Document Detail


The lack of transplacental movement of the cyanide antidote thiosulfate in gravid ewes.
MedLine Citation:
PMID:  10589625     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. IMPLICATIONS: 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.
Authors:
K A Graeme; S C Curry; D S Bikin; F A Lo Vecchio; T A Brandon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  89     ISSN:  0003-2999     ISO Abbreviation:  Anesth. Analg.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  1999-12-30     Completed Date:  1999-12-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1448-52     Citation Subset:  AIM; IM    
Affiliation:
Department of Medical Toxicology, Good Samaritan Regional Medical Center, Phoenix, Arizona, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidotes / administration & dosage,  pharmacokinetics*
Antihypertensive Agents / pharmacokinetics,  toxicity
Cyanides / blood,  pharmacokinetics,  poisoning,  toxicity*
Disease Models, Animal
Female
Fetal Blood / metabolism
Fetal Diseases / blood,  metabolism,  prevention & control
Maternal-Fetal Exchange*
Nitroprusside / pharmacokinetics,  toxicity
Pregnancy
Sheep
Thiosulfates / administration & dosage,  blood,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/Antidotes; 0/Antihypertensive Agents; 0/Cyanides; 0/Thiosulfates; 15078-28-1/Nitroprusside; 7772-98-7/sodium thiosulfate

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