What is the clinical evidence from this study?

Study design: Other. Population: Post-acidosis ventricular arrhythmia. Intervention: Computer simulation of pH restoration protocols vs. Normal conditions. Primary outcome: Generation of delayed afterdepolarizations (DADs) and premature ventricular complexes (PVCs).

March 30, 2017Open Access

Mechanisms Underlying the Emergence of Post-acidosis Arrhythmia at the Tissue Level: A Theoretical Study

JBJieyun BaiFirst Affiliated Hospital of Jinan University RYRenli YinSouth China Agricultural University KWKuanquan WangElectrophysiology

Key Result

Computer simulations demonstrated that acidosis-induced sarcoplasmic reticulum calcium overload and altered source-sink interactions increase susceptibility to post-acidosis ventricular arrhythmias.

Structured PICO

Does simulated acidosis and subsequent pH recovery induce delayed afterdepolarizations and re-entry arrhythmias in human ventricular tissue models?

Population

Computer models of human ventricular cells (modified ten Tusscher-Panfilov TP06 model) incorporated into 1D fiber (100 myocytes) and 2D sheet (100 × 500 grid points) tissue models

Intervention

Simulated acidosis (intracellular pH 6.7) followed by post-acidosis (pH 7.15) with varying pH recovery rates (0.1 to 4 minutes)

Comparator

Normal physiological pH conditions (pH 7.15)

Outcome

Emergence of delayed afterdepolarizations (DADs), premature ventricular complexes (PVCs), and vulnerability to unidirectional conduction block leading to re-entrysurrogate

Computational modeling demonstrates that acidosis-induced cellular electrophysiological alterations and altered source-sink interactions increase susceptibility to post-acidosis ventricular arrhythmias.

Limitations

The study relies on theoretical computer models which may not fully capture the complex in vivo environment of human ischaemia-reperfusion injury.

Abstract

Acidosis has complex electrophysiological effects, which are associated with a high recurrence of ventricular arrhythmias. Through multi-scale cardiac computer modeling, this study investigated the mechanisms underlying the emergence of post-acidosis arrhythmia at the tissue level. In simulations, ten Tusscher-Panfilov ventricular model was modified to incorporate various data on acidosis-induced alterations of cellular electrophysiology and intercellular electrical coupling. The single cell models were incorporated into multicellular one-dimensional (1D) fiber and 2D sheet tissue models. Electrophysiological effects were quantified as changes of action potential profile, sink-source interactions of fiber tissue, and the vulnerability of tissue to the genesis of unidirectional conduction that led to initiation of re-entry. It was shown that acidosis-induced sarcoplasmic reticulum (SR) calcium load contributed to delayed afterdepolarizations (DADs) in single cells. These DADs may be synchronized to overcome the source-sink mismatch arising from intercellular electrotonic coupling, and produce a premature ventricular complex (PVC) at the tissue level. The PVC conduction can be unidirectionally blocked in the transmural ventricular wall with altered electrical heterogeneity, resulting in the genesis of re-entry. In conclusion, altered source-sink interactions and electrical heterogeneity due to acidosis-induced cellular electrophysiological alterations may increase susceptibility to post-acidosis ventricular arrhythmias.

Ask AI

Helpful

Bookmark

View Full Paper