Comparative Efficacy of three Methemoglobin Formers in Delaying Effects of Infused Sodium Cyanide

Abstract

A prophylactic treatment is needed to circumvent constraints of the current therapy for cyanide (CN-) intoxication: intravenous administration of sodium nitrite and sodium thiosulfate. Experiments were conducted to compare the anticyanide effects of three candidate pretreatment methemoglobin (MHb)-forming compounds in an anesthetized animal model. The experiment was conducted in 5 periods, with each of 9 animals receiving the vehicle control in period 1, 0.2 mg/kg p-aminopropiophenone (PA PP) in period 2, and 2.5 mg/kg WR242511 in period 3. Four of the animals received the vehicle control in period 4 followed by 7 mg/kg p-aminoheptanophenone (PA HP) in period 5, and 5 animals received 7 mg/kg PA HP in period 4 followed by the vehicle control in period 5. Sodium cyanide (Na CN) infusions for PAPP, PAHP, and WR242511 experiments were initiated when the predicted MHb level was approximately 5%. Infusions were stopped 10 s after no functional breaths (respiratory arrest) were observed. Blood samples were collected for hemoglobin (Hb), MHb, and total blood CN levels at scheduled time points. Time to respiratory arrest, percent MHb, and Na CN dose were the primary response parameters. A 11 pretreatment regimens effectively mitigated the effects of Na CN poisoning compared to the vehicle control (p <.05). No discernable differences in protection were provided by the three compounds. The results indicated that the protective effect is related to the MHb level rather than the specific pretreatment drug.