6-ketoprostaglandin-f1-alpha and Bacterial-Infections

Increased mortality from sepsis is associated with high levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha). Linoleic acid, an n-6 essential fatty acid, is the usual precursor of TXB2 and PGF1 alpha, while fish oil is rich in n-3 essential fatty acid, the precursor of less active moieties. Rats were fed chow, an essential fatty acid-deficient diet, or an essential fatty acid-deficient diet supplemented with linoleic acid or fish oil for 2 weeks. The animals then underwent a sham operation or cecal ligation and puncture to induce sepsis. Six hours later, blood was obtained for analysis. The chow and linoleic acid diets produced significant (twofold to fivefold) increases in levels of both TXB2 and PGF1 alpha after sepsis. The essential fatty acid-deficient diet and fish oil diet protected against increases in levels of TXB2 or PGF1 alpha during sepsis. Dietary restriction of linoleic acid or fish oil supplementation may play an important role in altering the inflammatory mediator response to sepsis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bacterial Infections; Cecum; Dietary Fats; Epoprostenol; Fatty Acids, Essential; Fatty Acids, Unsaturated; Fish Oils; Linoleic Acid; Linoleic Acids; Male; Rats; Rats, Inbred Strains; Thromboxane A2; Thromboxane B2

Endogenous formation of thromboxane A2 and prostacyclin were evaluated in seven neonatates with persistent pulmonary hypertension by serial gas chromatographic mass spectrometric determination of their urinary metabolites dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha, respectively. The patients were studied until their hypertension had resolved on clinical criteria. Urinary excretion of dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha was increased when the persistent pulmonary hypertension was associated with group B streptococcal (n = 2) and pneumococcal (n = 1) sepsis. Based on urinary metabolite excretion, endogenous formation of thromboxane A2 and prostacyclin did not consistently differ from normal neonates in four patients with non-septic persistent pulmonary hypertension (hyaline membrane disease (n = 2), asphyxia, and meconium aspiration). These data suggest that thromboxane A2 is not a universal mediator of persistent pulmonary hypertension. It may, however, have a role in the pathophysiology of early onset group B streptococcal disease, and persistent pulmonary hypertension of other infectious aetiology. If these findings are confirmed by further studies, thromboxane synthetase inhibition or receptor antagonism may offer a potential therapeutic approach in neonates with persistent pulmonary hypertension associated with sepsis.

Topics: 6-Ketoprostaglandin F1 alpha; Bacterial Infections; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Thromboxane A2; Thromboxane B2

Renal prostaglandin (PG) production was studied in 32 laparotomized (control) and 33 septic rats (cecal ligation and puncture). Control and septic rats were infused for 18 hr with 5% glucose or 5% glucose and one of three amino acid formulations containing 22, 35, or 45% branched chain amino acids. When comparing renal PG production from endogenous precursors in septic versus control rats, significant increases (P less than 0.01) could be detected for PGE2, 6-keto-PGF1 alpha, and TxB2. The infusion of either 5% glucose alone or 5% glucose with 4.25% of any of the three amino acid formulations tested did not change renal PG production in either control or septic rats.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Amino Acids; Animals; Bacterial Infections; Dinoprostone; Glucose; Kidney; Male; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Thromboxane B2

Acute respiratory failure in humans often follows extrathoracic sepsis. The purpose of this study was to determine the effect of repeated episodes of intra-abdominal sepsis over several weeks on the structure and function of rat lung. Intermittent peritonitis and a bacteremia of Escherichia coli and Bacteroides fragilis were produced by weekly intra-abdominal implants of gelatin capsules containing these organisms (3.0 +/- 1.0 X 10(7) and 5.0 +/- 1.0 X 10(7) colony-forming units/ml, respectively; mean +/- SEM). After 4 weeks alveolar walls were thickened and cellular with focal areas of alveolar space consolidation: circulating polymorphonuclear leukocytes were increased (12.2 +/- 1.2 to 19.9 +/- 2.0 X 10(3)/mm3; p less than 0.05), as were plasma levels of 6-keto-PGF1 alpha (0.56 +/- 0.08 to 1.02 +/- 0.18 ng/ml; p less than 0.01). After 8 weeks the capillary bed was dilated and the alveolar walls and ducts appeared less cellular but showed fibrosis: The WBC count had increased to 25.5 +/- 1.0 X 10(3) (p less than 0.01). After 4 or 8 weeks of intermittent sepsis there was no increase in the pulmonary artery pressure or vascular resistance or any change in arterial oxygen tension, plasma thromboxane beta 2 level, or platelet count. We conclude that repeated bouts of sepsis and bacteremia in the rat cause progressive injury to lung alveoli without evidence of altered blood gas tensions or pulmonary hemodynamics.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Abscess; Animals; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Blood Cell Count; Capsules; Disease Models, Animal; Escherichia coli Infections; Hematocrit; Hemodynamics; Lung; Male; Rats; Rats, Inbred Strains; Respiratory Distress Syndrome; Thromboxane B2