Effect of cilostazol on the p50 of the oxygen-hemoglobin dissociation curve.

Cilostazol (Pletoz, Cipla Ltd., Mumbai, India) is a drug used to treat intermittent claudication, a condition caused by narrowing of the arteries supplying the legs with blood. The narrowing of the blood vessels and consequent reduction in oxygen availability is usually accompanied by pain. The pain associated with intermittent claudication worsens during walking and improves at rest. Intermittent claudication is reportedly the most common symptom of arterial insufficiency in peripheral artery disease.1 Cilostazol is a selective inhibitor of the phosphodiesterase (PDE) III isoenzyme. PDE III is involved in the degradation of cyclic adenosine monophosphate (cAMP). Inhibition of the action of PDE III suppresses the breakdown of cAMP and thus increases the amount of cAMP in tissues.2 3 This dilates blood vessels and increases the flow of blood and, as a result, oxygen to the legs. In addition, the cAMP reduces platelet aggregation. Cilostazol is therefore of therapeutic benefit in intermittent claudication. Long-term use of the drug reportedly increases walking distances in patients with peripheral artery disease.1 Cilostazol is typically administered orally as 100 mg tablets twice daily and its absorption increases with a high fat meal.4 Cilostazol has been reported to normalize the level of erythrocyte 2,3 diphosphoglycerate in sucrose-fed Otsuka Long-Evans Tokushima (OLTEFT) fatty rats which had a reduction in 2,3 diphosphoglycerate.5 The metabolite 2,3 diphosphoglycerate in the erythrocyte shifts the oxygen hemoglobin dissociation curve to the right resulting in increased oxygen release.6 The oxygen hemoglobin dissociation curve is important clinically as it provides information on the relationship between partial pressure of oxygen and the oxygen saturation of arterial blood, which may have implications especially in circulatory diseases. The P50 is the partial oxygen pressure at which hemoglobin is 50% saturated with oxygen; the average value reported with the Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA) is 25.3 ± 1.5 mm Hg.7 Based on the ability of cilostazol to normalize the level of erythrocyte 2,3 diphosphoglycerate, it was hypothesized that cilostazol would shift the oxygen hemoglobin dissociation curve to the right and increase oxygen release from erythrocytes. This study was therefore designed to investigate the effect of cilostazol on the P50 of the oxygen hemoglobin dissociation curve of normal blood.