Fukuda Tatsuru, Nakashima Yoshifumi, Harada Miwa, Toyoshima Shigeki, Koshitani Osamu, Kawaguchi Yoshiro, Nakayama Mitsuo
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory Inc., Maya-cho, Naruto, Tokushima 772-8601, Japan.
J Toxicol Sci. 2006 Aug;31(3):229-34. doi: 10.2131/jts.31.229.
Although the toxic effects of citrate including hemodynamic and cardiovascular changes result from a decrease in ionized calcium levels in serum due to chelating action, these effects of citrate on blood coagulation have not yet been fully clarified. The present study examines whether serum citrate and ionized calcium levels affect whole blood clotting time in rats using the test tube method in which citrate is administered by rapid intravenous infusion. Citrate was infused via the tail vein into 10 rats at 3, 4 or 5 mmol/kg/hr for 1 hr, and then whole blood clotting time, serum citrate and ionized calcium levels were determined. Whole blood clotting time did not significantly change at citrate infusion rates of 3 and 4 mmol/kg/hr. However, at 5 mmol/kg/hr, whole blood clotting time was significantly prolonged by a factor of 2.1 relative to the untreated group, when the serum citrate level was 10.03 +/- 1.39 mmol/l (59.0-fold higher than that in the untreated group) and the serum-ionized calcium level was 0.29 +/- 0.02 mmol/l (0.2-fold lower than that in the untreated group). These results suggest that whole blood clotting time is significantly prolonged in rats with severe ionized hypocalcemia.
尽管柠檬酸盐的毒性作用（包括血流动力学和心血管变化）是由于螯合作用导致血清中离子钙水平降低所致，但柠檬酸盐对血液凝固的这些影响尚未完全阐明。本研究使用通过快速静脉输注给予柠檬酸盐的试管法，研究血清柠檬酸盐和离子钙水平是否会影响大鼠的全血凝固时间。将柠檬酸盐以3、4或5 mmol/kg/hr的速度通过尾静脉注入10只大鼠体内，持续1小时，然后测定全血凝固时间、血清柠檬酸盐和离子钙水平。在柠檬酸盐输注速率为3和4 mmol/kg/hr时，全血凝固时间没有显著变化。然而，在5 mmol/kg/hr时，当血清柠檬酸盐水平为10.03±1.39 mmol/l（比未处理组高59.0倍）且血清离子钙水平为0.29±0.02 mmol/l（比未处理组低0.2倍）时，全血凝固时间相对于未处理组显著延长了2.1倍。这些结果表明，严重离子性低钙血症的大鼠全血凝固时间会显著延长。
