Details

Autor(en) / Beteiligte

• DE GROOT, Joris R
• SCHUMACHER, Cees A
• VERKERK, Arie O
• BAARTSCHEER, Antonius
• FIOLET, Jan W. T
• CORONER, Ruben

Titel

Intrinsic heterogeneity in repolarization is increased in isolated failing rabbit cardiomyocytes during simulated ischemia

Ist Teil von

• Cardiovascular research, 2003-09, Vol.59 (3), p.705-714

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2003

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Myocardial ischemia and ventricular arrhythmias often complicate congestive heart failure. Ischemia-induced dispersion in repolarization is an important arrhythmogenic factor that might be caused by intrinsic cellular differences in response to simulated ischemia (SI) or by changed coupling of myocytes. We hypothesized that intrinsic heterogeneity in action potential duration (APD) or the occurrence of rigor is larger in failing than in normal rabbit myocytes during SI. Heart failure (HF) was induced with volume and pressure overload. Left ventricular myocytes from apex, free wall and base were enzymatically isolated and exposed to SI with NaCN. There were no baseline differences in APD before SI. During SI no differences in time to inexcitability occurred but the range in APD increased more in HF than in normal cells. Rigor occurred after 16.8+/-3.5 and 23.0+/-7.5 min (P<0.05) in normal and HF myocytes, with no differences between apical, free wall or base cells. Variance in time to rigor was larger in HF than in normal cells (55.7 versus 12.4 min(2)). Blockade of anaerobic reserve decreased variance in time to rigor, also when normalized to mean, in HF and normal myocytes. In coupled normal and HF cell pairs, no delay in action potential propagation or differences in APD occurred during SI, and time to rigor was synchronized (P<0.05 vs. single cells). Intercellular differences in APD and in time of rigor arise in normal and HF myocytes subjected to SI, and are inhibited by blockade of anaerobic glycolysis. Dispersion in APD and tolerance to SI is increased in HF cells. APD and time to rigor are completely synchronized in coupled cell pairs.