A rhythm for saving life? Respiratory sinus arrhythmia improves cardiac function in rat heart failure

Respiratory sinus arrhythmia (RSA) is a physiological phenomenon by which heart rate (HR) is modulated by respiration. Absence of RSA is prognostic for cardiovascular disease, including heart failure. The physiological significance of RSA in health is controversial and unknown in disease. However, a recent modelling study predicted that RSA would improve cardiac efficiency. Thus, in a rat model of heart failure we tested whether reinstating RSA would improve cardiac function beyond monotonic pacing, which is currently used clinically. We designed and fabricated a novel biofeedback pacemaker (central pattern generator, CPG) that modulates HR every breath. By detecting diaphragmatic electromyographic activity the CPG dynamically drives pacing pulses to increase/decrease HR with inspiration/expiration, respectively. Myocardial infarction (MI) was performed on 8 adult male Wistar rats (290±10g) by permanent ligation of the left ascending coronary artery. One week post-MI, rats with an ejection fraction <50% (determined by echocardiography) were anaesthetised and electrodes surgically implanted to record the diaphragmatic electromyographic activity and electrocardiogram; electrodes were also sutured to the right atrium for sino-atrial node pacing. Four weeks post-MI, rats were divided into 3 groups: respiratory-modulated pacing using the CPG; monotonic pacing at matched average HR, and no pacing. Pacing was for 8h per day for 2 weeks. Transthoracic echocardiography quantified left ventricular cardiac function before/after cardiac pacing. Pacing was effectively delivered for 46±8 and 50±3 % of the time for respiratory-modulated and monotonic pacing, respectively (NS). Mean paced HR for respiratory-modulated and monotonic pacing was similar (401±6 v 408±13 bpm, respectively; P>0.05) whereas the standard deviation of HR within-animals was greatest in respiratory modulated paced rats (18±4 v 1±0; n=5, P<0.05). With pacing switched-off, stroke volume index (P<0.05), stroke volume (P=0.07) and cardiac output (16±6%; P=0.07) were all higher with respiratory-modulated than monotonic pacing or no pacing. Chronic respiratory modulation of HR appears to instil plasticity that improves cardiac function in a rat model of left ventricular dysfunction. This study provides the first evidence to support a physiological benefit of incorporating RSA into future pacemakers for human patients with heart failure. BHF funded research