Previous studies demonstrated that the purified endogenous inhibitor (NCX(IF)) of the cardiac
Na(+)/Ca(2+) exchanger (NCX1) has the capacity to modulate cardiac muscle contractility. Here, we tested the effects of purified NCX(IF) on arrhythmias induced by
ouabain in the atria and ventricle strips of guinea pig. For the sake of comparison NCX(IF) was compared to
lidocaine and
KB-R7943. In the ventricle strip, NCX(IF) ( approximately 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 NCX(IF) (25-50 U/ml) for complete suppression of
arrhythmia. In the atria strip, NCX(IF) (10-25 U/ml) increases the threshold dose (1 microM) 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 NCX(IF) in the ventricle strips (n=6, p<0.002). At low frequency of pacing (1 Hz), all three tested substances,
lidocaine,
KB-R7943, and NCX(IF) 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, NCX(IF) 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, NCX(IF) 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.