6-ketoprostaglandin-f1-alpha and Streptococcal-Infections

Capsular type-specific polysaccharide is thought to be an important pathogenetic factor in Group B streptococcus (GBS) sepsis. To determine the effects of capsular type-specific polysaccharide on GBS-induced hemodynamic responses, anesthetized infant piglets were infused for 3 h with three related GBS Type lb strains that express different amounts of capsular type-specific polysaccharide. A larger capsule strain and a smaller capsule strain were isolated from an infected infant and its mother, respectively. A capsule-deficient mutant was then made from the larger capsule strain by transposon insertion mutagenesis. The smaller capsule strain and capsule-deficient mutant caused similar elevations in mean pulmonary artery pressure and pulmonary vascular resistance index and reductions in cardiac index. The larger capsule strain caused moderate pulmonary hypertension, but this response was smaller than for the other two GBS strains. Further comparisons in responses between the large capsule strain and its capsule-deficient mutant were then performed using unanesthetized piglets. The mutant caused significantly greater pulmonary hypertension and arterial plasma thromboxane B2 levels than the large capsule strain. The pulmonary hypertension induced by both strains was reversed by dazmegrel, a thromboxane A2 synthase inhibitor. These results suggest that (1) capsular type-specific polysaccharide is not an essential component in the generation of acute hemodynamic responses; (2) expression of large amounts of capsular type-specific polysaccharide on the organism surface partially inhibits GBS-induced pulmonary hypertension; and (3) the inhibition of the pulmonary responses is due to reduced thromboxane A2 release.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Analysis of Variance; Animals; Bacterial Capsules; Disease Models, Animal; Drug Evaluation, Preclinical; Hemodynamics; Hypertension, Pulmonary; Imidazoles; Polysaccharides, Bacterial; Streptococcal Infections; Streptococcus agalactiae; Swine; Thromboxane B2; Thromboxane-A Synthase

Prostacyclin is released during hyperventilation (HV); however, its role as mediator of HV-induced pulmonary vasodilation remains controversial. We have investigated this by studying the effects of HV on pulmonary artery pressure (PAP) in otherwise normal lungs versus lungs vasoconstricted with group B streptococci (GBS), with and without prior prostacyclin synthesis inhibition. Two- to 3-wk-old piglets were given tranylcypromine, a prostacyclin synthetase inhibitor (n = 6), or placebo (n = 6). Animals were mechanically ventilated normally, then hyperventilated (PCO2 1.5 +/- 0.2 kPa) and then returned to normal ventilation. After each 30-min segment, plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (prostacyclin hydrolysis product) levels and PAP were measured. Then GBS infusions were administered to both groups to induce pulmonary hypertension. With GBS, the normal ventilation/hyperventilation/normal ventilation protocol was repeated as above.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Epoprostenol; Hypertension, Pulmonary; Hyperventilation; Lung; Pulmonary Artery; Streptococcal Infections; Streptococcus agalactiae; Swine; Vasodilation

In a common bile duct contamination model, we studied the effect of Streptococcus faecalis compared with Escherichia coli in sheep with chronic lymph fistulas to investigate the role of enterococcus in acute lung injury and acute sepsis. Early pulmonary hypertension in the E coli group was not expressed in the S faecalis group, probably due to a failure of S faecalis to illicit a thromboxane A2 response. In the late period, E coli was associated with significantly greater lung microvascular damage compared with S faecalis. The lack of difference between groups with respect to complement activation suggests the action of chemotactic factors, in addition to complement, mediating granulocyte aggregation, and neutropenia. In this model, S faecalis demonstrated limited pathogenicity as expressed in lung microvascular injury compared with E coli.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Cardiac Output; Enterococcus faecalis; Escherichia coli Infections; Hematocrit; Leukocyte Count; Lung; Lymphatic System; Pulmonary Artery; Pulmonary Circulation; Pulmonary Wedge Pressure; Sheep; Streptococcal Infections; Thromboxane B2

