Respiratory system stability and abnormal carbon dioxide homeostasis

Area of Science:

• Physiology
• Respiratory Control
• Cardiovascular System

Background:

• Breathing patterns during sleep can become unstable, particularly in conditions like familial dysautonomia (FD) and congenital central hypoventilation syndrome (CCHS).
• The respiratory CO2 feedback control system's loop gain (LG) is a critical factor influencing breathing stability.

Purpose of the Study:

• To test the hypothesis that interactions among eight parameters determine respiratory loop gain (LG).
• To investigate how LG influences breathing stability in healthy sleepers, FD patients, and CCHS patients.
• To assess the predictability of breathing cycle duration.

Main Methods:

• Measured CO2 sensitivity, CO2 delivery capacity, circulation delay, mean lung volume, and mixed venous PCO2 in 8 FD patients, 2 CCHS patients, and 19 healthy controls.
• Utilized a mathematical model to compute LG during sleep for each respiration epoch.
• Quantified ventilatory oscillations (R) using power density spectra under varying inspiratory O2 concentrations (FIO2).

Main Results:

• In 2 FD patients, elevated LG and periodic breathing were observed, linked to elevated mixed venous PCO2 and reduced CO2 delivery capacity.
• High LG and unstable breathing in some healthy volunteers correlated with high chemosensitivity.
• CCHS patients maintained stable breathing even at 0.12 FIO2 due to near-zero LG resulting from lack of chemosensitivity.

Conclusions:

• Interactions among respiratory and cardiovascular parameters significantly influence respiratory control loop gain (LG) and breathing stability during sleep.
• Abnormalities in mixed venous PCO2 and CO2 delivery capacity can lead to elevated LG and instability in FD patients.
• CCHS patients exhibit inherent stability due to a lack of chemosensitivity, resulting in minimal LG.