Group B streptococcal (GBS)
sepsis produces arterial
hypoxemia in newborns. In piglets we previously found that
hypoxemia develops because of increased ventilation perfusion heterogeneity, and reduced mixed venous pO2 occurring in association with decreased pulmonary blood flow. We hypothesize that increased
thromboxane A2 (TxA2) synthesis mediates the immediate alterations in gas exchange found in GBS
sepsis. We studied 18 anesthetized, ventilated piglets before, during, and after a 30-min infusion of 2 X 10(9) colony forming units/kg of GBS. Nine piglets were pretreated with 8 mg/kg of
dazmegrel (DAZ), a TxA2
synthetase inhibitor, and nine animals received GBS without DAZ pretreatment. Pulmonary and systemic arterial pressures, pulmonary vascular resistance, pulmonary blood flow, respiratory gas tensions, intrapulmonary shunt, and SD of pulmonary blood flow, an index of ventilation perfusion mismatching, were measured. Systemic and pulmonary arterial levels of
thromboxane B2 and
6-keto-PGF1 alpha were also measured. The
sham-treated animals showed the expected rise in pulmonary arterial pressure from 12 +/- 3 to 29 +/- 7 torr, (p less than 0.02). By comparison, the animals pretreated with DAZ did not demonstrate
pulmonary arterial hypertension and had a delay in the fall in pulmonary blood flow until 2 h postinfusion. Arterial PO2 did not decline significantly after the GBS infusion in the DAZ-pretreated animals; the untreated animals showed a significant fall in pO2 from baseline. There was no significant change in intrapulmonary shunt or SD of pulmonary blood flow compared to baseline in the DAZ-pretreated animals. The elevation in
thromboxane B2 occurring with GBS
sepsis did not occur in the DAZ-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)