Effect and mechanism of esmolol given during cardiopulmonary resuscitation in a porcine ventricular fibrillation model.
OBJECTIVE
The aim of the study was to investigate the effect on calcium cycling protein and electrical restitution of beta(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 IIdelta(CaMKIIdelta) 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 CaMKIIdelta 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 beta(1)-blockade significantly reduced the onset and maintenance of VF.
Jingjun
Lü
L
Department of Emergency Medicine, RenMin Hospital of Wuhan University, Wuhan 430060, China. lvjingjun@gmail.com
Yan
Zhang
Z
Weijie
Dongdong
Zhao
Z
Guosheng
Lin
L
Mingwei
Bao
B
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis / Q000187:drug effects; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D019837:Ryanodine Receptor Calcium Release Channel; D010770:Phosphotransferases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C036604:esmolol