Abstract

Sepsis is an overwhelming systemic infection that leads to cardio‐respiratory failure and is associated with the loss of heart rate variability (HRV). The mechanisms by which the immune response to sepsis affects HRV, in particular cardio‐respiratory coupling (CRC), are unclear. We hypothesize that expression of pro‐inflammatory cytokines in the nucleus tractus solitarius (nTS) disrupts CRC. To begin to test this hypothesis, adult male Sprague Dawley rats (n=6) were anesthetized with isoflurane, and diaphragmatic EMG and ECG were recorded. After a 30‐min ‘baseline’ recording, lipopolysaccharide (LPS) (24 mg/kg) or saline was injected intraperitoneally. After 6h, respiratory and heart rates increased relative to baseline in LPS‐ but not saline‐treated rats. Coefficient of variation did not change in either group. Immunostaining revealed upregulation of IL‐1β in nTS. Cardioventilatory coupling was assessed by chi‐squared analysis of single‐ordered histograms. After LPS injection, chi‐squared value decreased from 71.5 ± 0.92 to 36.6 ± 12.3 (mean ± SD, p<0.01). We conclude that IL‐1β expression in the nTS is associated with cardiorespiratory uncoupling in sepsis. These data support the concept that CRC, in addition to HRV, could serve as a biomarker for health status and affects gas‐exchange efficiency contributing to cardio‐respiratory function.

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