Cellular electrophysiological modulation in chronic atrial fibrillation - Studies with magnesium and GIK solution

Abstract: Although chronic atrial fibrillation (CAF) is the most common sustained cardiac arrhythmia in man, the mechanisms involved in its progressive course are still not fully understood. Recent studies have verified an electrical remodelling of the atrial myocardium that may be responsible for the electrophysiological disturbances known to exist in the fibrillating atria. The electrical remodelling is linked to a defect intracellular calcium handling that seems to involve an increased release of the ion from the sarcoplasmic reticulum. Furthermore, the arrhythmia is associated with a depolarised resting membrane potential of the atrial muscle verified by several authors. Both these mechanisms may at least in part be modulated by magnesium and GIK solution interfering with the intracellular calcium overload and depolarised resting membrane potential, respectively. By investigating the potential effects of magnesium alone and in combination with GIK solution in an animal model and during chronically perpetuated atrial fibrillation in man, several significant effects were obtained. Magnesium prolonged the action potential duration at 90 % repolarisation in guinea pig atrial muscle and increased the atrial refractoriness during CAF. Resting membrane potential was slightly depolarised with higher concentrations of magnesium consistent with an increased intraatrial conduction delay after DC-conversion of CAF. The AV-nodal function during CAF is characterised by dual conduction pathways responsible for the ventricular response. The two AV-nodal conduction pathways were differently affected by magnesium and GIK solution. The autonomic nervous system decreased the atrial refractoriness during CAF, which is in accordance with the proarrhythmic effect of enhanced activity of either limb. These investigations suggest that magnesium in combination with GIK solution may have beneficial electrophysiological effects during CAF.