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Methyl isocyanate inhalation induces tissue factor-dependent activation of coagulation in rats.
Rancourt, Raymond C; Rioux, Jacqueline S; Veress, Livia A; Garlick, Rhonda B; Croutch, Claire R; Peters, Eric; Sosna, William; White, Carl W.
Afiliación
  • Rancourt RC; a Department of Pharmacology and Toxicology Ernest Mario School of Pharmacy , Rutgers University , Piscataway , NJ , USA.
  • Rioux JS; b Department of Pediatrics , University of Colorado , Denver , CO , USA.
  • Veress LA; b Department of Pediatrics , University of Colorado , Denver , CO , USA.
  • Garlick RB; b Department of Pediatrics , University of Colorado , Denver , CO , USA.
  • Croutch CR; c MRIGlobal , Kansas City , MO , USA.
  • Peters E; c MRIGlobal , Kansas City , MO , USA.
  • Sosna W; c MRIGlobal , Kansas City , MO , USA.
  • White CW; b Department of Pediatrics , University of Colorado , Denver , CO , USA.
Drug Chem Toxicol ; 42(3): 321-327, 2019 May.
Article en En | MEDLINE | ID: mdl-30426789
Methyl isocyanate (MIC) is a highly toxic industrial chemical causing acute lethality after inhalation. The objective of this study was to determine whether alterations in hemostasis also occur in the immediate hours after exposure. Male rats were exposed to MIC (125-500 ppm) by nose-only vapor inhalation for 30 min. Arterial O2 saturation was monitored prior to exposure, and hourly thereafter. Rats were euthanized at 1, 2, 4, and 8 hr and plasma analyzed for recalcification clotting time, tissue factor (TF) activity, and protein levels. Hypoxemia, as assessed by pulse oximetry, was an early feature of MIC inhalation. In contrast to sham or low (125 ppm) concentrations, 250 and 500 ppm MIC caused significant declines in blood oxygen saturation (% SpO2) at 1 hr, which remained at deficit during the postexposure period. Commensurate with hypoxemia, plasma clotting time was significantly accelerated 1 hr after MIC inhalation (sham treatment: 955 ± 62.8 s; 125 ppm MIC: 790 ± 62 s; 250 ppm: 676 ± 28.0 s; 500 ppm: 581 ± 175 s). This procoagulant effect was transient, with no difference observed between sham and all MIC groups by 8 hr. Similarly, elevated TF activity and protein were detected in plasma 1 hr after MIC inhalation, each of which showed a progressive decline back to control levels at later timepoints. This study demonstrates that MIC inhalation resulted in hypoxemia and transient hypercoagulability of blood. Accelerated clotting occurred rapidly and was likely due to intravascular TF, which initiates the extrinsic coagulation pathway.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Coagulación Sanguínea / Tromboplastina / Isocianatos / Exposición por Inhalación Límite: Animals Idioma: En Revista: Drug Chem Toxicol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Coagulación Sanguínea / Tromboplastina / Isocianatos / Exposición por Inhalación Límite: Animals Idioma: En Revista: Drug Chem Toxicol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos