THROMBOXANE RECEPTOR BLOCKADE (SQ-29,548) IN GROUP-B STREPTOCOCCAL TOXIN CHALLENGE IN YOUNG LAMBS

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.