Origin of oscillatory kinetics of respiratory gas exchange in chronic heart failure

Abstract

Background - Respiratory gas exchange measurements in patients with chronic heart failure (CHF) at rest and during exercise commonly reveal prominent slow oscillations in ventilation (V(E)), measured oxygen uptake (VO2), and carbon dioxide production (VCO2), whose origin is not clear. Voluntary simulation of periodic breathing (PB) in normals has been reported to generate a different pattern of oscillations in gas exchange from that seen in spontaneous PB. This necessitates hypothesizing that PB is caused by a primary oscillation in tissue metabolism or in cardiac output. Methods and Results - We developed an automated method by which normal controls could be guided to breathe according to a PB pattern. The resultant metabolic oscillations closely matched those seen in spontaneous PB and had several interesting properties. At low workloads (including rest), the oscillations in VO2 were as prominent as those in V(E) in both spontaneous PB (α(VO2)/α(VE)=0.92 ± 0.04) and voluntary PB-(0.93 ± 0.07). However, at increased workload, the oscillations in Vo2 because less prominent than those in V(E) in spontaneous PB (intermediate workload 0.63 ± 0.05, high workload 0.57 ± 0.04; P<0.001) and voluntary PB (intermediate 0.66 ± 0.03, high 0.48 ± 0.03; P<0.001). There was no difference in the relative size of metabolic oscillations between voluntary and spontaneous PB at matched workloads (P>0.05 at low, intermediate, and high workloads). Furthermore, Vo2 peaked before V(E) in both spontaneous and voluntary PB. This time delay varied from 6.4 ± 0.4 s at low ventilation, to 11.3 ± 0.9 s at high ventilation (P<0.0001). Conclusions - The magnitude and phase pattern of oscillations in gas exchange of spontaneous PB can be obtained by adequately matched voluntary PB. Therefore, the gas exchange features of PB are explicable by primary ventilatory oscillation.