Alterations of atrial electrophysiology induced by electrolyte variations: combined computational and P-wave analysis

Abstract

Haemodialysis (HD) therapy represents a unique model to test in vivo, in humans, the effects of changes in plasma ionic concentrations. Episodes of paroxysmal atrial fibrillation (AF) often occur during the treatment. We investigated the effects of HD-induced electrolyte variations on atrial electrophysiology by analysing ECG P-wave duration (PWd), which reflects atrial conduction velocity (CV), and simulated atrial action potential (AP). In 20 end-stage renal disease patients PWd (signal-averaged ECG), heart rate (HR), blood pressure, Na(+), K(+), Ca(2+), and Mg(2+) plasma concentrations were measured before and after HD session. The Courtemanche computational model of human atrial myocyte was used to simulate the atrial AP. AP upstroke duration (AP(ud)), AP duration and atrial cell effective refractory period (ERP) were computed. Extracellular electrolyte concentrations and HR were imposed to the average values measured in vivo. HD decreased K(+) (from 4.9 +/- 0.5 to 3.9 +/- 0.4 mmol/L, P < 0.001) and Mg(2+) (0.92 +/- 0.08 to 0.86 +/- 0.05 mmol/L, P < 0.05), and increased Na(+) (139.8 +/- 3.4 to 141.6 +/- 3.1 mmol/L, P < 0.05) and Ca(2+) (1.18 +/- 0.09 to 1.30 +/- 0.07 mmol/L, P < 0.001) plasma concentrations. PWd systematically increased in all the patients after HD (131 +/- 11 to 140 +/- 12 ms, P < 0.001), indicating an intra-atrial conduction slowing. PWd increments were inversely correlated with K(+) variations (R = 0.73, P < 0.01). Model-based analysis indicated an AP(ud) increase (from 2.58 to 2.94 ms) after HD, coherent with experimental observations on PWd, and a reduction of ERP by 12 ms. Changes of plasma ionic concentrations may lead to modifications of atrial electrophysiology that can favour AF onset, namely a decrease of atrial CV and a decrease of atrial ERP.