Objectives: Previous studies in adults suggest that various types of physiologic stress appear to decrease phagocytic cell function. Adherence and chemotaxis of, and phagocytosis and bacterial killing by, neonatal neutrophils are altered compared with adult neutrophil function. Stresses encountered by the fetus and neonate, such as asphyxia, were hypothesized to further alter neonatal neutrophil function. To investigate the impact of asphyxia on systemic immunity, we developed a rat model of acute asphyxia and evaluated the effect of asphyxia on neutrophil number and function. Design: Prospective, laboratory study. Setting: Research laboratory. Subjects: Adult female Wistar rats. Interventions: Exposure to CO2 and cold stress. Measurements and Main Results: Arterial blood gas, blood glucose, neutrophil number, neutrophil-mediated, complement-dependent bacterial phagocytosis and killing were determined. After a 20-sec exposure to CO2 and cold stress (dry ice vapors), adult rats developed acute respiratory acidosis (pH 6.89 +/- 0.26, Paco(2) 220 +/- 183 torr [29.3 +/- 24.3 kPa]), and mild hypoxia (60 +/- 20 torr [8.0 +/- 2.7 kPa]) followed by significant metabolic acidosis (base deficit = -12.0 +/- 1.5). Neutrophil number slowly increased and reached statistical significance by 72 hrs (5.0 +/- 1.5 x 10(3)/ mm(3)) compared to controls (2.9 +/- 1.6 x 10(3)/mm(3)) (p =.03). Phagocytosis and killing of group B streptococci by neutrophils isolated immediately after asphyxia were significantly impaired (p =.03), and this decrease in function lasted for 24 hrs after asphyxia (p =.04), as measured by two different in vitro complement and antibody-mediated functional assays. Conclusions: After brief exposure to CO2 and cold stress, rats developed an acute respiratory acidosis and subsequent metabolic acidosis similar to acute asphyxia. Neutrophil number did not increase until 72 hrs after asphyxia. However, neutrophil-mediated phagocytosis and killing of bacteria were immediately impaired. We speculate that asphyxia may increase the risk for sepsis secondary to altered neutrophil function.
