ZP123 reduces energy required for defibrillation by preventing connexin43 remodeling during prolonged ventricular fibrillation in swine.
Tex Heart Inst J
; 39(6): 784-91, 2012.
Article
em En
| MEDLINE
| ID: mdl-23304014
ABSTRACT
In ventricular fibrillation, the uncoupling of gap junctions slows conduction velocity and increases action-potential dispersion, which slows and diminishes defibrillation. We studied how the peptide ZP123, a gap-junction enhancer, might lower defibrillation-energy requirements during ventricular fibrillation in live pigs. We randomly assigned 33 pigs into 3 groups ZP123 (receiving a 1-µg/kg bolus and 10 µg/kg/hr of ZP123), control (receiving saline solution), and sham (undergoing a sham operation). After a 30-min administration of agents, ventricular fibrillation was induced and left untreated for 8 min. Biphasic defibrillation of 50 J was increased by 50-J increments as necessary. Defibrillation-energy requirements were defined as the lowest energy required to achieve defibrillation. Electrocardiographic values were obtained before and after the administration of agents. Western blot and immunofluorescence analyses were performed on ventricular myocardial samples. All but one pig survived. The ZP123 treatment did not alter electrocardiographic variables. In the ZP123 group, the average required defibrillation energy was lower than that in the control group (327.28±269.6 vs 610±192.64 J; P=0.015), and the cumulative percentage of successful defibrillation at upper energy levels was higher (P<0.05). Supraventricular rhythm occurred more often in the ZP123 group than in the control group (72.7% vs 50%, P=0.042). Western-blot and immunofluorescence results showed that ZP123 did not alter the total amount of connexin43 but did prevent its dephosphorylation. We conclude that ZP123 can reduce defibrillation-energy requirements by preventing connexin43 remodeling during prolonged ventricular fibrillation.
Palavras-chave
Anti-arrhythmia agents/administration & dosage/therapeutic use; arrhythmias, cardiac/prevention & control; connexin 43/analysis/metabolism; gap junctions/drug effects/metabolism/physiology; models, cardiovascular; phosphorylation/drug effects; swine; treatment outcome; ventricular fibrillation/therapy
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Fibrilação Ventricular
/
Cardioversão Elétrica
/
Conexina 43
/
Remodelação Ventricular
/
Eletrocardiografia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article