Indomethacin reduces ischemia-induced alteration of blood-brain barrier transport in piglets.
Cerebral ischemia-reperfusion (Isc-Rep) alters blood-brain barrier (BBB) transport properties in piglets. Pretreatment with superoxide dismutase and catalase partially attenuates these effects. Activated O2 species produced with Isc-Rep in piglets are generated via prostaglandin (PG) H synthase. This experiment determines if products of PGH synthase alter BBB transport of sodium and albumin. Piglets anesthetized with nitrous oxide and halothane were divided into four groups: 1) control, 2) indomethacin (5 mg/kg iv) with no Isc-Rep, 3) Isc-Rep alone, and 4) Isc-Rep after pretreatment with indomethacin (Indo). Regional transfer coefficients (Kin) and regional cerebral blood flow (microspheres) were measured at 2 h reperfusion after 20 min total global cerebral ischemia. Kin values are represented as absolute values and also relative to blood flow to account for any changes in perfusion caused by ischemia and/or Indo. Indo alone did not alter sodium or albumin transfer compared with control animals. Isc-Rep alone caused a significant increase in sodium and albumin transport compared with all other groups (control cerebral sodium Kin was 18.2 +/- 2.7 cm3.g-1.s-1.10(6) vs. 32.9 +/- 3.1 for Isc-Rep, P < 0.05). In contrast, there was no significant difference in sodium or albumin transfer with Isc-Rep after Indo pretreatment (e.g., cerebral sodium Kin was 22.0 +/- 2.0 for Isc-Rep after Indo) compared with the control or Indo alone groups. Indo pretreatment effectively attenuates increased BBB transport of both sodium and albumin following cerebral ischemia. We conclude that products of PGH synthase are involved in BBB alterations of protein and cation transport that follow the early stages of cerebral reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
St. Jude Children's Research Hospital, Division of Critical Care and Pulmonary Medicine, Memphis 38101.
S L
SL
Zuckerman
R
R
Mirro
W M
WM
Armstead
M
M
Shibata
C W
CW
Leffler
D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D001810:Blood Volume; D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D015424:Reperfusion; D012711:Serum Albumin, Radio-Iodinated / Q000493:pharmacokinetics; D012964:Sodium / Q000493:pharmacokinetics; D013552:Swine
D012711:Serum Albumin, Radio-Iodinated; D012964:Sodium; D007213:Indomethacin