In order to evaluate the role of leukotrienes in group B streptococcal (GBS) sepsis we studied the effect of a leukotriene receptor antagonist, FPL 57231, on the late hemodynamic changes occurring secondary to an infusion of live GBS. Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5 x 10(7) org/kg/min) while systemic arterial (Psa) and pulmonary artery pressures (Ppa) were measured. To separate the effects of the lipoxygenase products of arachidonic acid from those of the cyclooxygenase by-products, animals in control and treatment groups received indomethacin, a cyclooxygenase blocking agent, 15 min after the infusion of GBS was begun. In addition to GBS and indomethacin, treatment animals received a 30 min infusion of FPL 57231 starting 120 min after the bacterial infusion was begun. All study animals responded to bacteria within 15 min with marked elevation in pulmonary artery pressure (X +/- SD) (12 +/- 3 to 49 +/- 5 mmHg; p less than .01), and a decline in PaO2 (84 +/- 9 to 49 +/- 5 mmHg; p less than .01) and cardiac output (0.29 +/- 0.04 to 0.18 +/- .07 liter/min/kg; p less than .01). These changes were reversed by indomethacin. Subsequent values remained relatively stable until approximately 90 min when a gradual decrease in cardiac output (CO) and PaO2, and an increase in Ppa, and calculated systemic (SVR) and pulmonary (PVR) vascular resistances occurred. After the initial increase in TxB2 and 6-keto-PGF1 alpha, indomethacin treatment resulted in return of these values to baseline with no further increase throughout the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Chromones; Hemodynamics; Hydrogen-Ion Concentration; Pulmonary Wedge Pressure; Sepsis; Streptococcal Infections; Streptococcus agalactiae; Swine; Thromboxane B2

13 newborn piglets with group-B-beta-hemolytic-streptococci (GBS)-induced pulmonary hypertension were assigned to receive either placebo (group 1) or Dazmegrel, a thromboxane synthetase inhibitor (group 2). All piglets with pulmonary hypertension had increased thromboxane B2 (TxB2) and 6-keto PGF1 alpha levels. With continued GBS infusion, the placebo group demonstrated a continued elevation of pulmonary artery pressure (PAP) and of TxB2. The Dazmegrel piglets, however, despite continued GBS infusion, demonstrated a selective decrease in PAP associated with a significant decrease in TxB2 levels and stability of systemic pressure and cardiac output. These data demonstrate that thromboxane synthetase inhibition is effective therapeutically in selectively reducing PAP.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Epoprostenol; Hypertension, Pulmonary; Imidazoles; Radioimmunoassay; Streptococcal Infections; Swine; Thromboxane B2; Thromboxane-A Synthase

A rabbit model of group B Streptococcal (GBS) shock was used to study the effects of prostaglandin synthetase inhibition on the hemodynamic and hematologic response to GBS shock. The infusion of heat-killed GBS in groups I and II produced significant decreases in mean arterial pressure, neutrophil counts, and platelet counts (p less than 0.05), and significant rises in concentrations of thromboxane B2 and 6-Keto-PGF1 alpha, the stable metabolites of thromboxane A2 and prostacyclin (p less than 0.05). Administration of indomethacin (4 mg/kg) after GBS infusion (group II) was associated with a significant rise in mean arterial pressure and a significant decline in thromboxane B2 and 6-Keto-PGF1 alpha concentrations (p less than 0.05) but had no effect on GBS-induced hematologic alterations. Indomethacin administration before GBS infusion (group III) prevented alterations in mean arterial pressure and was associated with a decrease in thromboxane B2 and 6-Keto-PGF1 alpha concentrations. Indomethacin in group III did not prevent neutropenia and thrombocytopenia and may have exacerbated neutropenia. Alteration of experimental GBS shock with prostaglandin synthetase inhibition produces disparate hemodynamic and hematologic response.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bicarbonates; Blood Gas Analysis; Blood Platelets; Blood Pressure; Cyclooxygenase Inhibitors; Disease Models, Animal; Humans; Indomethacin; Infant; Leukocyte Count; Neutrophils; Platelet Count; Rabbits; Shock, Septic; Streptococcal Infections; Streptococcus agalactiae; Thromboxane B2

The role of thromboxane (Tx) A2 in Streptococcus pneumoniae-induced granulocytopenia, thrombocytopenia, and pulmonary leukostasis is unclear. Rabbits were injected with 0.85% NaCl, nonviable pneumococci, or nonviable pneumococci after pretreatment with TxA2 synthetase inhibition. Blood was obtained immediately before and at times after injection for granulocyte and platelet counts and assays of TxB2 and 6-keto prostaglandin F1 alpha (6-ketoPGF1 alpha). Animals were evaluated for pulmonary leukostasis histologically and biochemically (myeloperoxidase activity). Pneumococcal challenge induced significant granulocytopenia (P less than .001), thrombocytopenia (P less than .001), and elevations in levels of both TxB2 (P less than .05) and 6-ketoPGF1 alpha (P less than .001) as well as pulmonary leukostasis (P less than .001). TxA2 synthetase inhibition blocked the pneumococcus-induced elevation in level of TxB2 without significantly altering levels of circulating granulocytes, platelets, or 6-ketoPGF1 alpha. Pulmonary leukostasis was not blocked. In another group of pneumococcus-challenged animals, no significant transpulmonary gradients of either TxB2 or 6-ketoPGF1 alpha were found.

