Interaction between leukocytes and erythrocytes in the human retina: effects of pentoxifylline on hyperoxia-induced vasoconstriction during increased neutrophil counts.
OBJECTIVE
Pentoxifylline, a nonselective phosphodiesterase inhibitor, shows vasodilator effects in certain vascular beds and reduces blood viscosity. We have previously shown that under states of vasoconstriction an interaction between circulating erythrocytes and leukocytes may play a role in the control of blood flow. The reason for this observation is not entirely clear but may be related to a mechanical interaction between red and white blood cells. In the present study we hypothesized that pentoxifylline may alter this interaction during oxygen-induced vasoconstriction.


METHODS
24 healthy male subjects participated in this double masked, randomized, placebo-controlled 2 way cross over trial. In order to increase white blood cell count (WBC) count, 300 μg of G-CSF was administered intravenously. Vasoconstriction of retinal vessels was induced by oxygen inhalation. 400mg of pentoxifylline or placebo was infused at two different study days. White blood cell flux was assessed with the blue-field entoptic technique. Vessel calibers were measured with a dynamic vessel analyzer (DVA) and red blood cell velocity (RBCV) was determined with laser Doppler velocimetry (LDV). Retinal blood flow was calculated based on retinal vessel diameters and RBCV.


RESULTS
Administration of G-CSF induced a significant increase in WBC, both in the placebo and the pentoxifylline group (p<0.01 for both groups). Retinal vessel diameter, RBCV, calculated retinal blood flow and white blood cell flow were not altered by administration of pentoxifylline. Hyperoxia induced a pronounced decrease in retinal blood flow parameters. No difference was observed between groups during oxygen breathing in vessel diameters (p=0.54), RBCV (p=0.34), calculated retinal blood flow (p=0.3) and white blood cell flow (p=0.26).


CONCLUSIONS
Our data indicate that short time administration of pentoxifylline does not alter the oxygen-induced effect on ocular blood flow parameters during leukocytosis. Whether long-term treatment could improve retinal blood flow under states of vasoconstriction remains to be investigated.
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
Reinhard
R
Told
Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
Gabriele
G
Fuchsjäger-Mayrl
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Michael
M
Wolzt
Department of Ophthalmology, Emergency University Hospital, Bucharest, Romania.
Alina
A
Popa-Cherecheanu
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
Leopold
L
Schmetterer
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. Electronic address: gerhard.garhoefer@meduniwien.ac.at.
Gerhard
G
Garhofer
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004912:Erythrocytes / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D000078224:Lenograstim; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology; D007964:Leukocytosis / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012171:Retinal Vessels / Q000187:drug effects* / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult
D010726:Phosphodiesterase Inhibitors; D011994:Recombinant Proteins; D014665:Vasodilator Agents; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D010431:Pentoxifylline