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 mediator s during extracorporeal circulation (EEC). ECC can be used to study th e potential protective effect of a pharmacon against neutrophil-mediat ed lung injury. Clinical studies have indicated that N-acetylcysteine (NAC) may improve systemic oxygenation and reduce the need for ventila tory support when given to patients with acute lung injury. Design: Ca rdiac 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. Patients: 18 patients who underwent ECC : group 1 (n = 8) no premedication (only placebo); group 2 (n = 10) NA C (72 mg/kg i.v. as a bolus, later 72 mg/kg over 12 h). Measurements a nd results: In group 2, the partial pressure of oxygen in arterial blo od fractional inspired oxygen 4 h after surgery was significantly high er than in group 1 (213 +/- 31 vs 123 +/- 22; p = 0.044). NAC pretreat ment 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 = 0.02 7). 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: 67 1 +/- 72 ng/ml vs group 2: 579 +/- 134; p = 0.37) and complex formatio n between elastase and alpha(1)-proteinase inhibitor were no different in the two groups. There were no significant differences in cellular composition and mediators in the lavage fluid, although values for tot al number of neutrophils, elastase, MPO and interleukin-8 were lower i n group 2. Conclusion: Pretreatment with NAC may prevent lung injury b y diminishing elastase activity. Since the release of mediators, espec ially MPO, is not affected, this diminished activity of elastase may b e achieved by enhanced inactivation by antiproteases after initial tre atment.