Background: Nifekalant, a class III anti-arrhythmic agent, has been used clinically at serum concentrations of 1-10 μmol/L in patients with ventricular arrhythmias. However, the effect of nifekalant on triggered arrhythmias has not yet been established. Methods and Results: Trabeculae were dissected from the right ventricles of 16 rat hearts. The force was measured using a silicon strain gauge, the membrane potential using ultra-compliant microelectrodes, and the regional intracellular Ca2+ ([Ca 2+]i) using electrophoretically microinjected fura-2 and an image intensified CCD camera at a sarcomere length of 2.1 μm. Rapid cooling contractures (RCCs) were measured to estimate the Ca2+ content in the sarcoplasmic reticulum. Ca2+ waves and aftercontractions were measured after the induction of reproducible Ca 2+ waves. Nifekalant at 1, 10 and 250 μmol/L increased significantly the action potential duration, the peak [Ca2+] i, the developed force and the amplitude of RCCs in a concentration-dependent manner (stimulus interval=2 s, [Ca2+] o=0.7 mmol/L, 26.0±0.2°C). Nifekalant at 10 and 250 μmol/L increased significantly the velocity of Ca2+ waves with an enhancement of the aftercontractions (stimulus interval=0.5 s for 7.5 s, [Ca2+]o= 1.8±0.1 mmol/L, 22.3±0.5°C). Conclusions: Nifekalant, even at a therapeutic concentration, can increase muscle contraction, but may worsen triggered arrhythmias because of the acceleration of Ca2+ waves under Ca2+-overloaded conditions.
- Ca wave
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine