Novel cardiac pacemaker-based human model of periodic breathing to develop real-time, pre-emptive technology for carbon dioxide stabilisation

Background Constant flow and concentration CO 2 has previously been efficacious in attenuating ventilatory oscillations in periodic breathing (PB) where oscillations in CO 2 drive ventilatory oscillations. However, it has the undesirable effect of increasing end-tidal CO 2 , and ventilation. We tested, in a model of PB, a dynamic CO 2 therapy that aims to attenuate pacemaker-induced ventilatory oscillations while minimising CO 2 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 CO 2 administration, and tested different timings. Results We found that cardiac output alternation using pacemakers successfully induced PB. Dynamic CO 2 therapy, when delivered coincident with hyperventilation, attenuated 57% of the experimentally induced oscillations in end-tidal CO 2 : SD/mean 0.06±0.01 untreated versus 0.04±0.01 with treatment (p 2 did not significantly rise when dynamic CO 2 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 CO 2 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 CO 2 coincident with hyperventilation, ventilatory oscillations can be substantially attenuated without a significant increase in end-tidal CO 2 or ventilation. Dynamic CO 2 administration might be developed into a clinical treatment for PB. Trial Registration number ISRCTN29344450.