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ABSTRACT. Group B P-hemolytic Streptotocci cause pulmonary hypertension when injected into animals and may precipitate the persistent pulmonary hypertension syndrome in infected human neonates. W e used chronically instrumented piglets to study the effects of repeated injections of heat-killed group B Streptococcus (GBS) type 111. Daily exposure to G B S was associated with a 2-fold or greater potentiation of pulmonary and systemic hypertensive responses after 1 wk. Throughout experimentation, pulmonary pressure changes were more marked than systemic changes. After establishing a dose-response relationship, we chose a control dose that produced intermediate hypertensive responses. W e then evaluated the effects of antibody and various drugs on the hypertensive responses. Preincubation of organisms with rabbit antiserum containing type-specific antibody enhanced the responses. Beta endorphin blockade with naloxone had little or no effect; leukotriene synthesis inhibition also did not affect responses. Both indomethacin, a cyclooxygenase inhibitor, and dazmegrel, a specific thromboxane synthesis inhibitor, blocked the hypertensive responses to GBS. It appears that repeated doses of GBS potentiate the hypertensive responses, a process that we hypothesize may be mediated by development of type-specific antibody a s type-specific antibody levels rose during potentiation. It is likely that thromboxane Az is the effector of the pulmonary and systemic hypertensive responses to GBS injection, because thromboxane inhibition by dazmegrel was a s effective a s indomethacin in blocking these effects. Thromboxane synthesis blockade may prove useful in management of hemodynamic disturbances accompanying severe bacterial infec- It is well known that gram-negative bacterial sepsis and endotoxemia are associated with profound hemodynamic disturbances. More recently, gram-positive bacteria, especially group B Streptococcus, have also been shown to be associated with circulatory disturbances in infected noenates. Clinically these infants may manifest the persistent pulmonary hypertension syndrome wherein continued right-to-left extrapulmonary shunting occurs because of abnormally elevated pulmonary artery pressure and resistance (1,2). Infusions of GBS into experimental animals have been shown to cause marked hemodynamic alterations in the pulmonary and systemic circulations (3-5).We developed a chronically instrumented piglet preparation that permitted repeated injections of heat-killed GBS in conscious animals. We first evaluated the effects of repeated injections of the same organism to test the hypothesis that repeated exposure to GBS was associated with changes in the hypertensive responses. We then attempted to modify the hypertensive responses with immunologic and pharmacologic probes in order to gain insight into the mechanisms underlying these GBSinduced responses. MATERIALS AND METHODSPiglets. Twelve juvenile female piglets weighing 6.8 + 2.1 kg (mean + SD, range 4.4-1 1.8 kg) were anesthetized and mechanically ventilated...

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