Obstructive sleep apnea (OSA) is now recognized as a major risk factor for cardiovascular disorders including ventricular arrhythmias and sudden cardiac death. We have demonstrated that intermittent hypoxia (IH), a major component of OSA, increases the incidence of myocardial ischemiarelated ventricular fibrillation. The aim of the present study was to investigate the mechanisms behind the arrhythmogenic effects of IH.

Wistar rats were exposed to IH (60-sec cycles alternating 21 and 5% FiO2, 8h/day) or normoxia (similar air-air cycles) during 14 days. Arterial blood pressure and ECG were recorded for power spectral analysis and ECG interval measurement. Hearts were removed, perfused in Langendorff mode and paced at 300 bpm. Epicardial and endocardial monophasic action potentials were recorded and action potential duration at 50% repolarization (APD50) was measured.

Mean arterial blood pressure was significantly increased by IH exposure. Rats exposed to IH exhibited higher low-frequency (LF) power, lower high-frequency (HF) power and higher LF/HF ratio of heart rate and blood pressure variability, indicative of a systemic sympathetic activation. This was corroborated by a significant increase in circulating norepinephine levels. IH exposure also resulted in a significant increase in QTc and Tpeak- Tend intervals, indicative of increased spatial and transmural dispersion of repolarization and associated with an increased vulnerability to ischemic ventricular arrhythmias. The increase in the transmural repolarization gradient was associated with a significantly longer endocardial APD50 in IH-exposed rats (49.07±2.19ms) compared to normoxia-exposed rats (41.29±0.62ms, p<0.01) while epicardial APD50 did not differ.

Thus, chronic exposure to intermittent hypoxia, such as that occurring during OSA, promotes a pro-arrhythmogenic state characterized by sympathoactivation and alterations in ventricular repolarization.

The author hereby declares no conflict of interest