Sensitized Central Controller of Ventilation in Rats with Chronic Heart Failure Contributes to Hyperpnea Little at Rest but More during Exercise

To understand the pathophysiologic basis of exercise hyperpnea in chronic heart failure (CHF), we have developed an experimental method quantitatively characterizing ventilatory regulation system in rats. An equilibrium diagram illustrates the characteristics of two subsystems, i.e., the central controller (arterial CO₂ tension [Pa_CO2] to minute ventilation [V_E] relationship) and peripheral plant (V_E to Pa_CO2 relationship). In this study, we compared these between normal and CHF rats at rest. In anesthetized 6 postinfarction CHF rats and 6 normal rats, we induced hypercapnia by changing inspiratory CO₂ fraction and measured the steady-state Pa_CO2 to V_E relation. We altered V_E by varying the level of artificial ventilation and measured the V_E to Pa_CO2 relation. Central controller gain S was significantly lager in CHF rats, confirming clinical observation. The V_E at rest (operating point) in CHF was 24% larger; central hypersensitivity, however, contributed little (6%) to this increase. Central hypersensitivity alone would not explain hyperpnea at rest in CHF rats. Considering the right and upward shift of V_E to Pa_CO2 relation, central hypersensitivity contributes more to hyperpnea during exercise. The potential difference between normal and CHF rats in exercise-induced changes in controller and plant should be examined to fully understand the mechanism of exercise hyperpnea and to develop a method to attenuate this