Effect of hypercapnia and hypoxia on sympathetic and parasympathetic tone in Ondine syndrome

Abstract

Introduction Congenital central hypoventilation syndrome (CCHS, or Ondine's curse syndrome), a rare genetic disease, is characterized by a deficient respiratory response to hypoxia and hypercapnia, associated to vagal dysfunction. Serendipitous observations of restored ventilatory response to hypercapnia associated to progestin led to the hypothesis that oral contraceptive treatment (desogestrel or levonorgestrel) might also improve vagal activity. This was assessed by analyses of heart rate variability (HRV) during hypercapnic and hypoxic challenges. Methods ECG was recorded in 5 CCHS adult women enrolled in the RESPIRONDINE study ( NCT01243697 ): – during normoxia; – during hypercapnia (CO 2 rebreathing); – during progressive hypoxia. High frequency versus high plus low frequency (HF n.u., reflects parasympathetic control) and high frequency versus low frequency power (LF/HF, reflects sympathetic activity) were calculated, without (before or after a washout of 4 months) or during oral contraceptive treatment. Results During normoxia, LF/HF (2.43 ± 0.17 ms 2 ), HF n.u. (0.31 ± 0.03) and HR (82.6 ± 2.18 bpm) remained statistically unaffected by the progestative treatment ( P = 0.85, P = 0.83 and P = 0.93, respectively). During hypercapnic challenges and independently of contraceptive treatment ( n = 5), we observed a decrease in LF/HF ( P = 0.004 and P P P = 0.005). During hypoxic challenges and independently of the progestative treatment ( n = 3), an increase in LF/HF was always observed. Conclusions CCHS patients display an increase in the parasympathetic tone and a decrease in the sympathetic tone during hypercapnia. They also display an increase in sympathetic tone during hypoxia. This is similar to what occurs in healthy subjects. These results suggest a relative preservation of chemoreception that influences the cardiac function but probably not ventilation.