Cardioprotective effect of glucose-insulin on acute propafenone toxicity in rat

Am J Emerg Med. 2012 Jun;30(5):680-9. doi: 10.1016/j.ajem.2011.03.011.

Abstract

Objective: We recently observed a case of propafenone self-poisoning in which the patient was initially unresponsive to conventional therapies such as sodium bicarbonate, dopamine, and norepinephrine but recovered with intravenous glucose-insulin infusion. We raised the hypothesis that insulin may have a cardioprotective effect in acute propafenone toxicity.

Methods: We evaluated the effect of glucose-insulin infusion on mortality and electrocardiographic abnormalities during acute propafenone toxicity in rats. After measurements of basal mean arterial pressure, heart rate, PR interval, and QRS duration, rats received intravenous propafenone (36 mg/kg per hour) for 12 minutes. Two minutes after the induction of toxicity, the rats (n=10 per group) received either normal saline solution (NSS) or insulin with glucose. Rats in the insulin-treated (Insulin group) and the NSS-treated (NSS group) groups received an intravenous infusion of 36 mg/kg per hour of propafenone until death occurred. Rats receiving only NSS intravenously without propafenone toxicity served as control (Control group, n=10).

Results: Insulin treatment improved survival and delayed the hemodynamic and electrocardiographic consequences of propafenone toxicity. Survival was significantly greater in the insulin group than that in the NSS group (P<.001). Insulin prevented the decline in mean arterial pressure and heart rate (P<.05). Insulin also prevented the increase of the PR interval and the QRS duration (P<.05).

Conclusion: Glucose-insulin infusion delayed the abnormalities in cardiac conduction and improved rat survival after acute propafenone toxicity. These results suggest a cardioprotective effect of glucose-insulin in acute propafenone toxicity.

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / antagonists & inhibitors
  • Anti-Arrhythmia Agents / toxicity*
  • Blood Pressure / drug effects
  • Cardiotonic Agents / therapeutic use*
  • Drug Therapy, Combination
  • Electrocardiography
  • Glucose / administration & dosage
  • Glucose / therapeutic use*
  • Heart Rate / drug effects
  • Infusions, Intravenous
  • Insulin / administration & dosage
  • Insulin / therapeutic use*
  • Male
  • Propafenone / antagonists & inhibitors
  • Propafenone / toxicity*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Arrhythmia Agents
  • Cardiotonic Agents
  • Insulin
  • Propafenone
  • Glucose