Impairment of bacterial clearance induced by norepinephrine infusion in rabbits.
OBJECTIVE
Purpose of the study was to investigate the potential influence of norepinephrine (NE) on immune functions in terms of systemic and organ-specific bacterial clearance in rabbits.


METHODS
To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) CFU) were injected intravenously 60 min after starting the NE infusion at a low dose (1 microgram/kg per min, n = 6), causing an increase (30 mmHg) in mean arterial pressure without affecting the oxygen uptake, and at a higher dose (7.5 micrograms/kg per min, n = 6), resulting in a marked decrease (20%) in oxygen uptake, after infusion of NaCl solution (control, n = 6). In additional experiments (n = 6) NE (1 microgram/kg per min) was tested in endotoxemia induced by simultaneous infusion of endotoxin (40 micrograms/kg per h). Parameters monitored were arterial pressure, oxygen uptake, and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were sacrificed, and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts.


RESULTS
NE infusion resulted in a dose-dependent prolonged elimination of the injected E. coli from the blood and in significantly higher (p < 0.05) numbers of CFU in liver and lung compared to the controls. Significant impairment of bacterial clearance was found after shock-producing endotoxemia, whereas simultaneous infusion of NE and endotoxin caused only a slightly delayed blood clearance of the injected bacteria.


CONCLUSIONS
NE dose dependently affected bacterial clearance, which might be due to ischemia-derived hypoxic impairment of the phagocytosis and lysis function of the reticuloendothelial system, whereas NE improved elimination of bacteria in a state of endotoxic shock.
Koch
T
T
Department of Anesthesiology and Operative Intensive Care Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.
Heller
S
S
van Ackern
K
K
Schiefer
H G
HG
Neuhof
H
H
D000818:Animals; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000502:physiology* / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D012772:Shock, Septic / Q000276:immunology* / Q000382:microbiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D009638:Norepinephrine