INDOMETHACIN REDUCES ISCHEMIA-INDUCED ALTERATION OF BLOOD-BRAIN-BARRIER TRANSPORT IN PIGLETS

Cerebral ischemia-reperfusion (Isc-Rep) alters blood-brain barrier (BB B) transport properties in piglets. Pretreatment with superoxide dismu tase and catalase partially attenuates these effects. Activated O-2 sp ecies produced with Isc-Rep in piglets are generated via prostaglandin (PG) H synthase. This experiment determines if products of PGH syntha se alter BBB transport of sodium and albumin. Piglets anesthetized wit h nitrous oxide and halothane were divided into four groups: 1) contro l, 2) indomethacin (5 mg/kg iv) with no Isc-Rep, 3) Isc-Rep alone, and 4) Isc-Rep after pretreatment with indomethacin (Indo). Regional tran sfer coefficients (K-in) and regional cerebral blood flow (microsphere s) were measured at 2 h reperfusion after 20 min total global cerebral ischemia. K-in values are represented as absolute values and also rel ative to blood flow to account for any changes in perfusion caused by ischemia and/or Indo. Indo alone did not alter sodium or albumin trans fer compared with control animals. Isc-Rep alone caused a significant increase in sodium and albumin transport compared with all other group s (control cerebral sodium K-in was 18.2 +/- 2.7 cm(3) g(-1) s(-1) 106 vs. 32.9 +/- 3.1 for Isc-Rep, P < 0.05). In contrast, there was no si gnificant difference in sodium or albumin transfer with Isc-Rep after Indo pretreatment (e.g., cerebral sodium K-in 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 so dium and albumin following cerebral ischemia. We conclude that product s of PGH synthase are involved in BBB alterations of protein and catio n transport that follow the early stages of cerebral reperfusion. Such findings suggest that products of arachidonic acid metabolism by PGH synthase contribute to Isc-Rep endothelial dysfunction.