Heparin improves gas exchange during experimental acute lung injury in newborn piglets.
Although intrapulmonary fibrin deposition is a pathognomonic feature of acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory distress syndrome. We also tested whether combination therapy is more beneficial than monotherapy. Forty-eight newborn piglets were randomized within 12 litters to one of four groups in a factorial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechanical ventilation was continued for 24 h during which ventilator pressures and inspired oxygen were adjusted to maintain normal blood gases. The arterial/ alveolar oxygen tension ratio (a/A ratio) and the ventilator efficiency index (VEI) at 18 and 24 h were compared by repeated measures analysis of variance (ANOVA). In contrast to our hypothesis, only heparin improved gas exchange, and we found little evidence of an interaction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in the presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. Corresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hyaline membrane formation was also decreased in heparin-treated animals (p = 0.02).
Abubakar
K
K
Departments of Pediatrics, Radiology, Pathology, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Schmidt
B
B
Monkman
S
S
Webber
C
C
deSA
D
D
Roberts
R
R
D000704:Analysis of Variance; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D000990:Antithrombin III / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006818:Hyalin; D008168:Lung / Q000473:pathology; D008297:Male; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood; D011312:Pressure; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011897:Random Allocation; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013552:Swine; D016896:Treatment Outcome; D014692:Ventilation-Perfusion Ratio
D000925:Anticoagulants; D004338:Drug Combinations; D015842:Serine Proteinase Inhibitors; D000990:Antithrombin III; D006493:Heparin; D010100:Oxygen