Estrus Cycle Stages Differentially Alter Ventilatory Pattern Variability (VPV) in Septic Female Rats

Abstract

The sex hormones, estrogen and progesterone, affect central respiratory control. Progesterone, increases respiratory frequency (fR). Sepsis, a disease process caused by a dysregulated systemic inflammatory response, also affects respiratory control that can be quantified by Ventilatory Pattern Variability (VPV). We hypothesized that natural hormone fluctuations during the female estrus cycle affect VPV and its differential control during sepsis. The estrus cycle of female Sprague Dawley rats (n = 19) was assessed by collecting, hematoxylin/eosin staining, and identifying vaginal epithelial cells. Proestrus, in which progesterone peaks, was determined by the absence of both leukocytes and cornified multinucleated epithelial cells. Rats were inoculated with fibrin pellets containing 0 (D0) or 100x 10^ 6 (D100) E. coli cells during proestrus. Before and 12 h after inoculation, we recorded the ventilatory pattern in conscious unrestrained rats using whole‐body plethysmography. VPV [coefficient of variation (CV) for the duration of the respiratory cycle (CV‐Ttot), autocorrelation function (AC), mutual information (MI), sample entropy (SampEn), and nonlinear complexity index (NLCI)] was compared across four experimental groups: 1) D0 proestrus rats (n = 3), 2) D100 proestrus rats (n = 7), 3) D0 non‐proestrus rats (n = 4), and 4) D100 non‐proestrus rats (n = 5) using one‐way analysis of variance (ANOVA). In the non‐proestrus groups, SampEn was greater in D0 than D100 (1.31±0.011 vs 1.14±0.002 Nats, p = 0.006), but in proestrus rats, SampEn did not vary with inoculation (D0, 1.26±0.003 vs D100, 1.26±0.004 Nats, NS). However, CV‐Ttot, AC and MI trended toward but did not reach significance given the low n. These preliminary data suggest that a decrease in VPV due to septicemia occurs in nonproestrus stages, whereas did not occur in proestrus.Support or Funding InformationFunded By: VA Research Service (I01BX004197); NIH (U01 EB021960)