Abstract
ABSTRACT: Neonatal group B streptococcal (GBS) sepsis produces pulmonary arterial hypertension and hypoxemia that are preventable by pretreatment with the selective thromboxane A2 synthase inhibitor, dazmegrel. In the present experiment we administered dazmegrel (8 mg/kg) 2 h after the initiation of a 2½ h infusion of 5 × 108 GBS/kg/h in ten 2− to 3-wk-old piglets. The multiple inert gas elimination technique was used to measure intrapulmonary shunt and alveolar ventilation to pulmonary perfusion mismatching. Thromboxane B2, the stable metabolite of thromboxane A2, and 6-keto-prostaglandin F1α, the stable metabolite of prostacyclin, were assayed in arterial blood. Pulmonary arterial pressure increased immediately after initiation of the GBS infusion, rising from 12 ± 2 to 34 ± 4 torr (p < 0.02); pulmonary vascular resistance increased by 400% (p < 0.01). Arterial hypoxemia developed (p < 0.02) in association with an increase in the low ventilation-perfusion ratio index but without a significant increase in intrapulmonary shunt. Thromboxane B2 levels increased 10-fold. Infusion of the carrier substance for dazmegrel after 2 h of GBS infusion produced no change in any variables. In contrast, infusion of the drug resulted in the return to pre-GBS infusion baseline values for both pulmonary arterial pressure and pulmonary vascular resistance. However, no improvement in arterial pO2 or in the low ventilation-perfusion ratio index occurred. Both pulmonary vascular resistance and pulmonary arterial pressure remained normal for 0.5 h after dazmegrel administration despite continued GBS infusion. Thromboxane B2 levels were decreased 30 min after dazmegrel (p < 0.02), but remained greater than pre-GBS levels. Dazmegrel reversed pulmonary hypertension and elevated pulmonary vascular resistance, but did so without concomitant improvement in pulmonary gas exchange, when administered after 2 h of GBS infusion.
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Truog, W., Gibson, R., Juul, S. et al. Neonatal Group B Streptococcal Sepsis: Effects of Late Treatment with Dazmegrel. Pediatr Res 23, 352–356 (1988). https://doi.org/10.1203/00006450-198804000-00003
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DOI: https://doi.org/10.1203/00006450-198804000-00003