title: Effect of whole blood clotting time in rats with ionized hypocalcemia induced by rapid intravenous citrate infusion.
abstract: 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.
authors.affiliation: Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory Inc., Maya-cho, Naruto, Tokushima 772-8601, Japan. fukudat2@otsukakj.co.jp
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Fukuda
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Miwa
authors.initials: M
authors.lastname: Harada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Toyoshima
authors.forename: Osamu
authors.initials: O
authors.lastname: Koshitani
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D019343:Citric Acid / Q000097:blood / Q000633:toxicity*; D006996:Hypocalcemia / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014914:Whole Blood Coagulation Time
chemical_list: D019343:Citric Acid; D002118:Calcium