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<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 CO(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.