title: The phosphodiesterase 3 inhibitor cilostazol dilates large cerebral arteries in humans without affecting regional cerebral blood flow.
abstract: Cilostazol, an inhibitor of phosphodiesterase (PDE) type 3, is used clinically in peripheral artery disease. PDE3 inhibitors may be clinically useful in the treatment of delayed cerebral vasospasm after subarachnoid hemorrhage. The authors present the first results on the effect of cilostazol on cerebral hemodynamics in normal participants. In this double-blind, randomized, crossover study, 200 mg cilostazol or placebo was administered orally to 12 healthy participants. Cerebral blood flow was measured using 133Xe inhalation and single photon emission computerized tomography. Mean flow velocity in the middle cerebral arteries (VMCA) was measured with transcranial Doppler, and the superficial temporal and radial arteries diameters were measured with ultrasonography. During the 4-hour observation period, there was no effect on systolic blood pressure (P = 0.28), but diastolic blood pressure decreased slightly compared with placebo (P = 0.04). VMCA decreased 21.5 +/- 5.7% after cilostazol and 5.5 +/- 12.2% after placebo (P = 0.02, vs. placebo), without any change in global or regional cerebral blood flow. The superficial temporal artery diameter increased 17.6 +/- 12.3% (P < 0.001 vs. baseline) and radial artery diameter increased 12.6 +/- 8.6% (P < 0.001 vs. baseline). Adverse events, especially headache, were common. The findings suggest that cilostazol is an interesting candidate for future clinical trials of delayed cerebral vasospasm.
authors.affiliation: Danish Headache Center and Department of Neurology, University of Copenhagen, Glostrup University Hospital, Glostrup, Copenhagen, Denmark. birk@dadlnet.dk
authors.forename: Steffen
authors.initials: S
authors.lastname: Birk
authors.forename: Christina
authors.initials: C
authors.lastname: Kruuse
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Petersen
authors.forename: Olga
authors.initials: O
authors.lastname: Jonassen
authors.forename: Peer
authors.initials: P
authors.lastname: Tfelt-Hansen
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000077407:Cilostazol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D002245:Carbon Dioxide; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol