Orthostatic modification of ventilatory dynamic response to carbon dioxide perturbations.

In order to determine whether changes in ventilatory control contribute to the observed decrease in arterial partial pressure of carbon dioxide (PaCO(2)) during head up tilt, we assessed ventilatory dynamic sensitivity to changes in PaCO(2) during supine and 70 degrees passive head up tilt. In 24 adult normals, we stimulated the ventilatory control system by switching inspired CO(2) between room air and room air+5% CO(2) in a pseudo random binary sequence. A Box-Jenkins model was used to compute ventilatory response to CO(2). Airflow, CO(2), non-invasive beat by beat blood pressure, ECG and cerebral blood flow velocity (Doppler) were recorded. During tilt, sensitivity of the ventilatory controller to CO(2) disturbance increased (from 0.45 to 0.72 L/min/mm Hg, p<0.005); minute ventilation increased (7.63 to 8.47 L/min, p<0.01), end tidal CO(2) (ETCO(2)), cerebral blood flow velocity (CBF) and baroreflex sensitivity decreased (46.9 to 42.9 mm Hg, p<0.001; 84.9 to 72.9 cm/s, p<0.001; and 17.6 to 5.5 ms/mm Hg, p<0.001). The primary observation from our study was that the sensitivity of ventilatory control system to perturbations in ETCO(2) increased during tilt. Taken together with decrease in mean levels of ETCO(2) and an increase in minute ventilation, these results suggest that during tilt, a change in the regulated level or 'set point' of PaCO(2) may occur.

Assessment of ventilatory sensitivity to carbon dioxide changes during orthostasis.

Investigators have anecdotally reported changes in respiratory pattern preceding symptoms of orthostatic intolerance for several years. Evidence from recent studies support these observations, and show that alterations in respiration often precede pre-syncope during orthostasis. These observations suggest the possibility that changes in interaction between the chemo and baro-reflex control systems may produce phasic or dynamic changes in respiratory and hemodynamic parameters such that these changes are important in orthostasis intolerance. Our objective in the present study was to develop a method to obtain a quantitative index of ventilatory sensitivity to changes in inspired during orthostasis. Based on an approach previously developed by one of the authors (EB), we used, during supine and 70 degrees head up tilt, pseudo-random binary changes in inspired CO2 to quantify ventilatory sensitivity to CO2 disturbances. A pneumotach was used to measure airflow. From these recordings, we used a prediction error based systems identification algorithm to quantify ventilatory impulse response to CO2 stimulus. Results from 7 subjects showed that the integrated ventilatory response (area under impulse response curve) to CO2 was larger during tilt than that during supine (mean [std] 5.3 [2.6] Vs 3.0 [1.6] ml/min/0.01LCO2). These results suggest that the changes in ventilation due to disturbances in CO2 are likely to be larger during orthostasis than those during supine. Such an elevated response would indicate that the role of chemo-reflex control of breathing in cardiovascular instability culminating in orthostatic intolerance is likely to be important and should be further investigated.