6-ketoprostaglandin-f1-alpha and Asphyxia-Neonatorum

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

Decreased fetoplacental prostacyclin (PGI2) production has been shown in preeclampsia, and increased pulmonary PGI2 synthesis has been demonstrated in experimental hypoxia. We measured the urinary excretion of the main metabolites of PGI2, 6-keto-prostaglandin F1 alpha (6-keto) and 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3-dinor), during the first day of life in infants born to mothers with preeclampsia (n = 26), in infants with birth asphyxia (n = 12), and in control infants (n = 14). The mean excretion of 6-keto in control infants increased from 9.3 to 14.3 ng/h/1.73 m2 from 0-12 to 12-24 h of age, and a corresponding change from 3.5 to 7.0 ng/h/1.73 m2 was seen in 2,3-dinor excretion. In infants of preeclamptic mothers the excretion values at 0-12 and 12-24 h and the pattern of change were not significantly different from controls. In asphyxiated infants, the mean excretion values at 0-12 and 12-24 h of 6-keto (11.0 and 11.6 ng/h/1.73 m2) and 2,3-dinor (6.0 and 5.8 ng/h/1.73 m2) were not significantly different from control infants, but no increase was seen. We conclude that PGI2 production in infants of preeclamptic mothers is not impaired, but after perinatal asphyxia there is an altered pattern of PGI2 metabolite excretion, suggesting decreased production capacity.

Topics: 6-Ketoprostaglandin F1 alpha; Asphyxia Neonatorum; Creatinine; Epoprostenol; Female; Humans; Infant, Newborn; Kidney; Male; Pre-Eclampsia; Pregnancy