D0 and D25 at each hour. fR did not differ from 0h or between D0 and D25 by 3, 6 and12h; but increased by 24h (D0 and D25 (p<001)). Similarly, VPV became more predictable by 15h D25 (r at 1 cycle length, D0 0.59 ± 0.08 vs 0.69 ± 0.201, p<0.001; MI, D0 0.37 ± 0.100 vs D25 0.49 ± 0.11 bits, p<.001; and NLCI, D0 0.08 ± 0.05 vs D25 0.15 ± 0.04 p<0.001). CVC changed, in the distribution (χ2) of the intervals between the peak of the R-wave the transition from expiration-to-inspiration phase switch (EIPS) by 15h for D25 (D0, 66.3 ± 53.1 vs D25, 31.2 ± 19.1, p< 0.001). Transformed relative Shannon entropy (tRSE) for the R-wave-to-EIPS intervals did not differ at any time point. Heart rate (HR) changed at 15hr for D25 (D0, 400 ± 47 vs D25, 445 ± 33, p<0.001). These results suggest that fR, VPV and CVC biometrics change as systemic infection progresses and may be useful measures of sepsis progression over time in critically ill patients.