Summary:
The end of 80ies and the beginning of 90ies in arrhythmology was characterized by the demonstration
of so called proarrhythmia, when drugs, particularly antiarrhythmic ones, induced serious,
frequently fatal arrhythmias. The resulting pharmacotherapeutic skepsis in the treatment of,
in particular, ventricular arrhythmias were accompanied at the same time by a powerful development
of non-pharmacological modes of treatment of arrhythmias, especially by implantable defibrillators.
The causes of proarrhythmia were identified with the evolution of knowledge in the
genetic basis of hereditary syndrome of long QT interval. The first mutation was identified in 1991
and other mutations in the four subsequent years. The mutated genes controlling the synthesis of
ionic membrane channels cause disorders in the repolarization phase of action potential. Their
expression in individual types of myocytes is not homogenous, most affected being the M cells of
ventricular myocardium. It results in a dispersion of repolarization which, together with induction
of early after depolarization, causes the origin of polymorphic ventricular tachycardia – TdP.
In the 90ies of 20th century there were increasingly frequent reports on sudden arrhythmic death
in patients, who had been treated with non-cardiac drugs. They were caused by polymorphic
ventricular tachycardia associated with the long QT interval. The syndrome was named as acquired
syndrome of long QT interval, based on the drug-induced delayed repolarization of myocyte.
The slowing-down is caused by affected membrane channels known from the syndrome of hereditary
LQTS. The very low frequency of these fatal complications has been explained either by an
obscure genetic defect or a disorder in metabolism of the therapeutic drug, but especially due to
drug interactions metabolized in a similar way and similarly influencing the function of membrane
channels. Sixty drug molecules with proarrhythmic potential have been identified so far, but
the list is probably not complete yet.
Key words:
Anti-arrhythmic drugs - Pro-arrhythmia - Non-pharmacological modes of arrhythmia
treatment - Syndrome of long-term QT interval - Polymorphic ventricular tachycardias - Phase of
action potential re-polarization
|