HEPARIN IMPROVES GAS-EXCHANGE DURING EXPERIMENTAL ACUTE LUNG INJURY IN NEWBORN PIGLETS

Although intrapulmonary fibrin deposition is a pathognomonic feature o f acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both hepari n and antithrombin (AT) concentrate improve gas exchange during experi mental respiratory distress syndrome. We also tested whether combinati on therapy is more beneficial than monotherapy. Forty-eight newborn pi glets were randomized within 12 litters to one of four groups in a fac torial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechani cal ventilation was continued for 24 h during which ventilator pressur es and inspired oxygen were adjusted to maintain normal blood gases. T he arterial/alveolar oxygen tension ratio (a/A ratio) and the ventilat or efficiency index (VEI) at 18 and 24 h were compared by repeated mea sures analysis of variance (ANOVA). In contrast to our hypothesis, onl y heparin improved gas exchange, and we found little evidence of an in teraction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in th e presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. C orresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hya line membrane formation was also decreased in heparin-treated animals (p = 0.02).