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.