Cardio-respiratory Uncoupling in Congenital Central Hypoventilation Syndrome

Congenital central hypoventilation syndrome (CCHS) is a rare disorder with failure of automatic control of breathing, defined by lack of an appropriate ventilatory response to hypercarbia and hypoxia. However, more detailed evaluation of cardiorespiratory coupling has not been previously performed in those with CCHS. We postulate that those with CCHS have disjointed cardiorespiratory responses to ventilatory challenges due to their alterations in sympathetic modulation. Therefore, we performed ventilatory rebreathing challenges with hypercarbia and hypoxia on 5 subjects with CCHS (age 21.2 plusmn 5.3 years; 3 females) and 7 controls (age 20.0 plusmn 4.0 years; 4 females). We measured breath-to-breath respiratory parameters (airflow, P_ETCO2, S_aO2), ECG, and continuous non-invasive blood pressure. As previously shown, when compared to controls CCHS subjects lacked ventilatory responses to isocapnic hypoxia (p=0.004) and hyperoxic hypercarbia (p=0.002). During hypercapnia, both control and CCHS subjects had similar rates of decrease in R-R intervals (RRI; slope -1.3plusmn2.5 vs. -1.4plusmn1.1, n.s.) and increase in beat-to-beat averaged blood pressure (MBP; slope 1.2plusmn0.3 vs. 0.4plusmn0.1, n.s.) as P_ETCO2 increased. During hypoxia, both control and CCHS groups had similar rates of decrease in RRI (slope 14.2plusmn3.0 vs. 7.5plusmn3.9, n.s.) and increase in MBP (slope -1.11plusmn1.12 vs. -0.9plusmn0.8, n.s.) as S_aO2 decreased. We conclude that despite having a markedly diminished ventilatory response to hypercarbia and hypoxia, subjects with CCHS have normal cardiovascular responses to these challenges. We speculate that this indicates that chemoreceptors are functional. Therefore the abnormality in ventilatory responses is located in the ventilatory controller