Combination pharmacotherapy in the treatment of experimental cardiac arrest.
OBJECTIVE
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.
Xanthos
Theodoros
T
Department of Experimental Surgery and Surgical Research, University of Athens, Medical School, 11527 Athens, Greece. theodorosxanthos@yahoo.com
Bassiakou
Eleni
E
Koudouna
Eleni
E
Rokas
Georgios
G
Goulas
Sotirios
S
Dontas
Ismene
I
Kouskouni
Evaggelia
E
Perrea
Despina
D
Papadimitriou
Lila
L
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000627:therapeutic use*; D006323:Heart Arrest / Q000188:drug therapy*; D006835:Hydrazones / Q000627:therapeutic use*; D019344:Lactic Acid / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011724:Pyridazines / Q000627:therapeutic use*; D009418:S100 Proteins / Q000097:blood; D000077464:Simendan; D013552:Swine; D019210:Troponin I / Q000097:blood
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D009418:S100 Proteins; D019210:Troponin I; D019344:Lactic Acid; D000077464:Simendan; D001262:Atenolol; D010751:Phosphopyruvate Hydratase; D004837:Epinephrine