thromboxane-b2 and Asphyxia-Neonatorum

Hemostatic disturbances are common in asphyxiated newborns after resuscitation. We compared platelet function in hypoxic newborn piglets reoxygenated with 21% or 100% oxygen. Piglets (1-3 d, 1.5-2.1 kg) were anesthetized and acutely instrumented for hemodynamic monitoring. After stabilization, normocapnic hypoxia was induced with an inspired oxygen concentration of 10-15% for 2 h. Piglets were then resuscitated for 1 h with 21% or 100% oxygen, followed by 3 h with 21% oxygen. Platelet counts and collagen (2, 5, and 10 microg/mL)-stimulated whole blood aggregation were studied before hypoxia and at 4 h of post-hypoxia/reoxygenation. Platelet function was studied using transmission electron microscopy and by measuring plasma thromboxane B2 (TxB2) and matrix metalloproteinase (MMP)-2 and -9 levels. Control piglets were sham-operated without hypoxia/reoxygenation. The hypoxemic (PaO2 33 mm Hg) piglets developed hypotension with metabolic acidosis (pH 7.02-7.05). Upon reoxygenation, piglets recovered and blood gases gradually normalized. At 4 h reoxygenation, platelet aggregation ex vivo was impaired as evidenced by a rightward-downward shifting of the concentration-response curves. Electron microscopy showed features of platelet activation. Plasma MMP-9 but not MMP-2 activity significantly increased. Resuscitation with 100% but not 21% oxygen increased plasma TxB2 levels. Platelet counts decreased after hypoxia/reoxygenation but were not different between groups during the experiment. Resuscitation of hypoxic newborn piglets caused platelet activation with significant deterioration of platelet aggregation ex vivo and increased plasma MMP-9 levels. High oxygen concentrations may aggravate the activation of prostaglandin-thromboxane mechanistic pathway.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Blood Platelets; Disease Models, Animal; Humans; In Vitro Techniques; Infant, Newborn; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Microscopy, Electron; Oxygen; Platelet Activation; Platelet Aggregation; Platelet Count; Resuscitation; Sus scrofa; Thromboxane B2

To evaluate the changes of 3', 5'-cyclic adenosine monophosphate (cAMP), thromboxane A2(TXA2) and prostacyclin (PGI2) in cerebrospinal fluid (CSF) in the asphyxiated newborn and explore their roles in hypoxic-ischemic brain damage (HIBD). Thirty-six full term newborns were divided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13 with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB2 (TXA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite) in CSF and plasma were measured 36-72 h after birth by RIA, and the concentrations were expressed as nM/L (cAMP), ng/L(TXB2 and 6-keto-PGF1 alpha). The infants were followed-up at 6 and 12 month of age and Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using Bayley Scales of Infant Development (BSID). The CSF cAMP level in moderate-severe HIE group was 8.60 +/- 2.40, significantly lower than that of the mild HIE group (14.83 +/- 2.84) and the control group (24.43 +/- 2.39) (for both P < 0.01). The levels of TXB2 and 6-keto-PGF1 alpha in CFS in the moderate-severe HIE group (206.06 +/- 29.74, 168.47 +/- 23.02, respectively) were significantly higher than in the mild HIE group (83.37 +/- 28.57, 131.42 +/- 16.57, respectively, P < 0.01) and the control group (41.77 +/- 21.58, 86.23 +/- 13.05, respectively, P < 0.01). The level changes of cAMP, TXB2 and 6-keto-PGF1 alpha in plasma in all groups were similar to those in CSF, but no significant difference was found between mild HIE group and the control group (P > 0.05). The follow-up results showed that MDI and PDI of the moderate-severe HIE group were the lowest (84.79 +/- 13.34, 83.50 +/- 13.28, respectively), followed by mild HIE group (102.19 +/- 7.02, 99.94 +/- 9.08, respectively), with the control group being the highest (116.63 +/- 12.08, 116.69 +/- 10.87, respectively). Univariate analysis showed some significant difference (the moderate-severe HIE group vs. the mild HIE group or the control group, P < 0.01; the mild HIE group vs. the control group P < 0.05). The results suggested that the concentration of cAMP, TXA2 and T/K ratio in CSF after neonatal asphyxia might be sensitive markers in evaluating the severity of brain damage in early stage and predicting the future outcome.

