The effects of alterations of plasma electrolytes on post-repolarisation refractoriness
C Corrado, C H Roney, S M Narayan, W R Giles, S A NiedererAbstract
Background
Post-repolarisation refractoriness (PRR) measures the time during which cardiac tissue remains unexcitable despite the membrane potential having returned to its resting level. PRR plays a key role in determining tissue excitability, conduction safety, and its propensity to initiate and/or sustain atrial arrhythmias. Alterations in plasma potassium ([K+]o), sodium ([Na+]o), and calcium ([Ca²+]o) concentrations are common in clinical settings and can modulate atrial electrophysiology. These changes may differentially affect normal and fibrotic tissue, thereby modifying conduction, repolarisation, and refractoriness.
Purpose
To quantify how physiologically relevant variations in plasma electrolyte concentrations influence atrial conduction velocity (CV), action potential duration (APD), and post-repolarisation refractoriness (PRR) in both normal and fibrotic atrial tissue.
Methods
Computer simulations of atrial cell and tissue electrophysiology were used to assess the effects of mild alterations in [K+]o (4.5 mM ± 33%), [Na+]o (140 mM ± 25%), and [Ca²+]o (1.8 mM ± 25%) on CV, APD, and PRR. Global sensitivity analysis quantified the relative contribution of each electrolyte variation.
Results
Alterations in [Na+]o affected APD (Panel A, left) through the Na+/Ca²+ exchanger (INaCa, Panel B, left); alterations in [K+]o affected CV (Panel A, right) through the inward rectifier current (IK1, Panel B, right). Plasma alterations had small effects on PRR in healthy tissue (Panel C). On fibrotic tissue, however, PRR changed significantly and in a quasi-linear fashion, in response to alterations of either [K+]o or [Na+]o The same changes were exacerbated at a cycle length of 400 ms, with PRR becoming negative during hypokalaemia and/or failing to initiate an action potential during hyperkalaemia or hypernatremia. Alterations in [Ca²+]o had no significant effects on the biomarkers.
Conclusions
Mild alterations in [K+]o or [Na+]o significantly influence post-repolarisation refractoriness and hence arrhythmia vulnerability, whereas variations in [Ca²+]o have minimal effects. Low values of [K+]o or [Na+]o enhance the pro-arrhythmic substrate and may reduce the likelihood of successful cardioversion.