COMPARABLE EFFECTS OF HOCL AND OF FMLP-STIMULATED PMN ON THE CIRCULATION IN AN ISOLATED LUNG MODEL

Polymorphonuclear leukocytes (PMN) are involved in acute lung injury d uring adult respiratory distress syndrome (ARDS) via several mechanism s. This study focuses on neutrophil-derived oxidative stress. The infl uence of (A), continuous hypochlorous acid (HOCl) infusion over 105 mi n and (B) stimulation of PMN having been delayed in the pulmonary micr ovasculature were studied. Therefore pulmonary artery pressure (PAP), capillary filtration coefficient (K-f,K-c), and fluid retention (Delta W) were monitored using isolated rabbit lungs. These models (A/B) wer e compared with each other to assess the reproducibility of neutrophil -derived oxidative stress by HOCl. A: Infusion of 250/500/1,000/2,000 nmol/min HOCl (n = 6/group) evoked a Delta PAP(max) of 0.4 +/- 0.07/2. 4 +/- 0.21/4.9 +/- 0.29/4.6 +/- 0.25 mm Hg at 105/105/56.4 +/- 5.6/21. 5 +/- 0.8 min and a tenfold increase in K-f,K-c/Delta W at 60 min. B: Stimulation of PMN (1,480 +/- 323/mu l, n = 8), which were added into the perfusate and sequestrated in the microvasculature, with 1 mu M FM LP resulted in a Delta PAP(max) = 8.4 +/- 1.1 torr (t = 3.7 +/- 0.19 m in) and a twofold increase in K-f,K-c/Delta W (t = 60 min) that were a ccompanied by a myeloperoxidase (MPO)-release (MPOmax = 56.1 +/- 7.3 m U/l, after 1 to 3 min). There was a strong correlation between Delta P AP(max) and MPOmax (r = 0.97, p < 0.01). Both models of neutrophil-der ived oxidative stress evoked changes in pulmonary circulation providin g evidence for an involvement of PMN via their major oxidant HOCl in p ulmonary hypertension and edema during ARDS.