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

Full Abstract

OBJECTIVES: 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.

Author information

Author/s: Jingjun, Lü (L); Yan, Zhang (Z); Weijie, (); Dongdong, Zhao (Z); Guosheng, Lin (L); Mingwei, Bao (B);

Affiliation: Department of Emergency Medicine, RenMin Hospital of Wuhan University, Wuhan 430060, China. lvjingjun(-atsign-)gmail.com

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Resuscitation (Resuscitation), published in Ireland. (Language: eng)

Reference: 2009-Sep; vol 80 (issue 9) : pp 1052-9

Dates: Created 2009/08/17; Completed 2009/11/05;

PMID: 19581034, status: MEDLINE (last retrieved date: 11/5/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Male
Phosphorylation - drug effects
Phosphotransferases
Propanolamines - administration & dosage; therapeutic use
Ryanodine Receptor Calcium Release Channel - biosynthesis; drug effects
Treatment Outcome
Ventricular Fibrillation - metabolism; physiopathology; therapy
Ventricular Function - drug effects; physiology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Adrenergic beta-Antagonists (0) ; Propanolamines (0) ; Ryanodine Receptor Calcium Release Channel (0) ; esmolol (84057-94-3) ; Phosphotransferases (EC 2.7.-) ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17)

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