Intrapulmonary application of a 5‐lipoxygenase inhibitor using surfactant as a carrier reduces lung edema in a piglet model of airway lavage

Leukotriene‐generated effects on microvascular integrity and polymorphonuclear leukocytes (PMNL) play a key role in the inflammatory process of the alveolar‐capillary unit in neonatal acute respiratory distress syndrome. We asked if intrapulmonary application of MK886, a 5‐lipoxygenase inhibitor, and the use of a porcine surfactant preparation (Curosurf™) as a carrier substance would improve lung function in a neonatal piglet model of airway lavage. Anesthetized, mechanically ventilated newborn piglets (n = 19) underwent repeated airway lavage to induce acute lung injury. Piglets then received either surfactant alone (S, n = 6), or MK886 admixed with surfactant (S + MK, n = 7), or an air‐bolus injection as control (C, n = 6). Measurements of gas exchange, lung function, extravascular lung water (EVLW), cell counts, and leukotriene B 4 (LTB 4 ) concentrations in bronchoalveolar lavage fluid (BAL) were performed during 6 hr of mechanical ventilation. Arterial oxygen partial pressure (PaO 2 ) (S, 13.8 ± 4.2 kPa, vs. S + MK, 20 ± 6.6; P  < 0.05), functional residual capacity (S, 15.1 ± 6.8 ml/kg, vs. S + MK, 18.8 ± 3.7 ml/kg; P  < 0.05), and EVLW (S, 29 ± 14 ml/kg, vs. S + MK 24 ± 4 ml/kg; P  < 0.05) were significantly improved in the MK886 group. This clinical effect was linked with a decrease in LTB 4 concentration in BAL (S, 3.5 (1.9–5.4) pg/ml, vs. S + MK, 1.6 (0.7–4.7) pg/ml; P  < 0.05) and an increase in IL‐8 (S, 2,103 (852–4,243) pg/ml, vs. S + MK, 3,815 (940–26,187) pg/ml; P  < 0.05). PMNL counts in BAL were reduced (S, 570 ± 42 cells/ml, vs. 275 ± 35 cells/ml; P  < 0.05). In conclusion, intrapulmonary application of the 5‐lipoxygenase inhibitor MK886 with surfactant as a carrier improves lung function by decreasing EVLW as the main response to LTB 4 reduction. Pediatr Pulmonol. 2006; 41:452–462. © 2006 Wiley‐Liss, Inc.