The Role of Intralipid Emulsion in the Rat Model of Digoxin Intoxication

Cardiovasc Toxicol. 2018 Aug;18(4):329-336. doi: 10.1007/s12012-018-9444-4.

Abstract

Although the mechanism of action is not well known, intravenous lipid emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that, ILE probably separates the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high-dose free fatty acids activating the voltage-gated calcium channels in the myocytes. In this study, effects of ILE treatment on digoxin overdose were searched in an animal model in terms of cardiac side effects and survival. Forty Sprague-Dawley rats were divided into five groups. As the pre-treatment, the groups were administered saline, ILE, DigiFab and DigiFab and ILE. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest observation times were recorded. According to the results, there was no statistically significant difference among the group in terms of first arrhythmia time and cardiac arrest times. However, when the saline group compared with ILE-treated group separately, significant difference was observed. DigiFab, ILE or ILE-DigiFab treatment make no significant difference in terms of the first arrhythmia and cardiac arrest duration in digoxin-intoxicated rats. However, it is not possible to say that at the given doses, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the subgroup analysis, the study should be repeated with larger groups.

Keywords: Digital intoxication; Digoxin intoxication; Intralipid; Intralipid emulsion; Rat model.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidotes / pharmacology*
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control*
  • Cardiotoxicity
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Cytoprotection
  • Digoxin*
  • Disease Models, Animal
  • Fat Emulsions, Intravenous / pharmacology*
  • Fatty Liver / pathology
  • Fatty Liver / prevention & control
  • Heart Arrest / chemically induced
  • Heart Arrest / physiopathology
  • Heart Arrest / prevention & control*
  • Immunoglobulin Fab Fragments / pharmacology*
  • Kidney / drug effects
  • Kidney / pathology
  • Liver / drug effects
  • Liver / pathology
  • Rats, Sprague-Dawley

Substances

  • Antidotes
  • Fat Emulsions, Intravenous
  • Immunoglobulin Fab Fragments
  • digoxin antibodies Fab fragments
  • Digoxin