Monitoring of the thromboxane A2/prostacyclin ratio in the urine of patients with retinal vascular occlusion through the low-dose-aspirin therapy using the gas chromatography/selected ion monitoring method.
We determined the levels of the stable urinary metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 2,3-dinor-6-keto-prostaglandin F1alpha (2,3-dinor-6-keto-PGF1alpha) in patients with retinal vascular occlusion (RVO) to elucidate the change of the thromboxane A2/prostacyclin (TX/PGI) ratio with this disease and the effect of low-dose-aspirin therapy. 11-Dehydro-TXB2 and 2,3-dinor-6-keto-PGF1alpha were converted to 1-methyl ester-propylamide-9,12,15-tris-dimethylisopropylsilyl ether derivative and 1-methyl ester-6-methoxime-9,12,15-tris-dimethylisopropylsilyl ether derivative, respectively, and applied to a gas chromatography/selected ion monitoring. The average level of 11-dehydro-TXB2 in 30 patients with RVO was 1038 +/- 958 pg/mg creatinine. It was significantly higher than that of 27 healthy volunteers, which was 616 +/- 294 pg/mg creatinine (p < 0.05 with unpaired t-test). However, 2,3-dinor-6-keto-PGF1alpha levels were not significantly different between these two groups. The average ratio of TX/PGI in the RVO patients was 32 +/- 26 and it was significantly higher than that of healthy volunteers, 17 +/- 10 (p < 0.01). Patients with central retinal artery occlusion or branch retinal artery occlusion showed greatly high 11-dehydro-TXB2 levels and TX/PGI ratios, although the number of patients was limited in the current study. After the administration of low-dose aspirin (40 mg/day) for about 1 month, the TX/PGI ratio decreased to around the normal level. Following the levels for up to 10 months, they also remained at the normal level. These observations suggested that the 11-dehydro-TXB2 levels and the TX/PGI ratio reflect the pathological conditions of RVO and are useful markers of the treatment.
Mizugaki
M
M
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan. mizugaki@mail.cc.tohoku.ac.jp
Hishinuma
T
T
Matsumura
E
E
Murai
Y
Y
Yamazaki
T
T
Yamanobe
S
S
Tamai
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011460:Prostaglandins F / Q000652:urine; D015356:Retinal Artery Occlusion / Q000175:diagnosis / Q000628:therapy*; D012170:Retinal Vein Occlusion; D013928:Thromboxane A2 / Q000652:urine*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013931:Thromboxanes / Q000652:urine
D011460:Prostaglandins F; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D011464:Epoprostenol; D001241:Aspirin