ABSTRACI'. The lung appears to be one of the dominant sites of bacterial clearance from the blood of infant piglets. Part of the lung bacterial clearance involves activation of an oxygen radical bactericidal mechanism that may be central to induction of acute pulmonary hypertension. The present study determined whether this bactericidal activity was intrinsic to resident lung cells. Isolated piglet lung preparations perfused with blood-free salt solution were used to delineate the amount of group B streptococci (GBS) extracted and killed upon transit through pulmonary vasculature. Approximately 45% of infused GBS was deposited in the lung during a single pulmonary transit, whereas nearly 40% of the organisms sequestered in the lung were killed within a 30-min period. Pretreatment with dimethylthiourea, a scavenger of hydroxyl radical that inhibits GBS-induced pulmonary hypertension, attenuated both bacterial uptake and killing to similar extents. Along with its deposition in the lung, GBS also induced concentrationdependent increases in total pulmonary resistance, which were related principally to increases in upstream arterial resistance. Lung weight also increased in a concentrationdependent manner. Both the increase in total pulmonary resistance and lung weight were temporally related to elevation in perfusion medium content of the stable thromboxane degradation product, thromboxane B2. Pretreatment with indomethacin, a prostaglandin H synthase inhibitor, or sodium(E)-3[4-(1-imidazolyl-methyl)phenyl]-2-propenoic acid a thromboxane synthase inhibitor, reduced GBS-induced pulmonary hypertension and edema. Infusion of thromboxane mimetic, 9,ll-dideoxy-9a,l la-epoxymethano prostaglandin F2a, mimicked the ability of GBS to increase total pulmonary and upstream arterial resistances but not development of pulmonary edema. These results suggest that, in isolated piglet lungs, GBS evokes an intrinsic bactericidal response residing within lung cells, probably pulmonary intravascular macrophages, which may be responsible for the initiation of pulmonary hemodynamic changes. It also appears that oxygen radicals play a major role in the bactericidal mechanism directed against G B S In addition, these results suggest that thrombixane mav be the maior arachidonic acid metabolite responsible for*G~~-inducid pulmonary hypertension but perhaps not for development of pulmonary edema.
(E)-314-(1-imidazolyl-methyl)phenyl]-2-propenoic acid HBSS, Hanks' balanced salt solution U44069, 9,ll-dideoxy-9a,l la-epoxymethano prostaglandin F2aA serious complication of neonatal GBS infection is pulmonary hypertension (1, 2). Although studies in animal models of GBS sepsis have incriminated various chemical mediators in the pulmonary hypertensive response, including TXA2 (3), leukotrienes (4), toxic oxygen radicals ( 5 ) , and tumor necrosis factor (6), much remains to be learned regarding the pathogenesis of lung injury in this setting. For example, the specific mechanism whereby bacteria trigger elaboration of vasoactive mediators has yet t...