ACUTE EFFECTS OF INDOMETHACIN ON CEREBRAL BLOOD-FLOW IN MAN

Blood velocity changes in the internal carotid artery were estimated using Doppler ultrasound before, during and after injection of indometacin or placebo in 7 healthy adults. Upon injection of the active substance there was a rapid reduction in blood velocities in the internal carotid artery, increasing with increasing doses of indometacin. A fall in end-expiratory PCO2 was also observed, indicating a state of hyperventilation. The observed relative reduction in cerebral blood flow was much higher in all subjects than the expected reduction due to the accompanying drop in PCO2. Experiments in which arterial PCO2 was kept constant showed that indometacin also causes a reduction in blood velocity independent of changes in PCO2. We suggest that indometacin has both a direct effect on the cerebral microcirculation, and an additional effect mediated through induction of hyperventilation. The drug probably affects the respiratory center through an increase in intracerebral PCO2 due to reduced perfusion.