Effects of a selective inhibitor of cyclic AMP phosphodiesterase on the pial microcirculation in feline cerebral ischemia.

Abstract

We evaluated the effects of cilostazol, a selective inhibitor of cyclic adenosine monophosphate phosphodiesterase, on the pial vessels of adult cats subjected to endothelial damage followed by middle cerebral artery occlusion. Six cats were treated with cilostazol and four with 30% N,N-dimethylformamide in 70% saline (solvent). The brain surface was irradiated with ultraviolet rays through a cranial window for 3 minutes to selectively damage the endothelium of the pial vessels in both groups. Beginning 32 minutes after termination of the irradiation, the middle cerebral artery was occluded for 30 minutes. Thirty minutes before occlusion, intravenous infusion of 30 micrograms/kg/min cilostazol or 0.1 ml/kg/min solvent was begun and continued until the end of the study. Before occlusion, the infusion of cilostazol induced a significant (p less than 0.05) dilatation while the infusion of solvent produced no significant changes in the diameter of the pial arteries. The pial veins of solvent-treated cats showed significant (p less than 0.05) constriction during occlusion, whereas cilostazol-treated cats exhibited only mild constriction of the pial veins. The formation of platelet thrombi after occlusion was significantly (p less than 0.05) inhibited in the pial veins of cilostazol-treated compared with solvent-treated cats. Similarly, the microcirculation of the pial veins was effectively restored after reopening of the middle cerebral artery in cilostazol-treated compared with solvent-treated cats. Our data suggest that cilostazol is an effective antithrombotic agent as well as a potent vasodilator acting on vascular smooth muscle.