title: The effects of intravenous lipid emulsion on prolongation of survival in a rat model of calcium channel blocker toxicity.
abstract: BACKGROUND
  Intravenous lipid emulsion (ILE) has been shown to ameliorate the toxicity of lipid-soluble agents in animal studies and clinical cases.
  
  
  OBJECTIVE
  To investigate the therapeutic effects of ILE in a rat model of toxicity from calcium channel blockers (CCBs), including diltiazem and nicardipine.
  
  
  METHODS
  Two sets of experiments of CCB poisoning were conducted. In the first set, 14 male Sprague-Dawley rats were sedated and treated with ILE or normal saline (NS), followed by continuous intravenous infusion of diltiazem (20 mg/kg/h). In the second experiment, the study protocol was the same except the infusion of nicardipine (20 mg/kg/h). The total dose of infused drug and the duration of survival were measured. In addition, mean arterial pressure and heart rate were monitored.
  
  
  RESULTS
  Survival was prolonged in the ILE group (48.4 ± 11.3 vs. 25.0 ± 3.7 min; p = 0.002). Furthermore, the cumulative mean lethal dose of diltiazem was higher in the ILE group (16.1 ± 3.8 mg/kg) than in the NS group (8.3 ± 1.1 mg/kg) (p = 0.002). With nicardipine poisoning, survival was also prolonged in the ILE group (71.0 ± 8.3 min vs. 30.6 ± 6.1 min; p = 0.002). The cumulative mean lethal dose was higher in the ILE group than in the NS group (23.7 ± 2.8 mg/kg vs. 10.2 ± 2.0 mg/kg; p = 0.002).
  
  
  CONCLUSIONS
  ILE pretreatment prolonged survival and increased the lethal dose in a rat model of CCB poisoning using diltiazem and nicardipine.
authors.affiliation: Department of Emergency Medicine, Gyeongsang National University School of Medicine , Jinju , Korea.
authors.forename: Changwoo
authors.initials: C
authors.lastname: Kang
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Seong Chun
authors.initials: SC
authors.lastname: Kim
authors.forename: Soo Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Jeong
authors.forename: Tae-Sin
authors.initials: TS
authors.lastname: Kang
authors.forename: Il-Woo
authors.initials: IW
authors.lastname: Shin
authors.forename: Rock Bum
authors.initials: RB
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004110:Diltiazem; D004195:Disease Models, Animal; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009529:Nicardipine; D011041:Poisoning / Q000188:drug therapy* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000931:Antidotes; D002121:Calcium Channel Blockers; D005217:Fat Emulsions, Intravenous; D009529:Nicardipine; D004110:Diltiazem
keywords: Antidote; Cardiotoxins; Drug overdose; Poisoning