title: N-acetylcysteine administration improves platelet aggregation in hypoxia-reoxygenation injury.
abstract: Platelet activation and dysfunction occurs upon hypoxia and reoxygenation and is associated with oxygen free radical generation and matrix metalloproteinase (MMP) -2 and -9 activation. The effect of NAC on platelet function in newborn piglets after asphyxia was studied along with plasma MMP-2 and MMP-9 activities. Piglets (1-4 day, 1.4-2.2 kg) were acutely instrumented for the induction of normocapnic hypoxia (10-15% O2) for 2hr followed by reoxygenation for 1hr with 100% O2 and then 3hr with 21% O2. Animals were randomized to 3 groups (n = 6 each); sham, control and treatment with NAC upon reoxygenation (150 mg/kg i.v. bolus and 100 mg/kg/hr i.v. infusion). Platelet count and collagen (2, 5 and 10 microg/mL)-stimulated whole blood aggregation were studied at baseline and after 4hr reoxygenation. Plasma MMP -2 and -9 activities were analyzed by gelatin zymography. Piglets had severe hypoxia (PaO2 32 +/- 2 vs. 65 +/- 2 mmHg sham; p < 0.05) and metabolic acidosis (pH 6.96 +/- 0.04 vs. 7.33 +/- 0.01 sham; p < 0.05). At 4hr of reoxygenation, platelet counts decreased similarly in all experimental groups, and no animal had a platelet count < 100 x 10(9)/L. Platelet aggregation was significantly reduced with a rightward shift of concentration-response curve. NAC treatment improved platelet aggregatory function at 4hr of reoxygenation (p < 0.05). Plasma MMP-9, but not MMP-2, activities were increased with NAC treatment (147 +/- 19 vs. 51 +/- 20 and 42 +/- 11 AU of control and sham, respectively, p < 0.001). In a newborn piglet model of asphyxia and reoxygenation, NAC treatment effectively improves platelet aggregation when given upon resuscitation.
authors.affiliation: Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Emily
authors.initials: E
authors.lastname: Chan
authors.forename: Laila
authors.initials: L
authors.lastname: Obaid
authors.forename: Scott T
authors.initials: ST
authors.lastname: Johnson
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000860:Hypoxia / Q000097:blood*; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D010100:Oxygen / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D013552:Swine
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010100:Oxygen; D000111:Acetylcysteine