K. Sandberg et al., THROMBOXANE RECEPTOR BLOCKADE (SQ-29,548) IN GROUP-B STREPTOCOCCAL TOXIN CHALLENGE IN YOUNG LAMBS, Pediatric research, 35(5), 1994, pp. 571-579
Early-onset neonatal group B beta-hemolytic streptococcus (GBS) infect
ion exhibits pathophysiologic characteristics of a toxic shock syndrom
e, in which a cascade of inflammatory mediators are involved. Thrombox
ane A(2) (TXA(2)) is thought to play an important role as a mediator o
f the pulmonary response to GBS toxin, because high lung lymph concent
rations of a TXA(2) metabolite have been observed after GBS toxin inje
ctions in sheep. The aim of this study was to evaluate the effects of
a selective antagonist of the TXA(2)-prostaglandin endoperoxide recept
or (SQ 29,548). Six unanesthetized young lambs, each serving as its ow
n control, were given SQ 29,548 or vehicle control followed by GBS tox
in challenge. Hemodynamic and lung function (lung mechanics, lung volu
me, ventilation) responses were followed for 5 h. When compared with t
he control studies, treatment with SQ 29,548 significantly altered the
response to GBS toxin. SQ 29,548 reduced the increase in pulmonary an
d systemic vascular resistance, improved cardiac output and stroke vol
ume, improved dynamic lung compliance but not airway resistance, and i
mproved oxygenation. The attenuating effect of SQ 29,548 was most pron
ounced during the first phase of toxin response (15-90 min after toxin
infusion), but significant treatment effects were also seen during th
e second phase (120-300 min after toxin infusion). This study demonstr
ates that TXA(2) is an important mediator of the response to GBS toxin
and is responsible for hemodynamic and lung function changes. Thrombo
xane receptor blockade may offer a potential therapeutic approach to i
nfants with severe early-onset GBS sepsis.