Changes in cerebrovascular prostaglandins and thromboxane as a function of systemic blood pressure. Cerebral blood flow autoregulation of the newborn

Abstract

Cerebrovascular concentrations of prostaglandin E (PGE), prostaglandin F(2α) (PGF(2α)), 6-ketoprostaglandin F(1α) (6-keto-PGF(1α)), and thromboxane B2 (TXB2) were determined over a blood pressure range of 17-117 mm Hg (induced by inflation of balloon-tipped catheters placed in the thoracic descending aorta and at the aortic root) in eight newborn piglets to assess the role of prostanoids in cerebral blood flow (CBF; measured using radioactive microspheres) autoregulation. Basal systemic blood pressure, heart rate, blood gases, total CBF, and prostanoid concentrations were stable. CBF was constant between 50 and 90 mm Hg, but beyond this range CBF varied directly with blood pressure (τ = 0.48; p < 0.05). Sagittal sinus concentrations of PGE, PGE(2α), and 6-keto-PGF(1α) varied with blood pressure according to a quadratic function (R2 = 0.92 to 0.96, p < 0.0001), exhibiting lowest values between mean blood pressures of 60 and 90 mm Hg. During hypotension (17-49 mm Hg), there was a greater relative increase in sagittal sinus concentrations of TXB2 than of PGE, PGF(2α), and 6-keto-PGF(1α); at the lowest blood pressures, TBX2 increased by 658 ± 44%, and prostaglandins increased on the average by 331 ± 49% (p < 0.01) from their values during normotension (50-90 mm Hg). During hypertension (91-117 mm Hg), cerebrovascular production and concentrations of prostaglandins increased by 142 ± 31% and 45 ± 10%, respectively, but did not change for TXB2. Based on these findings we speculate that the marked increase in the potent vasoconstrictor thromboxane during hypotension may set the lower limit of CBF autoregulation to a blood pressure of 50 mm Hg and that the increase in vasodilator prostaglandins during hypertension may contribute to the pressure passivity of CBF above 90 mm Hg. These data may imply that the increase in cerebrovascular prostaglandins during relatively mild elevations in blood pressure may lead to distention and ultimately rupture of cerebral blood vessels in the newborn.