N-acetylcysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid.
OBJECTIVE
Study of leukocyte activation and release of toxic mediators during extracorporeal circulation (ECC). ECC can be used to study the potential protective effect of a pharmacon against neutrophil-mediated lung injury. Clinical studies have indicated that N-acetylcysteine (NAC) may improve systemic oxygenation and reduce the need for ventilatory support when given to patients with acute lung injury.


METHODS
Cardiac surgery patients were pretreated with high-dose NAC in order to assess the potential role of NAC to interfere with neutrophil-mediated inflammation and lung injury.


METHODS
18 patients who underwent ECC: group 1 (n = 8) no premedication (only placebo); group 2 (n = 10) NAC (72 mg/kg i.v. as a bolus, later 72 mg/kg over 12 h).


RESULTS
In group 2, the partial pressure of oxygen in arterial blood/fractional inspired oxygen 4 h after surgery was significantly higher than in group 1 (213 +/- 31 vs 123 +/- 22; p = 0.044). NAC pretreatment prevented an increase in plasma neutrophil elastase activity (18.9 +/- 6.9 vs 49.9 +/- 5.6 ng/ml in group 1 at the end of ECC; p = 0.027). Release of myeloperoxidase (MPO) was not affected (group 1:1105 +/- 225 ng/ml vs group 2:1127 +/- 81 at the end of ECC; p = 0.63). At the end of ECC, total antigenic human neutrophil elastase (group 1:671 +/- 72 ng/ml vs group 2:579 +/- 134; p = 0.37) and complex formation between elastase and alpha 1-proteinase inhibitor were no different in the two groups. There were no significant difference in cellular composition and mediators in the lavage fluid, although values for total number of neutrophils, elastase, MPO and interleukin-8 were lower in group 2.


CONCLUSIONS
Pretreatment with NAC may prevent lung injury by diminishing elastase activity. Since the release of mediators, especially MPO, is not affected, this diminished activity of elastase may be achieved by enhanced inactivation by antiproteases after initial treatment.
De Backer
W A
WA
Department of Respiratory Medicine, University of Antwerp (UIA), Antwerpen-Wilrijk, Belgium.
Amsel
B
B
Jorens
P G
PG
Bossaert
L
L
Hiemstra
P S
PS
van Noort
P
P
van Overveld
F J
FJ
D000111:Acetylcysteine / Q000627:therapeutic use*; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011292:Premedication; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology / Q000276:immunology
D016166:Free Radical Scavengers; D019272:Leukocyte Elastase; D000111:Acetylcysteine