Effects of prostacyclin, indomethacin, and heparin on cerebral blood flow and platelet adhesion after multifocal ischemia of canine brain.

Abstract

Seven anesthetized dogs treated with prostaglandin I2, indomethacin, and heparin were compared with 12 controls to test the hypothesis that the salutary effect of treatment on recovery of neuronal function and cerebral blood flow (CBF) after ischemia is coupled to the inhibition of platelet accumulation. In this model of right hemisphere multifocal ischemia, cortical somatosensory evoked response (CSER) amplitude, 14C autoradiographic blood flow, and 111In-labeled platelet accumulation were measured. The ratio of injured to noninjured hemispheric 111In activity (cpm/g) provided an index of platelet accumulation. Treatment improved CBF of the injured hemisphere compared with control after 4 hours of reperfusion (74 +/- 17 versus 53 +/- 13 ml/100 g/min, p less than 0.05), and it enhanced recovery of CSER amplitude (percent of baseline) after 1 hour of reperfusion compared with control (27.1 +/- 4.7% [treatment] versus 15.5 +/- 2.8% [control], p less than 0.05). However, the effect on CSER was not sustained after 4 hours of recovery. Despite these effects on CSER and CBF, treatment failed to inhibit 111In-labeled platelet accumulation in the injured hemisphere (1.7 +/- 0.3% [treatment] versus 1.5 +/- 0.1% [control], p greater than 0.05). Platelets may adhere to damaged endothelium despite aggressive platelet antiaggregant therapy.