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

ABSTRACT: Cilostazol is a drug used for the treatment of intermittent claudication caused by narrowing of the blood vessels and reduced oxygen supply, characterized by intense pain in the leg when walking. This study was designed to investigate the effect of cilostazol on the P50 of the oxygen hemoglobin dissociation curve. A total of eight healthy adult subjects were studied. Blood samples (0.5 mL) from each subject were mixed with 5, 10, and 20 μL of the 0.5 mg/mL stock solution of cilostazol to give concentrations of 10, 20, and 40 µg/mL equivalent to adult doses of 50, 100, and 200 mg, respectively. The control sample had no drug added. The oxygen hemoglobin dissociation curve of each sample was plotted and the P50 determined with a Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA). The mean P50 for the control samples was 28.27 ± 0.43 mm Hg. The values of the samples exposed to 10, 20, and 40 µg/mL cilostozol were 29.63 ± 0.66, 30.15 ± 0.77, and 31.66 ± 0.62 mm Hg, respectively. There was a statistically significant difference (p < 0.01) between the control and samples exposed to 40 µg/mL cilostazol. This study suggests that cilostazol caused an increase in the release of oxygen from hemoglobin as shown in the P50 values. This effect was significant at the highest concentration of 40 µg/mL.

SUBMITTER: McKoy M

PROVIDER: S-EPMC4347826 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Project description:Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P < .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003). Reproduction of the MR imaging-based oxygen-hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion MR imaging-based oxygen-hemoglobin dissociation curves and oxygen-hemoglobin affinity information were derived for pregnant mice by using 9.4-T MR imaging, which suggests a potential to overcome the need for direct sampling of fetal or maternal blood. Online supplemental material is available for this article.

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

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