The phosphodiesterase 3 inhibitor cilostazol dilates large cerebral arteries in humans without affecting regional cerebral blood flow

TY - JOUR

T1 - The phosphodiesterase 3 inhibitor cilostazol dilates large cerebral arteries in humans without affecting regional cerebral blood flow

AU - Birk, Steffen

AU - Kruuse, Christina Rostrup

AU - Petersen, Kenneth A

AU - Jonassen, Olga

AU - Tfelt-Hansen, Peer

AU - Olesen, Jes

PY - 2004/12

Y1 - 2004/12

N2 - 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.

AB - 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.

KW - 3',5'-Cyclic-AMP Phosphodiesterases

KW - Adult

KW - Blood Pressure

KW - Carbon Dioxide

KW - Cerebral Arteries

KW - Cerebrovascular Circulation

KW - Cyclic Nucleotide Phosphodiesterases, Type 3

KW - Double-Blind Method

KW - Female

KW - Heart Rate

KW - Humans

KW - Male

KW - Phosphodiesterase Inhibitors

KW - Tetrazoles

U2 - 10.1097/01.WCB.0000143536.22131.D7

DO - 10.1097/01.WCB.0000143536.22131.D7

M3 - Journal article

C2 - 15625409

SN - 0271-678X

VL - 24

SP - 1352

EP - 1358

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 12

ER -