Studies of Short-Term Pulmonary and Peripheral Vascular Responses Induced in Oophorectomized Sheep by the Infusion of a Group B Streptococcal Extract

Abstract

SummaryShort-term (0-30 min) pulmonary and systemic vascular responses of oophorectomized ewes infused intravenously with a trichloroacetic acid (TCA) extract of a type I11 (strain 878) group B streptococci?s (GBS) were studied. TCA-878 extract induced significant pulmonary hypertension, reduction in femoral artery pressure and reduced femoral artery Po2. These responses were similar to those observed after the infusion of sublethal doses of E. coli endotoxin and could be prevented by priming the animal with ibuprofen or indomethacin. Ewes rechallenged 48 h after their initial dose of TCA-878 extract experienced pulmonary arterial pressure significantly higher than those induced by the first infusion. Similar augmented responses were not seen after rechallenge with endotoxin. Larger doses of TCA-878 extract resulted in increasingly higher pulmonary arterial pressure. We conclude that the venous infusion of TCA extracts of GBS-878 induces significant pulmonary hypertension in sheep and that this response may be mediated by prostaglandins. The vasoactive substance extracted from these streptococci could play a role in promoting the vascular instability experienced by the human neonate with early onset GBS disease. Abbreviations FAP, femoral artery pressure GBS, group B streptococci PAP, pulmonary artery pressure PG, prostaglandins SDS-PAGE, sodium dodecyl sulfate-polyacrylamid gel electrophoresis TCA, trichloroacetic acid GBS are common causes of serious infections in the human neonate (1,8). Though the clinical syndromes caused by GBS are well described, little is known of how these organisms induce the attendent physiologic abnormalities. Recently, Hellerqvist, et al. (7) and Rojas et al. (13) reported the isolation of a carbohydrate "exotoxin" from the culture media in which type 111 GBS had been grown. Intravenous infusion of this material was found to induce pulmonary hypertension, fever, and increase pulmonary lymphatic flow in adult sheep. At the time of the Hellerqvist and Rojas reports (7, 13), we were preparing TCA extracts of washed, whole GBS for utilization in studies of GBS antigens. One person in our group (W.F.O.) was utilizing the oophorectomized adult ewe model of Cefalo et al. (2, 3, 11) to examine the early phase of vascular responses in sheep after the venous infusion of E. coli endotoxin. Noting some striking similarities in PAP responses induced by the Rojas' "exotoxin" and E. coli endotoxin, we infused sterile TCA extract of whole GBS (type 111, 878) into an oophorectomized ewe. The infusion resulted in a prompt and impressive rise in PAP, a reduction in FAP, and a drop in femoral artery Po2. Once our studies had excluded endotoxin contamination of whole organism extracts (TCA-878) and produced a predictable vascular response in the available ewe model, we devised studies: 1) to compare the vascular responses induced by TCA-878 extract with those induced by E. coli endotoxin; 2 ) to examine responses to increasing concentrations of TCA-878; 3) to determine whether, as reported with endotoxi...

Group B Streptococcus and E. coli LPS‐induced NO‐dependent hyporesponsiveness to noradrenaline in isolated intrapulmonary arteries of neonatal piglets

“…In addition, two different GBS polysaccharide toxins producing pathophysiological changes mimicking those of GBS infection in neonates have been identified, a non specific mannan polysaccharide (Hellerqvist et al, 1987) and the type III specific capsular polysaccharide (Hemming et al, 1984 The lung is a major target organ in neonatal sepsis . Control values for cNOS and iNOS et al., 1976).…”

A Group B Streptococcal Extract Reduces Neutrophil Counts and Induces Neutrophil Aggregation

“…Several studies demonstrate that sterile cell-free extracts of GBS produce similar effects when infused into lambs and piglets (2,3,6,7). In this study, a TCA extract of GBS strain 878 (type 111) induced reductions in white blood cell counts and a marked accumulation of PMNs in the pulmonary interstitia of newborn lambs.…”

“…Thc typical aggregation-deaggregation curve is seen with GBS-TCA in serum (I). If the GBS-TCA was first exposed to IgG (GBS immune globulin) thc resultant preparation did not cause aggregation (2). Mixing of GBS-TCA with standard Sandoglobulin resulted in augmented irreversible aggregation (3).…”

“…The final extract contained 10% protein, the remainder was carbohydrate including small amounts of group and type I11 carbohydrate as determined by capillary precipitation. Chromatographic carbohydrate fingerprints of the extract resembled those of whole GBS cells (2). A Limulus lysate assay was done to rule out endotoxin contamination of the extract.…”

Thromboxane-Associated Pulmonary Hypertension during Three Types of Gram-Positive Bacteremia in Piglets

“…Some possibilities include 1) different components specific for each organism are capable of inducing pulmonary hypertension, 2) a bacterial component common to all organisms can induce pulmonary hypertension, or 3) a nonspecific circulating particulate/embolic effect is responsible for the physiological changes observed during bacterial infusion in piglets. There are data to support the first contention based on the different structures of E. coli endotoxin compared to two identified GBS polysaccharide "toxins," all of which produce pulmonary hypertension during IV infusion (15,16). Two groups of investigators have identified two different GBS polysaccharide "toxins;" one is derived from the intact organism and apparently related to the GBS type and group specific polysaccharides (1 5), whereas the other is an unrelated mannan polysaccharide derived from GBS culture supernatant (16).…”