Told Reinhard, Fuchsjäger-Mayrl Gabriele, Wolzt Michael, Popa-Cherecheanu Alina, Schmetterer Leopold, Garhofer Gerhard
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
Microvasc Res. 2014 Mar;92:85-90. doi: 10.1016/j.mvr.2014.01.004. Epub 2014 Jan 18.
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.
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.
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).
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.
己酮可可碱是一种非选择性磷酸二酯酶抑制剂,在某些血管床显示出血管舒张作用并降低血液粘度。我们之前已经表明,在血管收缩状态下,循环红细胞与白细胞之间的相互作用可能在血流控制中发挥作用。这一观察结果的原因尚不完全清楚,但可能与红细胞和白细胞之间的机械相互作用有关。在本研究中,我们假设己酮可可碱可能会在氧诱导的血管收缩过程中改变这种相互作用。
24名健康男性受试者参与了这项双盲、随机、安慰剂对照的双向交叉试验。为了增加白细胞计数(WBC),静脉注射300μg粒细胞集落刺激因子(G-CSF)。通过吸氧诱导视网膜血管收缩。在两个不同的研究日输注400mg己酮可可碱或安慰剂。用蓝域内视技术评估白细胞通量。用动态血管分析仪(DVA)测量血管口径,用激光多普勒测速仪(LDV)测定红细胞速度(RBCV)。根据视网膜血管直径和RBCV计算视网膜血流量。
在安慰剂组和己酮可可碱组中,G-CSF的给药均导致白细胞显著增加(两组均p<0.01)。己酮可可碱的给药未改变视网膜血管直径、RBCV、计算出的视网膜血流量和白细胞流量。高氧导致视网膜血流参数显著降低。在吸氧期间,两组在血管直径(p=0.54)、RBCV(p=0.34)、计算出的视网膜血流量(p=0.3)和白细胞流量(p=0.26)方面未观察到差异。
我们的数据表明,在白细胞增多期间,短期给予己酮可可碱不会改变氧对眼部血流参数的影响。长期治疗是否能在血管收缩状态下改善视网膜血流仍有待研究。