Although cardiorespiratory complications contribute to the high morbidity/mortality of
familial dysautonomia (FD), the mechanisms remain unclear. We evaluated respiratory, cardiovascular, and cerebrovascular control by monitoring ventilation, end-tidal
carbon dioxide (CO2-et), oxygen saturation, RR interval, blood pressure (BP), and midcerebral artery flow velocity (MCFV) during progressive isocapnic
hypoxia, progressive hyperoxic
hypercapnia, and during recovery from moderate
hyperventilation (to simulate changes leading to respiratory arrest) in 22 subjects with FD and 23 matched control subjects. Subjects with FD had normal ventilation, higher CO2-et, lower oxygen saturation, lower RR interval, and higher BP. MCFV was also higher but depended on the higher baseline CO2-et. In the FD group, whereas hyperoxic
hypercapnia induced normal cardiovascular and ventilatory responses, progressive
hypoxia resulted in blunted increases in ventilation, paradoxical decreases in RR interval and BP, and lack of MCFV increase.
Hyperventilation induced a longer
hypocapnia-induced apneic period (51.5 +/- 9.9 versus 11.2 +/- 5.5 seconds, p < 0.008) with profound desaturation (to 75.8 +/- 3.5%), marked BP decrease, and RR interval increase. Subjects with FD develop central depression in response to even moderate
hypoxia with lack of expected change in cerebral circulation, leading to
hypotension,
bradycardia,
hypoventilation, and potentially respiratory arrest. Higher resting BP delays occurrence of
syncope during
hypoxia. Therapeutic measures preventing
hypoxia/
hypocapnia may correct cardiovascular accidents in patients with FD.