Topics: 6-Ketoprostaglandin F1 alpha; Agranulocytosis; Animals; Epoprostenol; Lung; Methacrylates; Rabbits; Streptococcal Infections; Thrombocytopenia; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

In order to evaluate the influence of leukotrienes on group B streptococcal (GBS) sepsis we studied the effect of a leukotriene antagonist, FPL 57231, on the early hemodynamic changes occurring secondary to an infusion of live GBS. Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5 X 10(8) org/kg/min) while systemic arterial pressure and pulmonary artery pressure were measured continuously. Cardiac output was measured by thermodilution; and plasma samples for determination of thromboxane B2 and 6-keto-PGF1 alpha were taken at preset intervals. In addition to GBS, treatment animals received a continuous infusion of FPL 57231 starting 15 min after the bacterial infusion was begun. Study animals as a whole responded to bacteria within 15 min with a marked elevation in pulmonary artery pressure from 13.6 +/- 4 to 44.6 +/- 6 mm Hg (p less than 0.001), and a decline in PaO2 (79 +/- 9 to 44 +/- 5 mm Hg) (p less than 0.001) and a cardiac output (0.27 +/- 0.07 to 0.15 +/- 0.06 liter/min/kg) (p less than 0.0001). In animals treated with FPL 57231 these changes were reversed or significantly attenuated by 60 min. In the control group pH deteriorated significantly to 7.17 +/- 0.1 compared to baseline values (p less than 0.01) by 60 min, while treatment group animals maintained a pH of 7.3 +/- 0.23. Thromboxane B2 and 6-keto PGF1 alpha were similar in both groups and did not change during the study period. In addition, survival was significantly longer in treatment (191 +/- 44 min) compared to control animals (100 +/- 32 min) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Cardiac Output; Chromones; Hemodynamics; Pulmonary Artery; Sepsis; Streptococcal Infections; Streptococcus agalactiae; Swine; Thromboxane B2

Seventeen piglets were infected with a continuous intravenous infusion of live group B beta-hemolytic streptococci (GBS). Hemodynamic changes were recorded, and blood samples were drawn for measurement of thromboxane B2 (TxB2) (stable metabolite of thromboxane A2) and 6-keto-PGF1 alpha (stable metabolite of prostacyclin). Control animals (n = 9) received only bacteria, while treatment animals (n = 8) received indomethacin, 3 mg/kg IV, 15 min after the start of the bacterial infusion. Control animals responded to the bacteria within 15 min with marked elevation in mean pulmonary artery pressure (Ppa) from 15 +/- 8 to 39 +/- 6 mm Hg and decline in PaO2 from 80 +/- 11 to 51 +/- 6 mm Hg and cardiac output (CO) from 0.24 +/- 0.07 to 0.13 +/- 0.07 liters/min/kg. Mean arterial blood pressure (AoP) significantly decreased from baseline value of 95 +/- 13 to 51 +/- 32 mm Hg by 180 min. In animals treated with indomethacin, these changes were reversed or significantly attenuated. The hemodynamic changes were associated temporally with elevations in plasma concentrations of TxB2 or 6-keto-PGF1 alpha. In the first 60 min, TxB2 levels in both groups correlated with Ppa (r = 0.72, p less than 0.001) and PaO2 (r = -0.60, p less than 0.001). A strong negative correlation between TxB2 and CO was observed over the first 180 min (r = -0.73, p less than 0.001). There was a statistically significant correlation between AoP and 6-keto-PGF1 alpha concentration between 60 and 180 min (r = -0.54, p less than 0.002). Indomethacin improved the hemodynamic function in this model of GBS sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Cardiac Output; Epoprostenol; Hemodynamics; Indomethacin; Streptococcal Infections; Streptococcus agalactiae; Swine; Thromboxane A2; Thromboxane B2; Thromboxanes; Time Factors