Combination pharmacotherapy in the treatment of experimental cardiac arrest

Am J Emerg Med. 2009 Jul;27(6):651-9. doi: 10.1016/j.ajem.2008.05.004.

Abstract

Study objectives: Full recovery after cardiopulmonary resuscitation (CPR) is poor. We hypothesized that the coadministration of epinephrine, a beta-blocker such as atenolol, and a calcium sensitizer such as levosimendan during CPR would improve survival and postresuscitation myocardial function.

Methods: Ventricular fibrillation was induced in 60 piglets, which were left untreated for 8 minutes before attempted resuscitation. Animals were randomized into 4 groups (n = 15), to receive epinephrine (group E), epinephrine + atenolol (group E + A), epinephrine + levosimendan (group E + L) and epinephrine + atenolol + levosimendan (group E + A + L) during CPR. Electrical defibrillation was attempted 2 minutes after drug administration.

Results: Five animals in group E survived for 48 hours in comparison to 8 animals in groups E + A and E + L and 12 animals in group E + A + L. Postresuscitation cardiac output was significantly better in the animals of group E + A + L. Troponin I remained significantly lower in groups E + A and E + A + L. Serum astroglial protein (S-100) and neuron-specific enolase values in group E + L and E + A + L were statistically lower than those measured in groups E and E + A during the entire observation period. The neurologic alertness score was higher in group E + A + L compared to groups E and E + A.

Conclusions: The administration of a drug combination of epinephrine + atenolol + levosimendan, when given during CPR, in a pig model of cardiac arrest, results in improved 48-hour survival and improves postresuscitation cardiac function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / therapeutic use*
  • Animals
  • Atenolol / therapeutic use*
  • Cardiotonic Agents / therapeutic use*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Epinephrine / therapeutic use*
  • Heart Arrest / drug therapy*
  • Hydrazones / therapeutic use*
  • Lactic Acid / blood
  • Phosphopyruvate Hydratase / blood
  • Pyridazines / therapeutic use*
  • S100 Proteins / blood
  • Simendan
  • Swine
  • Troponin I / blood

Substances

  • Adrenergic beta-Agonists
  • Cardiotonic Agents
  • Hydrazones
  • Pyridazines
  • S100 Proteins
  • Troponin I
  • Lactic Acid
  • Simendan
  • Atenolol
  • Phosphopyruvate Hydratase
  • Epinephrine