Influence of N-acetylcysteine treatment on endotoxin-induced microcirculatory disturbances.
OBJECTIVE
To determine the influence of N-acetylcysteine (NAC) in a treatment model, its effects on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics in postcapillary venules of rat mesentery.


METHODS
Prospective, randomized, controlled, experimental study.


METHODS
Animal research laboratory.


METHODS
40 male Wistar rats.


METHODS
The rats randomly received one of four treatments: infusion of saline (SAL) or Escherichia coli lipopolysaccharides (LPS) followed by treatment with saline (SAL) or NAC (150 mg.kg-1 body weight) 30 min after induction of endotoxemia.


RESULTS
Leukocyte adherence, red blood cell velocity, and vessel diameters in postcapillary venules of rat mesentery were evaluated every 30 min over a period of 120 min using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate was calculated from red cell velocity, and vessel diameter. NAC in rats without endotoxemia (SAL + NAC group) compared to the control group (SAL + SAL) did not change microcirculatory parameters in postcapillary venules of rat mesentery. In both LPS-treated groups (LPS + SAL and LPS + NAC), leukocyte adherence increased after just 30 min. NAC treatment prevented a further increase in leukocyte adherence and attenuated the extravasation of fluorescence-labeled albumin during endotoxemia. Venular diameters remained unchanged, while erythrocyte velocity decreased in the LPS + SAL group. This led to a lower venular wall shear rate in this group.


CONCLUSIONS
Treatment with NAC attenuates endotoxin-induced leukocyte adherence and macromolecular leakage in postcapillary venules of rat mesentery, showing that NAC is also effective after the onset of endotoxemia.
Schmidt
W
W
Department of Anesthesiology, University of Heidelberg, Germany. werner.schmidt@urz.uni-heidelberg.de
Walther
A
A
Gebhard
M M
MM
Martin
E
E
Schmidt
H
H
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D019446:Endotoxemia / Q000097:blood / Q000503:physiopathology*; D004912:Erythrocytes / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014699:Venules / Q000187:drug effects*
D000111:Acetylcysteine