Neonatal group B streptococcal sepsis: effects of late treatment with dazmegrel.
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 2 1/2 h infusion of 5 X 10(8) 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 F1 alpha, 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 less than 0.02); pulmonary vascular resistance increased by 400% (p less than 0.01). Arterial hypoxemia developed (p less than 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 less than 0.02), but remained greater than pre-GBS levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Truog
W E
WE
Department of Pediatrics, University of Washington School of Medicine, Seattle 98195.
Gibson
R L
RL
Juul
S E
SE
Henderson
W R
WR
Redding
G J
GJ
D000818:Animals; D000831:Animals, Newborn / Q000382:microbiology*; D001794:Blood Pressure; D007093:Imidazoles / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D011669:Pulmonary Wedge Pressure; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013290:Streptococcal Infections / Q000188:drug therapy*; D013292:Streptococcus agalactiae; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D013997:Time Factors
D007093:Imidazoles; C039242:dazmegrel; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase