Induction of oscillatory ventilation pattern using dynamic modulation of heart rate through a pacemaker

For disease states characterized by oscillatory ventilation, an ideal dynamic therapy would apply a counteracting oscillation in ventilation. Modulating respiratory gas transport through the circulation might allow this. We explore the ability of repetitive alternations in heart rate, using a cardiac pacemaker, to elicit oscillations in respiratory variables and discuss the potential for therapeutic exploitation. By incorporating acute cardiac output manipulations into an integrated mathematical model, we observed that a rise in cardiac output should yield a gradual rise in end-tidal CO2 and, subsequently, ventilation. An alternating pattern of cardiac output might, therefore, create oscillations in CO2 and ventilation. We studied the effect of repeated alternations in heart rate of 30 beats/min with periodicity of 60 s, on cardiac output, respiratory gases, and ventilation in 22 subjects with implanted cardiac pacemakers and stable breathing patterns. End-tidal CO2 and ventilation developed consistent oscillations with a period of 60 s during the heart rate alternations, with mean peak-to-trough relative excursions of 8.4 +/- 5.0% (P < 0.0001) and 24.4 +/- 18.8% (P < 0.0001), respectively. Furthermore, we verified the mathematical prediction that the amplitude of these oscillations would depend on those in cardiac output (r = 0.59, P = 0.001). Repetitive alternations in heart rate can elicit reproducible oscillations in end-tidal CO2 and ventilation. The size of this effect depends on the magnitude of the cardiac output response. Harnessed and timed appropriately, this cardiorespiratory mechanism might be exploited to create an active dynamic responsive pacing algorithm to counteract spontaneous respiratory oscillations, such as those causing apneic breathing disorders.