Effect of nordihydroguaiaretic acid on cerebral blood flow and metabolism during hypoxia in newborn piglets.

Abstract

Nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was investigated for its effect on cerebral blood flow (CBF) and cortical oxygen consumption during hypoxia in 9 anesthetized, ventilated newborn piglets. CBF was measured by radioactive microspheres while brain cortical metabolism was evaluated by continuous 31P-NMR spectroscopy. Five piglets were treated with NDGA (3 mg/kg i.v. in 50% ethanol as vehicle) prior to hypoxia and had CBF measured before NDGA (control), 15 min after NDGA (baseline) and then after 15 and 45 min of hypoxia following NDGA. Another 4 piglets were treated with vehicle (2 ml/kg 50% ethanol) under the same protocol. In the NDGA-treated piglets, cerebral cortical O2 consumption for a given PCr/Pi was significantly increased (p < 0.05) compared to non-NDGA. Since NDGA inhibits production of vasoconstricting leukotrienes during hypoxia, cortical capillary beds otherwise constricted may be perfused following NDGA, thus increasing the O2-consuming tissue area.