Respiratory and cerebrovascular responses to hypoxia and hypercapnia in familial dysautonomia.

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.