Shanks Julia, Pachen Mridula, Lever Nigel A, Paton Julian F R, Ramchandra Rohit
Department of Physiology, Faculty of Medical and Health Sciences, Manaaki Manawa - The Centre for Heart Research, University of Auckland, 85 Park Road, Grafton, 1023, Auckland, New Zealand.
Department of Cardiology, Auckland City Hospital, Auckland District Health Board, Park Road, Grafton, Auckland, New Zealand.
Basic Res Cardiol. 2025 May 3. doi: 10.1007/s00395-025-01110-3.
Individuals with heart failure have significantly reduced exercise capacity, a critical life-limiting symptom for those living with the disease. Heart failure is negatively correlated with decreased heart rate variability, including the loss of heart rate variability in tune with breathing-termed respiratory heart rate variability (RespHRV). We tested the hypothesis that restoration of RespHRV would improve exercise tolerance. Heart failure was induced in adult female sheep using a microembolization technique, and the sheep were divided into two groups: RespHRV paced and monotonically paced. Following a 1-week baseline recording, the sheep underwent 2 weeks of pacing. Direct recordings of hemodynamic parameters, including arterial pressure, cardiac output, coronary artery blood flow, and heart rate, were taken at rest and during treadmill exercise. Reinstating RespHRV significantly increased resting cardiac output, a change not observed in monotonically paced sheep. Neither group showed a change in resting coronary artery blood flow. During exercise, RespHRV-paced sheep showed increased cardiac output, coronary artery blood flow, cardiac power output, and faster heart rate recovery post-exercise. In contrast, monotonically paced sheep showed no changes in exercise-induced cardiac function. A separate group of heart failure animals were studied to determine if these benefits would persist alongside heart failure medications. RespHRV pacing continued to improve resting cardiac output with concurrent heart failure medications. Our results indicate that reinstating RespHRV may be a novel approach for improving outcomes in heart failure, including exercise capacity.
心力衰竭患者的运动能力显著降低，这是该疾病患者的一个关键的限制生命的症状。心力衰竭与心率变异性降低呈负相关，包括与呼吸同步的心率变异性丧失，即呼吸性心率变异性（RespHRV）。我们检验了恢复RespHRV会改善运动耐量的假设。使用微栓塞技术在成年雌性绵羊中诱发心力衰竭，并将绵羊分为两组：RespHRV起搏组和单调起搏组。在进行1周的基线记录后，绵羊接受了2周的起搏。在休息和跑步机运动期间直接记录血流动力学参数，包括动脉压、心输出量、冠状动脉血流量和心率。恢复RespHRV显著增加了静息心输出量，而在单调起搏的绵羊中未观察到这种变化。两组的静息冠状动脉血流量均未显示变化。在运动期间，RespHRV起搏的绵羊心输出量增加、冠状动脉血流量增加、心脏功率输出增加，并且运动后心率恢复更快。相比之下，单调起搏的绵羊在运动诱导的心脏功能方面没有变化。对另一组心力衰竭动物进行了研究，以确定这些益处是否会在使用心力衰竭药物的同时持续存在。在使用同时期心力衰竭药物的情况下，RespHRV起搏继续改善静息心输出量。我们的结果表明，恢复RespHRV可能是改善心力衰竭患者预后（包括运动能力）的一种新方法。
