Right ventricular pacing with mechanical dyssynchrony causes apoptosis interruptus and calcium mishandling.
Can J Cardiol
; 29(4): 510-8, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23062666
ABSTRACT
BACKGROUND:
Mechanical dyssynchrony associated with rapid pacing induces cardiac cell stress and myocardial apoptotic pathway activation that has been implicated in the pathophysiology of left ventricular (LV) dysfunction. Effects of dyssynchrony per se are not fully understood. The objective of our study was to test whether ventricular dyssynchrony would elicit myocardial alterations in LV calcium handling regulation and cell survival or apoptosis signalling in right ventricular-paced swine.METHODS:
Implantation of pacemaker was performed under anaesthesia. Endocardial bipolar screw lead was inserted into the right jugular vein and positioned either in the right atrium or at the right ventricular (RV) apex. Swine were paced at 150 beats per minute for 3 weeks.RESULTS:
Compared with right atrial pacing, RV pacing led to abnormal LV sarcoplasmic reticulum calcium uptake (315 ± 65 vs 155 ± 55 nmol/min/mg, P < 0.05) and LV calcium-handling protein expression, ie, 35% reduction in ryanodine receptor 2, 25% decline in sarcoplasmic reticulum Ca(2+) ATPase, 70% increase in Na(+)/Ca(2+) exchanger, and 10% increase in phospholamban. RV pacing also elicited activation of LV apoptotic cascades without nuclear apoptosis. So-called interrupted apoptosis was the result of increased expression of X-linked inhibitor of apoptosis protein. Apoptosis and calcium mishandling were documented in absence of depressed heart function (ejection fraction 62 ± 8% vs 57 ± 12%, in right atrial- and RV-paced hearts, respectively, P > 0.05).CONCLUSIONS:
Slow rate RV pacing causes mechanical dyssynchrony and profound LV alterations in both apoptotic pathways and calcium handling in the early stages of pacing-induced cardiomyopathy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estimulação Cardíaca Artificial
/
Cálcio
/
Apoptose
/
Miócitos Cardíacos
/
Frequência Cardíaca
/
Ventrículos do Coração
/
Cardiomiopatias
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Can J Cardiol
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França