title: Platelet dysfunction in asphyxiated newborn piglets resuscitated with 21% and 100% oxygen.
abstract: Hemostatic disturbances are common in asphyxiated newborns after resuscitation. We compared platelet function in hypoxic newborn piglets reoxygenated with 21% or 100% oxygen. Piglets (1-3 d, 1.5-2.1 kg) were anesthetized and acutely instrumented for hemodynamic monitoring. After stabilization, normocapnic hypoxia was induced with an inspired oxygen concentration of 10-15% for 2 h. Piglets were then resuscitated for 1 h with 21% or 100% oxygen, followed by 3 h with 21% oxygen. Platelet counts and collagen (2, 5, and 10 microg/mL)-stimulated whole blood aggregation were studied before hypoxia and at 4 h of post-hypoxia/reoxygenation. Platelet function was studied using transmission electron microscopy and by measuring plasma thromboxane B2 (TxB2) and matrix metalloproteinase (MMP)-2 and -9 levels. Control piglets were sham-operated without hypoxia/reoxygenation. The hypoxemic (PaO2 33 mm Hg) piglets developed hypotension with metabolic acidosis (pH 7.02-7.05). Upon reoxygenation, piglets recovered and blood gases gradually normalized. At 4 h reoxygenation, platelet aggregation ex vivo was impaired as evidenced by a rightward-downward shifting of the concentration-response curves. Electron microscopy showed features of platelet activation. Plasma MMP-9 but not MMP-2 activity significantly increased. Resuscitation with 100% but not 21% oxygen increased plasma TxB2 levels. Platelet counts decreased after hypoxia/reoxygenation but were not different between groups during the experiment. Resuscitation of hypoxic newborn piglets caused platelet activation with significant deterioration of platelet aggregation ex vivo and increased plasma MMP-9 levels. High oxygen concentrations may aggravate the activation of prostaglandin-thromboxane mechanistic pathway.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2. poyin@ualberta.ca
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Stevens
authors.forename: Erika
authors.initials: E
authors.lastname: Haase
authors.forename: Linda
authors.initials: L
authors.lastname: Stang
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Wei
authors.initials: W
authors.lastname: Etches
authors.forename: Marek W
authors.initials: MW
authors.lastname: Radomski
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000097:blood* / Q000628:therapy*; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008854:Microscopy, Electron; D010100:Oxygen; D015539:Platelet Activation; D010974:Platelet Aggregation; D010976:Platelet Count; D012151:Resuscitation; D034421:Sus scrofa; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D013929:Thromboxane B2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010100:Oxygen