Muscle metaboreflex-induced increases in effective arterial elastance: effect of heart failure

Abstract

Dynamic exercise elicits robust changes in sympathetic activity in part due to accumulation of metabolites within the active skeletal muscle which activates group III and IV afferents triggering the muscle metaboreflex. This reflex raises cardiac output via tachycardia, increased ventricular contractility, and central blood volume mobilization which improves perfusion to the active skeletal muscle. An important component of maintaining exercise performance is optimal ventricular ‐ vascular coupling which can change with exercise, aging, as well as pathophysiological conditions. The effect of muscle metaboreflex activation (MMA) on ventricular ‐ vascular interactions is unknown. We hypothesized that MMA increases Effective Arterial Elastance (Ea). We utilized two previously published methods of evaluating Ea (End Systolic Pressure / Stroke Volume (M1) and Heart Rate x Vascular Resistance (M2)) at rest, during mild treadmill exercise, and during MMA induced via partial reductions in hindlimb blood flow imposed during exercise. At rest Ea averaged 3.0 ± 0.1 and 3.0 ± 0.2 mmHg/mL for M1 and M2, respectively. With the transition from rest to mild exercise little change in Ea occurred, whereas with subsequent MMA, Ea increased significantly by 33.6% ± 2.7 and 20.5% ± 2.3 for M1 and M2. We conclude that MMA elicits robust increases in Ea which parallel the substantial increases in ventricular performance thereby optimizing ventricular ‐ vascular coupling. Support or Funding Information Supported by HL‐55473, HL‐126706, HL120822 and R25 GM058905 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ventricular contraction and relaxation rates during muscle metaboreflex activation in heart failure: are they coupled?

“…After blockade of α‐adrenergic receptors, this coronary vasoconstriction is reversed to coronary vasodilatation during metaboreflex activation, and coronary blood flow increases substantially and there are significant improvements in ventricular function (Coutsos et al., 2010, 2013). Furthermore, we have shown that ventricular–vascular coupling is also markedly altered in heart failure as much greater increases in arterial elastance occurs which are unaccompanied by increases in ventricular elastance thereby further uncoupling an already impaired ventricular–vascular relationship (Mannozzi et al., 2020). The higher the arterial elastance the less effective energy transfer becomes, and this in turn reduces the ability to improve stroke work.…”

“…During mild exercise (3.2 km h −1 0% grade) increases in ventricular function (d P /d t MAX and d P /d t MIN ) in response to the exercise itself are small. However, the level of increase is not uniform and these small increases in ventricular function do not always reach statistical significance (Kaur et al., 2018; Mannozzi et al., 2020). During muscle metaboreflex activation at mild workload, sympathetic drive to the heart is substantially increased causing highly significant large increases in ventricular function.…”

“…Wyss, Ardell, Scher, & Rowell (1983) showed that there was no significant difference in the haemodynamic responses observed during graded vs. single step reductions regardless of workload). After control experiments were performed in all 14 animals, the ventricular pacing leads were connected to a pacemaker for rapid ventricular pacing (200-240 bpm, ∼30 days) to achieve heart failure with reduced ejection fraction as described in previous studies (Ansorge et al, 2005;Coutsos et al, 2013;Hammond et al, 2000;Kaur et al, 2017;Mannozzi et al, 2020;O'Leary et al, 2004O'Leary et al, , 2019Sala-Mercado et al, 2007). Heart failure was indicated by frank reduction in ventricular performance and was apparent when the pacemaker was disconnected, e.g.…”

Chronic ablation of TRPV1-sensitive skeletal muscle afferents attenuates the muscle metaboreflex

“…Even in normal subjects this reflex is thought to become tonically active at relatively modest workloads and activation of this reflex can cause substantial increases in sympathetic activity, which elicits increases in cardiac output via tachycardia, increased ventricular contractility, and central blood volume mobilization (5-7, 9-13, 34-41). Arterial elastance rises in parallel with ventricular maximal elastance, thereby optimizing ventricular-vascular coupling and energy transfer from the left ventricle to the systemic circulation (11,42,43). Peripheral vasoconstriction can also occur which is countered by adrenal epinephrine release and b 2 -mediated vasodilation (16,34,38,40).…”

Predictive value of change in effective arterial elastance in norepinephrine weaning: a retrospective study

“…However, the baseline value of Ea differed in previous studies due to the different measurements given (19,24,25). Moreover, recent studies reported that a higher Ea dyn might indicate greater efficiency of the cardiovascular system in delivering energy to the arterial system for sustaining blood flow (35,36). Based on this, we were only able to suggest that a higher pre-infusion Ea might indicate a positive preload response to fluid challenge, without using an accurate predictive value.…”