Effect and mechanism of esmolol given during cardiopulmonary resuscitation in a porcine ventricular fibrillation model

Abstract

Objectives The aim of the study was to investigate the effect on calcium cycling protein and electrical restitution of β 1-adrenergic receptor antagonist esmolol administered during cardiopulmonary resuscitation in the porcine ventricular fibrillation model. Methods Ventricular fibrillation untreated for four minutes was induced by dynamic steady state pacing protocol in 40 healthy male pigs, in which local unipolar electrograms were recorded using one 10-electrode catheter that was sutured to the left ventricular epicardium. During CPR, animals were randomized into two groups to receive saline as placebo or esmolol after two standard doses of epinephrine. At post-resuscitation 2-h, six pigs were randomly selected from each group and the second VF induction was performed. Local activation-recovery intervals (ARI) restitutions and the VF inducibility between control group and esmolol group were compared. Western blotting was performed to determine expression of Ca 2+/calmodulin-dependent protein kinase IIδ(CaMKIIδ) and cardiac ryanodine receptor (RyR2) protein, and their phosphorylation status. Results Injection of esmolol combined with epinephrine during CPR significantly decreased recurrent rate of ventricular fibrillation during 2-h post-resuscitation, meanwhile it has no adverse affect on the restore of spontaneous circulation. Esmolol significantly flattened ARI restitution slope, lessened regional difference of ARI restitution, decreased the VF inducibility, and alleviated CaMKIIδ hyper-activation and RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR has significant effects on modulating electrical restitution property and intracellular calcium handling, which contributes the most important reasons why β 1-blockade significantly reduced the onset and maintenance of VF.