title: Effectiveness of isosorbide dinitrate in cyanide poisoning as a function of the administration timing.
abstract: Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders.
  
  
  
  A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 μg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH.
  
  
  
  Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved.
  
  
  
  Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning.
authors.affiliation: Clinical Pharmacology and Toxicology Unit, Carmel Medical Center, 7 Michal St., Haifa, 3436212, Israel. ophir.lavon@clalit.org.il.|Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. ophir.lavon@clalit.org.il.
authors.forename: Ophir
authors.initials: O
authors.lastname: Lavon
authors.affiliation: Pre Clinical Research Authority, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Avrahami
authors.affiliation: Institute for Research in Military Medicine, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Arik
authors.initials: A
authors.lastname: Eisenkraft
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D004334:Drug Administration Schedule; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D011041:Poisoning / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D011190:Potassium Cyanide / Q000097:blood / Q000506:poisoning*; D011817:Rabbits; D011897:Random Allocation; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; D011190:Potassium Cyanide
keywords: Animal; Antidote; Cyanide; Isosorbide dinitrate; Poisoning