Sympathetic modulation of intestinal microvascular blood flow oscillations in experimental endotoxemia

Abstract

Impairment of the intestinal microcirculation has been recognized as an important factor in the pathogenesis of endotoxin related sepsis syndrome. We investigated the effects of endotoxemia on the variability of intestinal microvascular blood flow (IMBF) and arterial blood pressure (BP) in a prospective, randomized, controlled animal study. Recordings of IMBF (laser Doppler fluxmetry) and BP were performed before, two and four hours after i.v. injection of either placebo or endotoxin (5 mg/kg b.w. lipopolysaccharide from E. coli, serotype O55:B5). Control experiments were performed with systemic (clonidine) and local intestinal (surgery) sympathectomy. Spectral analysis was performed using the autoregressive approach. Spectral power was determined in two frequency bands (low frequency (LF): 0.27–0.74 Hz; high frequency (HF): 0.76–3.00 Hz). Two hours after endotoxin challenge a significant decrease in IMBF was observed. LF spectral power of IMBF and BP increased significantly in the endotoxin challenged group, while no effects were observed in the placebo group. Four hours after endotoxin administration IMBF decreased further and LF spectral power of IMBF and BP remained elevated. Denervation prevented the decrease in IMBF but did not abolish the LF power increase. Clonidine administration attenuated the IMBF decrease and significantly diminished the increase in LF spectral power of IMBF and BP. We conclude that endotoxemia is associated with increased sympathetic outflow to the systemic vasculature, as indicated by the increase in LF spectral power of arterial blood pressure. The increase in LF variability of IMBF is secondary to the increase in LF spectral power of BP, since it could be attenuated by systemic and not by local intestinal sympathectomy.