Antenatal glucocorticoids attenuate activation of the inflammatory reaction and clotting in preterm lambs.
Recently we have shown that activation of inflammatory reaction and clotting can be found immediately after delivery in preterm lambs ventilated for respiratory distress syndrome (RDS). To investigate whether antenatal glucocorticoids would attenuate postnatal activation of the inflammatory reaction and clotting, we studied ventilated preterm lambs delivered by cesarean section, 24 h after antenatal administration of betamethasone or placebo. Blood was sampled before clamping the cord, 5, 10, and 15 min after delivery, and 2-hourly afterwards. Blood was used to determine oxygenation index, alveolar - arterial partial O(2) difference (AaDO(2)), AP50 titer (see text), polymorphonuclear leukocytes (PMNs), beta-glucuronidase, thrombin inhibition, activated partial thromboplastin time, and clot lysis time. Bronchoalveolar lavage fluid was sampled before clamping the cord and 30 min and 1, 2, 4, 6 and 8 h after delivery and was analyzed for elastase, thrombin, and protein. After removal of the lungs, static compliance and water content of the lungs were determined. We found that betamethasone-treated lambs had lower oxygenation index and AaDO(2) than controls. At birth, PMN levels were higher, and the beta-glucuronidase level was lower after betamethasone treatment. PMNs and beta-glucuronidase did not change in betamethasone-treated lambs, in contrast to controls. Thrombin inhibition, activated partial thromboplastin time, and clot lysis time did not change in betamethasone-treated lambs, in contrast to controls. In both groups, elastase and protein levels in bronchoalveolar lavage fluid increased; the thrombin level increased in controls. The static compliance was better, and the water content of the lung was lower in the betamethasone-treated lambs. We conclude that early systemic activation of inflammatory reaction and clotting in preterm lambs with RDS are attenuated by antenatal betamethasone administration. Whether this is a direct effect of betamethasone on the inflammatory reaction or a result of a reduced ventilatory support because of less severe RDS after antenatal betamethasone treatment remains to be elucidated.
Jaarsma
Anneke S
AS
Department of Pediatrics, University Hospital Groningen, Groningen, The Netherlands. a.s.jaarsma@bkk.azg.nl
Braaksma
Margriethe A
MA
Geven
Wil B
WB
Van Oeveren
Wim
W
Bambang-Oetomo
Sidarto
S
D000818:Animals; D000831:Animals, Newborn / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001623:Betamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002102:Cadaver; D002585:Cesarean Section; D015633:Extravascular Lung Water / Q000187:drug effects / Q000378:metabolism; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology; D005966:Glucuronidase / Q000097:blood; D007249:Inflammation / Q000517:prevention & control*; D007958:Leukocyte Count; D009504:Neutrophils / Q000473:pathology; D010196:Pancreatic Elastase / Q000378:metabolism; D010314:Partial Thromboplastin Time; D011295:Prenatal Care; D012120:Respiration Disorders / Q000097:blood / Q000378:metabolism / Q000628:therapy; D012121:Respiration, Artificial / Q000009:adverse effects*; D012756:Sheep; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D001623:Betamethasone; D005966:Glucuronidase; D010196:Pancreatic Elastase; D013917:Thrombin