Background Constant flow and concentration CO₂ has previously been efficacious in attenuating ventilatory oscillations in periodic breathing (PB) where oscillations in CO₂ drive ventilatory oscillations. However, it has the undesirable effect of increasing end-tidal CO₂, and ventilation. We tested, in a model of PB, a dynamic CO₂ therapy that aims to attenuate pacemaker-induced ventilatory oscillations while minimising CO₂ dose.

Methods First, pacemakers were manipulated in 12 pacemaker recipients, 6 with heart failure (ejection fraction (EF)=23.7±7.3%) and 6 without heart failure, to experimentally induce PB. Second, we applied a real-time algorithm of pre-emptive dynamic exogenous CO₂ administration, and tested different timings.

Results We found that cardiac output alternation using pacemakers successfully induced PB. Dynamic CO₂ therapy, when delivered coincident with hyperventilation, attenuated 57% of the experimentally induced oscillations in end-tidal CO₂: SD/mean 0.06±0.01 untreated versus 0.04±0.01 with treatment (p<0.0001) and 0.02±0.01 in baseline non-modified breathing. This translated to a 56% reduction in induced ventilatory oscillations: SD/mean 0.19±0.09 untreated versus 0.14±0.06 with treatment (p=0.001) and 0.10±0.03 at baseline. Of note, end-tidal CO₂ did not significantly rise when dynamic CO₂ was applied to the model (4.84±0.47 vs 4.91± 0.45 kPa, p=0.08). Furthermore, mean ventilation was also not significantly increased by dynamic CO₂ compared with untreated (7.8±1.2 vs 8.4±1.2 L/min, p=0.17).

Conclusions Cardiac pacemaker manipulation can be used to induce PB experimentally. In this induced PB, delivering CO₂ coincident with hyperventilation, ventilatory oscillations can be substantially attenuated without a significant increase in end-tidal CO₂ or ventilation. Dynamic CO₂ administration might be developed into a clinical treatment for PB.

Trial Registration number ISRCTN29344450.