Simvastatin Shows Antiarrhythmic Effects

During the investigation adult mongrel canines were anticoagulated with heparin (180 IU/kg) and anaesthetised with sodium pentobarbital (35 mg/kg, intravenously). Transmembrane action potentials were recorded from the superfused left superior or inferior pulmonary vein (PV) sleeves using standard microelectrode techniques.

Acetylcholine (1 μM), isoproterenol (1 μM), high calcium ([Ca2+]o = 5.4 mM), or a combination was used to induce early afterdepolarisations (EADs) or delayed afterdepolarisations (DADs) and triggered activity. Voltage clamp experiments were performed in the left atrium measuring fast and late sodium currents.

Researchers found that, under steady-state conditions, simvastatin (10 nM, n = 9) induced a small increase in action potential duration measured at 85% repolarisation and a significant decrease in action potential amplitude, take-off potential, and maximum rate of rise of action potential upstroke at the fastest rates.

The Vmax decreased from 175.1 ± 34 V/s to 151.7 ± 28 V/s and from 142 ± 47 V/s to 97.4 ± 39 V/s at basic cycle lengths of 300 and 200 ms, respectively. Simvastatin (10 to 20 nM) eliminated DADs and DAD-induced triggered activity in 7 of 7 PV sleeve preparations and eliminated or reduced late-phase 3 EADs in 6 of 6 PV sleeve preparations. Simvastatin (20 nM) did not affect late or fast sodium currents measured using voltage clamp techniques.

The authors observe that other agents with upstream effects and direct actions to reduce electrical remodeling during rapid activation of the atria, such as the antihypertensive agents losartan and enalapril, have been shown in preliminary reports to have similar effects. They call for further clinical studies to evaluate the role of statins in the prevention and treatment of atrial arrhythmias.