Arterial Baroreceptor Denervation Enhances Muscle Metaboreflex Induced Increases in Effective Arterial Elastance Without Worsening Stoke Work During Dynamic Exercise in Heart Failure

Abstract

Optimal energy transfer from the left ventricle to the systemic circulation is paramount to the maintenance of workload performance during exercise. This interaction between the heart and circulation is quantified by the ventricular‐vascular coupling relationship which is the ratio of direct assessments of arterial and ventricular elastance. During exercise, increases in both arterial and ventricular elastance occur as a result of sympatho‐excitatory efferent responses brought about by activation of metabosensitive skeletal muscle afferents ‐ termed the muscle metaboreflex. In heart failure, ventricular elastance is reduced and arterial elastance is increased causing ventricular‐vascular uncoupling at rest and further sympatho‐activation elicited by the muscle metaboreflex worsens this relationship through profound systemic vasoconstriction. Recent studies have concluded that the arterial baroreflex substantially buffers vasoconstriction within peripheral vascular beds. In heart failure, the arterial baroreflex buffering capacity is significantly reduced and muscle metaboreflex induced vasoconstriction is enhanced. To what extent this shift in metaboreflex control of peripheral sympathetic tone affects ventricular‐vascular coupling is unknown. We examined the effect of sino‐aortic baroreceptor denervation (SAD) on the ventricular‐vascular relationship at rest and during moderate dynamic exercise (6.4 km/h 10% grade) in chronically instrument conscious canines before and after the induction of heart failure to determine whether loss of baroreflex buffering engendered further uncoupling of the ventricular‐vascular relationship in heart failure. Increases in effective arterial elastance (Ea), were significantly enhanced during muscle metaboreflex activation after SAD (0.5 ± 0.1 mmHg/ml to 2.0 ± 0.4 mmHg/mL). Furthermore, SAD elicited a significant increase in the ability to improve stroke work during muscle metaboreflex activation (2.7 ± 0.1 L*mmHg to 3.5 ± 0.1 L*mmHg) suggesting that even without the arterial baroreflex muscle metaboreflex activation in healthy subjects maintains ventricular‐vascular coupling. In heart failure, SAD elicited a 2‐fold increase in Ea during muscle metaboreflex activation (0.9 ± 0.2 mmHg/ml to 1.8 ± 0.2 mmHg/ml). Stroke work did not improve during muscle metaboreflex activation in heart failure with SAD. Thus, enhanced increases in Ea are likely not matched by ventricular elastance thereby exacerbating the already uncoupled ventricular‐vascular relationship. We conclude that the arterial baroreflex actively restrains increases in Ea and stroke work during muscle metaboreflex activation and SAD does not appear to significantly impact the ventricular‐vascular relationship in healthy subjects. In heart failure, the arterial baroreflex retains some degree of restraint over metaboreflex induced increases in Ea and thus is likely a mechanism which prevents worsening of the already impaired energy transfer from the left ventricle to the systemic circulation.