Topics: 6-Ketoprostaglandin F1 alpha; Asphyxia Neonatorum; Biomarkers; Cyclic AMP; Epoprostenol; Female; Follow-Up Studies; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Male; Thromboxane A2; Thromboxane B2

Blood plasma thromboxane-B2 (TXB2) and 6-keto-PGF1 alpha levels were determined by radioimmunoassay technique during the first six to sixteen hours of life in 16 newborn infants with severe asphyxia, 18 newborn infants with mild asphyxia and 27 normal term neonates. Plasma lipid peroxidation (LPO) content was measured by TBA-colour-contrast method in 15 infants with severe asphyxia, 17 infants with mild asphyxia and 24 healthy term newborn infants. The results showed that blood plasma LPO, TXB2 and 6-keto-PGF1 alpha levels in infants suffering from severe asphyxia were higher than those in infants with mild asphyxia and normal infants (P < 0.01), but no significant difference was noted between the mild asphyxia group and normal control group (P > 0.01). These suggest that production of free radicals is increased and prostaglandin metabolism is triggered in the infants with severe asphyxia, that cerebral ischemia and hypoxia caused by asphyxia contributes to the augmented production of prostaglandins and free radicals, and that accumulation of free radicals and prostaglandin enhances brain damage and the metabolism of arachidonic acid appears to be an important source of the free radicals in infants with intrauterine asphyxia.

Topics: 6-Ketoprostaglandin F1 alpha; Asphyxia Neonatorum; Female; Free Radicals; Humans; Infant, Newborn; Lipid Peroxides; Male; Prostaglandins; Radioimmunoassay; Thromboxane B2

Lumbar CSF eicosanoids were measured in 11 neonates with perinatal asphyxia and 12 neonates with suspected sepsis. In the asphyxia group low levels of thromboxane B2 and prostaglandin F2a were detected in five neonates, all of which had had a lumbar puncture prior to 4 hours of age. In the group with suspected sepsis two infants had positive blood cultures and one had strep meningitis. CSF eicosanoids were nondetectable in all patients in this second group with the exception of the infant with meningitis. With meningitis CSF eicosanoids were markedly elevated. These findings suggest that lumbar CSF eicosanoids do not appear to be a clinically useful tool. The data further suggest that eicosanoids are involved in the inflammatory response to meningitis.

Topics: Asphyxia Neonatorum; Dinoprost; Eicosanoic Acids; Humans; Infant, Newborn; Lumbosacral Region; Radioimmunoassay; Sepsis; Thromboxane B2

To study the production of proaggregatory thromboxane A2 (TxA2) by fetal and neonatal platelets, blood specimens were collected from umbilical cords immediately after delivery at term (n = 22), from newborn infants during the first 10 days of life (n = 85), from infants between 1 and 3 months of age (n = 14), and from healthy adults (n = 18). The blood samples were allowed to clot spontaneously at +37 degrees C for 60 min, and the concentrations of thromboxane B2 (TxB2), a stable metabolite of TxA2, in the sera were measured by radioimmunoassay and expressed as nanograms of TxB2/10(6) platelets. Platelet TxB2 generation in term infants at the age of 1 day (1.344 +/- 0.253 ng/10(6) platelets, mean +/- SE, n = 9) was higher than that in cord blood (0.634 +/- 0.042 ng/10(6) platelets, n = 22), or in infants of 1-3 months of age (0.881 +/- 0.099 ng/10(6) platelets, n = 14), or in adults (0.869 +/- 0.062 ng/10(6) platelets, n = 18). Increase in TxB2 generation following birth was seen already at the age of 1 h (1.076 +/- 0.114 ng/10(6) platelets, n = 9). TxB2 synthesis in preterm infants (1.032 +/- 0.136 ng/10(6) platelets, n = 10) did not differ from that in term infants on the 1st day of life, and idiopathic respiratory distress syndrome had no effect on it (1.029 +/- 0.079 ng/10(6) platelets, n = 19). Severe birth asphyxia was accompanied by reduced TxB2 formation (0.564 +/- 0.201 ng/10(6) platelets, n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Asphyxia Neonatorum; Blood Platelets; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Male; Respiratory Distress Syndrome, Newborn; Thromboxane B2; Thromboxanes