Effect of indomethacin on the regulation of cerebral blood flow during respiratory alkalosis in newborn piglets.
The effect of cyclooxygenase inhibition by indomethacin on regional cerebral blood flow (CBF) during hypocapnia induced by hyperventilation and during hypercapnia induced by CO2 inhalation was examined. CBF was measured in 27 anesthetized, ventilated piglets (2-8 d) using microspheres in control and indomethacin treated animals (5 mg/kg) after hyperventilation or inhalation of 6% CO2. In the control group (n = 6), CBF decreased significantly (p less than 0.05) to all regions of the brain after hyperventilation with a 32% decrease in the cerebral cortex. In the indomethacin-treated group (n = 6), blood flow significantly decreased by 35 to 49% in all regions of the brain, except the cerebral white matter, during normocapnia with no further decrease in flow during subsequent hypocapnia. Although CBF increased significantly after indomethacin treatment during hypercapnia the response was markedly attenuated with blood flow to the cerebral gray matter, hippocampus and pons rising only 42, 25, and 42% in contrast to 108, 75, and 225% in the control group. Since indomethacin decreased resting CBF, unilateral sympathetic nerve stimulation at 15 Hz was used to test the specificity of indomethacin on hypocapnic vasoconstriction (n = 5). Unilateral sympathetic nerve stimulation caused a further statistically significant decrease in CBF on the stimulated side after hyperventilation with indomethacin (12%), which was comparable to that which occurred during normocapnia (16%). The data demonstrate that indomethacin attenuates the cerebrovascular sensitivity to both increases and decreases in CO2/H+ and implicate a possible role for vasoactive prostanoids in mediating the response of CBF to fluctuations in CO2 in newborn piglets.
DeGiulio
P A
PA
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Roth
R A
RA
Mishra
O P
OP
Delivoria-Papadopoulos
M
M
Wagerle
L C
LC
D000472:Alkalosis, Respiratory / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004558:Electric Stimulation; D006935:Hypercapnia / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology*; D013552:Swine; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects
D002245:Carbon Dioxide; D007213:Indomethacin