Right atrium cholinergic deficit in septic rats

Heart rate variability (HRV) is mainly determined by the influence of both branches of the Autonomic Nervous System over the sinus node. Low HRV has been associated with a worse prognosis in patients with sepsis. The objective of this study was to explain the reduction in HRV during experimental sepsis in adult rats. We recorded the heart's electrical activity by telemetry in conscious unrestrained male rats before and 1day after the induction of peritonitis (N=39) or sham peritonitis (N=15). Then, we analyzed the chronotropic responsiveness of the isolated heart to the autonomic neurotransmitters and determined catecholamine concentrations in blood plasma and acetylcholine and choline concentrations in the right atrium. The surviving septic rats (N=33) had increased heart rate (HR) and diminished HRV. Despite the higher HR in situ, the spontaneous basal HR in septic and sham isolated hearts was the same. The isolated septic hearts showed acetylcholine hypersensitivity (log (IC50,M)=-7.2±0.2 vs. -6.0±0.4, P=0.025) and lower concentrations of choline in their right atriums (in nMol/mg protein: 0.6±0.1 vs. 1.6±0.6, P=0.013). Norepinephrine concentration in blood plasma from septic rats was higher (in ng/ml: 29.2±8.4 vs. 5.8±4.1, P=0.019). In conclusion, septic rats present a deregulation of the autonomic nervous system, not only sympathetic overexcitation but also parasympathetic dysfunction.