Splenic denervation worsens lipopolysaccharide-induced hypotension, hemoconcentration, and hypovolemia.
During lipopolysaccharide (LPS)-induced endotoxemia, increased intrasplenic fluid efflux contributes to a reduction in plasma volume. We hypothesized that splenic sympathetic nerve activity (SSNA), which increases during endotoxemia, limits intrasplenic fluid efflux. We reasoned that splenic denervation would exaggerate LPS-induced intrasplenic fluid efflux and worsen the hypotension, hemoconcentration, and hypovolemia. A nonlethal dose of LPS (150 microg x kg(-1) x h(-1) for 18 h) was infused into conscious male rats bearing transit time flow probes on the splenic artery and vein. Fluid efflux was estimated from the difference in splenic arterial inflow and venous outflow (A-V). LPS significantly increased the (A-V) flow differential (fluid efflux) in intact rats (saline -0.01 +/- 0.02 ml/min, n = 8 vs. LPS +0.21 +/- 0.06 ml/min, n = 8); this was exaggerated in splenic denervated rats (saline -0.03 +/- 0.01 ml/min, n = 7 vs. LPS +0.41 +/- 0.08 ml/min, n = 8). Splenic denervation also exacerbated the LPS-induced hypotension, hemoconcentration, and hypovolemia (peak fall in mean arterial pressure: denervated 19 +/- 3 mmHg, n = 10 vs. intact 12 +/- 1 mmHg, n = 8; peak rise in hematocrit: denervated 6.7 +/- 0.3%, n = 8 vs. intact 5.0 +/- 0.3%, n = 8; decrease in plasma volume at 90-min post-LPS infusion: denervated 1.08 +/- 0.15 ml/100 g body wt, n = 7 vs. intact 0.54 +/- 0.08 ml/100 g body wt, n = 8). The exaggerated LPS-induced hypovolemia associated with splenic denervation was mirrored in the rise in plasma renin activity (90 min post-LPS: denervated 11.5 +/- 0.8 ng x ml(-1) x h(-1), n = 9 vs. intact 6.6 +/- 0.7 ng x ml(-1) x h(-1), n = 8). These results are consistent with our proposal that SSNA normally limits LPS-induced intrasplenic fluid efflux.
Andrew
P S
PS
Departments of Physiology and Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Kaufman
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D020896:Hypovolemia / Q000139:chemically induced / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010953:Plasma Volume / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D013154:Spleen / Q000098:blood supply / Q000294:innervation* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D012083:Renin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine