Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern.
Cardiovasc Res
; 117(4): 1078-1090, 2021 03 21.
Article
em En
| MEDLINE
| ID: mdl-32402067
ABSTRACT
AIMS:
Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism. METHODS ANDRESULTS:
Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum. Enhanced GJ coupling with rotigaptide (n = 10) progressively organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM 0.53 ± 0.04, 80 nM 0.78 ± 0.03, P < 0.001), increasing RA-sustained VF time (0 nM 44 ± 6%, 80 nM 94 ± 2%, P < 0.001), and stabilized RAs (maximum rotations for an RA; 0 nM 5.4 ± 0.5, 80 nM 48.2 ± 12.3, P < 0.001). GJ uncoupling with carbenoxolone progressively disorganized VF; the FDI decreased (0 µM 0.60 ± 0.05, 50 µM 0.17 ± 0.03, P < 0.001) and RA-sustained VF time decreased (0 µM 61 ± 9%, 50 µM 3 ± 2%, P < 0.001). In CF, VF activity was disorganized and the RA-sustained VF time was the lowest (CF 27 ± 7% vs. PF 75 ± 5%, P < 0.001). Global fibrillatory organization measured by FDI was highest in PF (PF 0.67 ± 0.05 vs. CF 0.33 ± 0.03, P < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy 1411 ± 266 ms vs. compact 354 ± 38 ms, P < 0.001). DiF (n = 11) exhibited an intermediately organized VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs.CONCLUSION:
The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organization in VF, ranging between globally organized fibrillation sustained by stable RAs and disorganized, possibly multiple-wavelet driven fibrillation with no RAs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Ventricular
/
Potenciais de Ação
/
Junções Comunicantes
/
Ventrículos do Coração
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido