Key result
Indapamide prolongs MAPD90 ~56% more in females than males during verapamil exposure.
Why the study?
Underlying mechanisms of drug-induced long QT syndrome and gender-related differences in cardiac repolarization are not fully understood in prepubertal subjects.
Are there gender-related differences in drug-induced prolongation of cardiac repolarization in prepubertal guinea pigs?
Population
120 prepubertal male and female guinea pigs
Comparison
IKs blocker (indapamide) vs IKr blockers (domperidone, dofetilide) with or without verapamil, male vs female
Design
Preclinical experimental study
Authors
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Hypothesis-generating for sex differences in prepubertal repolarization; clinical translation to children untested.
Are there gender-related differences in drug-induced prolongation of cardiac repolarization in prepubertal guinea pigs?
Absolute Event Rate: 15.1% vs 9.7%
p-value: p=< .05
Prepubertal female guinea pigs show greater susceptibility to I(Ks) block-induced repolarization prolongation compared to males, highlighting potential sex-specific mechanisms in drug-induced long QT syndrome.
Hreiche et al. (2009) studied Drug-induced long QT syndrome (n=120). Indapamide, domperidone, or dofetilide with or without verapamil vs. Males vs females was evaluated on Monophasic action potential duration at 90% repolarisation (MAPD90) prolongation (p=< .05). Indapamide prolonged the monophasic action potential duration at 90% repolarisation more in female than in male prepubertal guinea pigs treated with verapamil (15.1 vs 9.7 msec; P < .05).
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