The lack of transplacental movement of the cyanide antidote thiosulfate in gravid ewes.
A previous study reported that the co-infusion of IV sodium thiosulfate (STS) with sodium nitroprusside (SNP) to near-term gravid ewes prevented both maternal and fetal cyanide toxicity. We questioned whether maternally administered STS crossed the ovine placenta to enhance fetal transulfuration of cyanide, or whether the fetus was dependent on maternal detoxification of cyanide after diffusion of cyanide into the maternal circulation. Ten anesthetized, near-term gravid ewes underwent hysterotomies with delivery of fetal heads for venous catheterization. Five control ewes received IV isotonic sodium chloride solution, whereas five experimental ewes received IV STS (50 mg/kg over 15 min). Serial plasma thiosulfate concentrations in ewes and fetuses were measured over 135 min. Areas under the time-plasma thiosulfate concentration curves were calculated for experimental and control ewes at 2758+/-197 and 508+/-74 min x mg(-1) x L(-1), respectively (P < 0.008). Mean areas under the curve for experimental and control fetuses were 236+/-34 and 265+/-23 min x mg(-1) x L(-1), respectively (P > 0.5). Maternally administered STS may prevent fetal cyanide poisoning from SNP administration without relying on STS crossing the placenta into the fetal circulation. Fetal cyanide may cross down a concentration gradient from fetal to maternal circulation, to be transulfurated to thiocyanate in maternal tissues.


CONCLUSIONS
We evaluated the mechanism of action of sodium thiosulfide (STS) in sodium nitroprusside-induced cyanide toxicity in the ewe. Fetal cyanide poisoning is alleviated by maternal administration of STS, although this cyanide antidote apparently does not cross the placenta.
Graeme
K A
KA
Department of Medical Toxicology, Good Samaritan Regional Medical Center, Phoenix, Arizona, USA.
Curry
S C
SC
Bikin
D S
DS
Lo Vecchio
F A
FA
Brandon
T A
TA
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000633:toxicity; D003486:Cyanides / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005315:Fetal Diseases / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D008431:Maternal-Fetal Exchange; D009599:Nitroprusside / Q000493:pharmacokinetics / Q000633:toxicity; D011247:Pregnancy; D012756:Sheep; D013885:Thiosulfates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000931:Antidotes; D000959:Antihypertensive Agents; D003486:Cyanides; D013885:Thiosulfates; D009599:Nitroprusside; C017717:sodium thiosulfate