Evidence for hydroxyl radical involvement in group B streptococcus-induced pulmonary hypertension and arterial hypoxemia in young piglets.
Early onset neonatal GBS infection is associated with pulmonary hypertension, pulmonary edema, and arterial hypoxemia. Although the mechanisms underlying these cardiopulmonary disturbances are not completely understood, multiple lines of evidence suggest that inflammatory mediators may be involved. This study examined the actions of dimethylthiourea (DMTU), a relatively selective scavenger of hydroxyl radical, on GBS-induced pulmonary hypertension, arterial hypoxemia, and pulmonary edema formation in young piglets. Relative to control animals, intravenous infusion of GBS (10(8) organisms/kg/min for 60 min) provoked sustained increases in pulmonary arterial pressure (Ppa: +88%) and total pulmonary resistance (TPR: 128%). GBS infusion also was associated with profound decreases in arterial PO2 (-58%). Pulmonary edema was present in GBS-treated animals as evidenced by an 8.4% increase in the lung wet-to-dry weight ratio. After pretreatment with DMTU (0.75 g/kg administered intravenously over 30 min), GBS increased Ppa by 33% and TPR by only 16%. Similarly, after DMTU pretreatment GBS decreased arterial oxygen tension by only 12%. DMTU also limited the GBS-induced increase in lung wet-to-dry weight ratio to 2.6%. These findings demonstrate that DMTU attenuates GBS-induced pulmonary hypertension, pulmonary edema, and arterial hypoxemia and suggest that hydroxyl radicals play an important role in these cardiopulmonary disturbances.
Pauly
T H
TH
University of Kentucky A.B. Chandler Medical Center, College of Medicine, Department of Pediatrics, Lexington 40536.
Bowdy
B D
BD
Haven
C A
CA
Barr
S B
SB
Gillespie
M N
MN
D000818:Animals; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology*; D000860:Hypoxia / Q000188:drug therapy / Q000209:etiology*; D011654:Pulmonary Edema / Q000188:drug therapy / Q000209:etiology; D013290:Streptococcal Infections / Q000188:drug therapy*; D013292:Streptococcus agalactiae; D013552:Swine; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; C038983:1,3-dimethylthiourea; D013890:Thiourea