Evaluation of Oral Dimethyl Trisulfide (DMTS) as a Prophylactic Countermeasure for Oral Cyanide Toxicity in a Swine (Sus scrofa) Model

Cyanide (CN) is a deadly poison with various exposure routes. Currently, there are no FDA approved antidotes specific to oral CN. Dimethyl Trisulfide (DMTS) is a naturally occurring sulfur-based molecule used in food additives. Our objective was to evaluate the efficacy of DMTS when administered orally as prophylactic countermeasure against acute CN toxicity in swine. Twelve anesthetized Yorkshire swine (45-55 kg) were randomized to receive either prophylactic treatment with DMTS (n = 8,15 mg/kg), or DMTS diluent (untreated) controls (n = 4), delivered through the orogastric (OG) tube. Ten minutes post-DMTS or diluent administration, animals received oral potassium CN (KCN, 8 mg/kg). Animals were observed for 120 minutes after KCN administration, or until death criteria were met. Blood samples for arterial blood gases (ABGs), and hemodynamic parameters were collected. Data shown as mean ± SD; significance accepted at p < 0.05. All DMTS-treated animals had 100% survival through the observation period, while the control group had 0% survival (p < 0.0004). The average time of death and apnea for controls was 48 ± 23.7 and 9 ± 2.6 minutes respectively. Controls serum lactate levels were significantly higher 5 minutes post KCN (1.8±0.5) and continued to increase until death, vs. DMTS-treated (1.2±0.3), which remained comparable to baseline. Oral prophylactic DMTS treatment improved survival at 120 minutes in a large animal model of severe, acute oral cyanide toxicity. This study provides pre-clinical evidence of DMTS's efficacy as a countermeasure against oral cyanide toxicity as demonstrated by hemodynamics and blood gas analysis. Future experiments will evaluate DMTS's efficacy after KCN poisoning.