Combination pharmacotherapy in the treatment of experimental cardiac arrest

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.

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.

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.

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.