Effects of purified endogenous inhibitor of the Na+/Ca2+ exchanger on ouabain-induced arrhythmias in the atria and ventricle strips of guinea pig

Previous studies demonstrated that the purified endogenous inhibitor (NCXIF) of the cardiac Na+/Ca2+ exchanger (NCX1) has the capacity to modulate cardiac muscle contractility. Here, we tested the effects of purified NCXIF on arrhythmias induced by ouabain in the atria and ventricle strips of guinea pig. For the sake of comparison NCXIF was compared to lidocaine and KB-R7943. In the ventricle strip, NCXIF (∼ 10 U/ml) results in rapid, complete and stable inhibition of ouabain-induced arrhythmias (the inhibition of arrhythmia is not followed by revival of irregular contractions). Under similar experimental conditions the atria strips require somewhat higher doses of NCXIF (25–50 U/ml) for complete suppression of arrhythmia. In the atria strip, NCXIF (10–25 U/ml) increases the threshold dose (1 μM) of ouabain for arrhythmia onset 2.2 ± 0.5-fold (n = 5, p < 0.05) as well as prolongs the lag-phase for arrhythmia appearance 4.0 ± 0.5-fold (n = 5, p < 0.01). The lag period for arrhythmia onset was also lengthened (2.0 ± 0.4-fold) by NCXIF in the ventricle strips (n = 6, p < 0.002). At low frequency of pacing (1 Hz), all three tested substances, lidocaine, KB-R7943, and NCXIF can effectively suppress the ouabain-induced arrhythmia. However, at higher frequency (2 Hz), lidocaine is ineffective in suppressing arrhythmia, whereas KB-R7943 becomes pro-arrhythmic. In contrast to reference drugs, NCXIF retains its anti-arrhythmic capacity at high frequencies, either in the atria (n = 6, p < 0.01) or ventricle (n = 5, p < 0.05) strips. In conclusion, NCXIF results in rapid, effective and stable suppression of arrhythmia both in the atria and ventricle preparations under conditions at which the reference drugs become ineffective.