Evaluating the physiological significance of respiratory sinus arrhythmia: looking beyond ventilation–perfusion efficiency

Abstract

Key points• Respiratory sinus arrhythmia (RSA) is the variation of heart rate with breathing: heart rate increases during inspiration and decreases during expiration.• RSA is seen in many species including humans where it is strongest in the young and fit. The loss of RSA has been linked with cardiac mortality; however, the function of RSA is presently unknown.• One hypothesis proposed previously is that RSA allows for more efficient gas exchange between the lungs and the blood.• Our theoretical study does not support this hypothesis. Instead, a new hypothesis is proposed and tested using computational tools -that RSA helps the heart do less work while maintaining healthy levels of blood gases.• Of course, this new hypothesis needs to be further tested both experimentally and by using more sophisticated mathematical models, but if correct, it could explain why inducing RSA artificially in patients with cardiovascular disease improves their health.Abstract We conducted a theoretical study of the physiological significance of respiratory sinus arrhythmia (RSA), a phenomenon used as an index of cardiac vagal tone and wellbeing, whereby the heart rate (HR) increases during inspiration and decreases during expiration. We first tested the hypothesis that RSA improves gas exchange efficiency but found that although gas exchange efficiency improved with slow and deep breathing and with increased mean heart rate, this was unrelated to RSA. We then formulated and tested a new hypothesis: that RSA minimizes the work done by the heart while maintaining physiological levels of arterial carbon dioxide. We tested the new hypothesis using two methods. First, the HR for which the work is minimized was calculated using techniques from optimal control theory. This calculation was done on simplified models that we derived from a previously published model of gas exchange in mammals. We found that the calculated HR was remarkably similar to RSA and that this became more profound under slow and deep breathing. Second, the HR was prescribed and the work done by the heart was calculated by conducting a series of numerical experiments on the previously published gas exchange model. We found that cardiac work was minimized for RSA-like HR functions, most profoundly under slow and deep breathing. These findings provide novel insights into potential reasons for and benefits of RSA under physiological conditions.

Increased cardio-respiratory coupling evoked by slow deep breathing can persist in normal humans

“…Even though the data of Hayano and Yasuma (1996) are convincing, a computational model did not support this interpretation (Ben-Tal et al, 2012). Rather than benefitting gas exchange; modelling RSA supported a benefit for the heart (Ben-Tal et al, 2012).…”

“…Indeed, this concept was verified in a well-designed study performed in canines, where the RSA is dramatic compared to humans (Hayano et al, 1996). However, in a theoretical study using optimal control theory as well as a computational model of gas exchange, RSA minimized the cardiac work while maintaining physiological gas levels (Ben-Tal et al, 2012). While modelling did not support improve gas exchange efficiency, it supported CRC as physiologically significant and not simply an epiphenomenon, the appendix of homeostatic control.…”

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network

“…Furthermore, breathing, heart rate, and blood pressure show rhythmic interaction on multiple timescales: heartbeat to heartbeat, breath to breath, and in slow wave oscillations (i.e., Mayer waves) (Dick et al 2014;Morris et al 2010). Efficient coordination of the respiratory and cardiovascular systems lessens the physiological work load; for example, a recent computational study (Ben-Tal et al 2012) indicates that respiratory sinus arrhythmia minimizes the work done by the heart while maintaining healthy blood gas levels. Current simulations are accomplished with a hybrid stochastic/mechanistic model: networks of integrate-and-fire neurons with connectivity derived from the study of multineuron recordings generate output that drives a biomechanical model of the respiratory muscles, airway, and lungs developed with published measures from human subjects .…”

Modulation of respiratory sinus arrhythmia in rats with central pattern generator hardware

“…The brainstem central pattern generator is known to couple the rate of respiration to the heartbeat with the effect of making the heartbeat faster during inspiration than during expiration. This phenomenon known as respiratory sinus arrhythmia (RSA) is believed to increase blood pumping efficiency and save cardiac energy (Abdala et al, 2009;Baekey et al, 2010;Ben-Tal et al, 2012;Champagnat et al, 2009;Fortuna et al, 2008;Nicholls and Paton, 2009). Respiratory sinus arrhythmia is lost in heart failure and hypertension and is a prognostic indicator for sudden cardiac death (Mortara et al, 1994).…”