Transmural action potential repolarization heterogeneity develops postnatally in the rabbit.
BACKGROUND
In the hereditary long QT syndrome, arrhythmia risk changes with age despite the presence of an ion channel mutation throughout development. Age-dependent changes in the transmural dispersion of repolarization may modulate this vulnerability. We recorded cardiac action potentials in infant, periadolescent, and adult rabbit myocardium to determine if transmural heterogeneities in repolarization are developmentally determined.


RESULTS
Arterially perfused ventricular preparations were studied from 2-week (n = 7), 7-week (n = 7), and adult (n = 6) NZW rabbits. Action potentials were recorded with microelectrodes in five regions: epicardium (epi), subepicardium (subepi), midwall (mid), subendocardium (subendo), and endocardium (endo) during endocardial S1 pacing at cycle lengths of 2,000, 1,000, and 500 ms. At 2 weeks, the transmural APD90 profile was flat. With age, APD prolongation from subepi to endo created a transmural repolarization gradient. At 7 weeks, APD90 was significantly longer at subendo [204 +/- 2 ms (mean +/- SE) 2,000-ms cycle length, P < 0.05] vs both endo (193 +/- 2 ms) and epi (172 +/- 2 ms), causing a heterogeneous transmural APD90 gradient. In adults, the transmural gradient was a smooth continuum such that APD was shortest in epicardium and longest in endocardium.


CONCLUSIONS
The transmural distribution of APD is developmentally determined. Tissue-specific age-dependent changes in APD can result in transmural repolarization heterogeneity. These age-related effects may modulate arrhythmia vulnerability during development.
Idriss
Salim F
SF
Pediatric Cardiology, Department of Pediatrics, Duke University, Durham, North Carolina 27710, USA. salim.idriss@duke.edu
Wolf
Patrick D
PD
D000200:Action Potentials / Q000502:physiology*; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D004562:Electrocardiography; D011817:Rabbits; D016277:Ventricular Function, Left / Q000502:physiology*