Mitochondrial ATP Synthase Tetramer Disassembly following Blood-Based or del Nido Cardioplegia during Neonatal Cardiac Surgery.
J Extra Corpor Technol
; 54(3): 203-211, 2022 Sep.
Article
em En
| MEDLINE
| ID: mdl-36742212
ABSTRACT
Conservation of mitochondrial adenosine triphosphate (ATP) synthase proteins during ischemia is critical to preserve ATP supply and ventricular function. Following myocardial ischemia in adults, higher order ATP synthase tetramer proteins disassemble into simpler monomer units, reducing the efficiency of ATP production. However, it is unknown if myocardial ischemia following the use of cardioplegia results in tetramer disassembly in neonates, and whether it can be mitigated by cardioplegia if it does occur. We investigated myocardial ATP synthase tetramer disassembly in both a neonatal lamb cardiac surgery model and in neonatal children requiring cardiac surgery for the repair of congenital heart disease. Neonatal lambs (Ovis aries) were placed on cardiopulmonary bypass (CPB) and underwent cardioplegic arrest using a single dose of 30 mL/kg antegrade blood-based potassium cardioplegia (n = 4) or a single dose of 30 mL/kg antegrade del Nido cardioplegia (n = 6). Right ventricular biopsies were taken at baseline on CPB (n = 10) and after approximately 60 minutes of cardioplegic arrest before the cross clamp was released (n = 10). Human right ventricular biopsies (n = 3) were taken following 40.0 ± 23.1 minutes of ischemia after a single dose of antegrade blood-based cardioplegia. Protein complexes were separated on clear native gels and the tetramer to monomer ratio quantified. From the neonatal lamb model regardless of the cardioplegia strategy, the tetramermonomer ratio decreased significantly during ischemia from baseline measurements (.6 ± .2 vs. .5 ± .1; p = .03). The del Nido solution better preserved the tetramermonomer ratio when compared to the blood-based cardioplegia (Blood .4 ± .1 vs. del Nido .5 ± .1; p = .05). The tetramermonomer ratio following the use of blood-based cardioplegia in humans aligned with the lamb data (tetramermonomer .5 ± .2). These initial results suggest that despite cardioprotection, ischemia during neonatal cardiac surgery results in tetramer disassembly which may be limited when using the del Nido solution.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
/
Isquemia Miocárdica
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Procedimentos Cirúrgicos Cardíacos
Tipo de estudo:
Observational_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article