Effects of the non-selective phosphodiesterase inhibitor pentoxifylline on regional cerebral blood flow and large arteries in healthy subjects.
The vasodilating properties of the non-selective phosphodiesterase (PDE) inhibitor pentoxifylline were evaluated. Pentoxifylline has been reported to increase cerebral blood flow (CBF) and improve recovery rate of stroke patients. Whether these results are due to a dilating effect on arteries or to other mechanisms is not clear. In the present double-blind crossover study, 10 healthy subjects received pentoxifylline 300 mg or placebo intravenously on separate days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by transcranial Doppler and rCBF was measured using (133)Xenon-inhalation SPECT. High-frequency ultrasound was used for measurements of temporal and radial artery diameter. Cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) concentrations were assessed in plasma. Except for increased heart rate (P < 0.05), systolic blood pressure (P < 0.05) and plasma cAMP (P < 0.001), no significant differences in CBF, rCBF(mca) or plasma cGMP were seen between placebo and pentoxifylline infusion. During pentoxifylline infusion, V(mca) decreased 7.2% (SD 12.0; P < 0.05) and temporal artery diameter increased 9.0% (SD 7.0; P < 0.001), suggesting minor dilatation of the large arteries. However, this change was not significantly different from placebo. In conclusion, pentoxifylline 300 mg had no effect on rCBF. A possible minor dilatation of the middle cerebral artery and the temporal artery cannot be excluded. Any potential clinical effect of pentoxifylline is most likely mediated through non-vascular mechanisms.
Kruuse
C
C
Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600 Glostrup Copenhagen, Denmark. ckruuse@dadlnet.dk
Jacobsen
T B
TB
Thomsen
L L
LL
Hasselbalch
S G
SG
Frandsen
E K
EK
Dige-Petersen
H
H
Olesen
J
J
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010865:Pilot Projects; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D017585:Ultrasonography, Doppler, Transcranial
D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline