Abstract 223: A Case for Hypoxia and Long QT Syndrome in Sudden Infant Death Syndrome

Abstract

INTRODUCTION: Long QT syndrome is considered an important factor in the pathogenesis of Sudden Infant Death Syndrome (SIDS). Prolonged QTc intervals (c=corrected for heart rate) in SIDS are sometimes caused by mutations in genes encoding ion channels. Other causes remain largely idiopathic. HYPOTHESIS: Risk factors for SIDS, including maternal bed sharing, head covering and high altitude, are associated with a reduced oxygen environment. Our studies investigate a link between hypoxia and long QT syndrome in the neonate. METHODS: We characterised, for the first time, changes in the murine neonatal electrocardiogram (ECG) at: 0, 1, 3, 6, 12, 24 hours (n=12) and 2, 6 and 10 days (n=25) after birth. We investigated whether birth into hypoxia 10% O2 (n=16) and genetically elevating cardiac hypoxic signalling in neonatal mice alters the course of changes in ECG morphology (n=14). We analysed the ECG for heart rate and parameters associated with dysrrhythmia and sudden death, including the QTc interval. RESULTS: In the hours and days following birth, we observed a steady increase in heart rate (p<0.0001) and decrease in QTc interval (p<0.05). When neonates were raised in hypoxia for 24 hours, the trends in heart rate (p<0.001) and QTc interval (p<0.0001) were abolished and risk of neonatal death was 52% (17 out of 33) over 24 hours. In transgenic neonatal mice with elevated cardiac hypoxic signalling, we observed a significant bradycardia (p<0.0001) and elongated QTc interval (p<0.0001) compared to controls at ten days after birth, with death occurring pre-weaning. >CONCLUSIONS: Following birth there are significant changes in ECG morphology, including an increase in heart rate and decrease in QTc interval. Hypoxia diminishes these changes resulting in bradycardia and elongated QTc intervals. We hypothesise that the increase in ambient oxygen concentration after birth drives the maturation of cardiac electrical conduction, failure of which predisposes to dysrhythmia and sudden death. This is consistent with known risk factors of SIDS and provides a link between neonatal hypoxia and ECG repolarisation abnormalities.