Acute uteroplacental ischemic embryo: lactic acid accumulation and prostaglandin production in the fetal rat brain.
A new experimental model for studying the effects of acute ischemia on brain development in the near-term fetal rat has been devised. Ischemic conditions are achieved by complete clamping of blood vessels branching from the uterine vasculature into each individual fetus for designated times followed by removal of the clamps to permit reperfusion. Accumulation of lactic acid in the fetal brain depends on the length of the restriction period, reaching a plateau level of 29 mumol/g tissue at about 30 min. It also depends on the reperfusion time. Thus after a period of 15 min of restriction lactate levels show an increase over the next 30-min reperfusion to a value of 25.5 mumol/g followed by a rapid decrease to normal values by 3 h of reperfusion. Restriction of 15 min followed by reperfusion of 45 min causes an elevation of prostaglandin E2 (PGE2) level from 12.4 +/- 0.86 ng/g to 21.1 +/- 0.6 ng/g (p less than 0.001). This elevation in PGE2 level is less apparent after 20 min of restriction. No effects are seen on the level of PGF2 alpha. Both PGE2 and PGF2 alpha accumulate in vitro in a time-dependent manner by brain particulate fraction. In vitro synthesis of both PGE2 and PGF2 alpha is inhibited by indomethacin (100% and 68%, respectively) and AA861 (94% and 76%, respectively). BW755c and nordihydroguaiaretic acid do not affect PGE2 formation but enhance PGF2 alpha production by 112% and 152%, respectively. Particulate fractions from restricted brain produce less PGF2 alpha than control brains (6.38 +/- 1.62 versus 11.43 +/- 2.2, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016227:Benzoquinones; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D014599:Uterus / Q000098:blood supply*
D016227:Benzoquinones; D016861:Cyclooxygenase Inhibitors; D007773:Lactates; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D011720:Pyrazoles; D011809:Quinones; D019344:Lactic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin