Arterial Baroreflex Inhibits Muscle Metaboreflex Induced Increases in Effective Arterial Elastance: Implications for Ventricular-Vascular Coupling

Abstract

The ventricular-vascular relationship assesses the efficacy of energy transferred from the left ventricle to the systemic circulation and is quantified as the ratio of effective arterial elastance to maximal left ventricular elastance. This relationship is maintained during exercise via reflex increases in cardiovascular performance raising both arterial and ventricular elastance in parallel. These changes are, in part, due to reflexes engendered by activation of metabosensitive skeletal muscle afferents-termed the muscle metaboreflex. However, in heart failure, ventricular-vascular uncoupling is apparent and muscle metaboreflex activation worsens this relationship through enhanced systemic vasoconstriction markedly increasing effective arterial elastance which is unaccompanied by substantial increases in ventricular function. This enhanced arterial vasoconstriction is, in part, due to significant reductions in cardiac performance induced by heart failure causing over-stimulation of the metaboreflex due to under perfusion of active skeletal muscle, but also as a result of reduced baroreflex buffering of the muscle metaboreflex-induced peripheral sympatho-activation. To what extent the arterial baroreflex modifies the metaboreflex-induced changes in effective arterial elastance is unknown. We investigated in chronically instrumented conscious canines if removal of baroreflex input via sino-aortic baroreceptor denervation (SAD) would significantly enhance effective arterial elastance in normal animals and whether this would be amplified after induction of heart failure. We observed that effective arterial elastance (E_a), was significantly increased during muscle metaboreflex activation after SAD (0.4 ± 0.1 mmHg/mL to 1.4 ± 0.3 mmHg/mL). In heart failure, metaboreflex activation caused exaggerated increases in E_a and in this setting, SAD significantly increased the rise in E_a elicited by muscle metaboreflex activation (1.3 ± 0.3 mmHg/mL to 2.3 ± 0.3 mmHg/mL). Thus, we conclude that the arterial baroreflex does buffer muscle metaboreflex induced increases in E_a and this buffering likely has effects on the ventricular-vascular coupling.

Keywords: arterial baroreflex; effective arterial elastance (Ea); muscle metaboreflex activation; neural control of cardiovascular system; ventricular vascular coupling.

FIGURE 1

Average 1-min steady state hemodynamics from the Control_group at rest, exercise (EX), and exercise with muscle metaboreflex activation (MMA) before (white) and after induction of heart failure (gray). Data are reported as means with standard error. Observed data points are overlain on corresponding bar graphs. Statistical significance vs. previous workload is depicted as * and vs. previous condition as ^† where P < 0.05. (N = 5).

FIGURE 2

Average 1-min steady state hemodynamics from the SAD_group at rest, exercise (EX), and exercise with muscle metaboreflex activation (MMA) before (white) an after SAD (orange) and after induction of heart failure post SAD (red). Data are reported as means with standard error. Observed data points are overlain on corresponding bar graphs. Statistical significance vs. previous workload depicted as * where P < 0.05. Comparisons of the condition of SAD vs. control depicted as ^† where P < 0.05. Comparisons of the condition of heart failure vs. SAD depicted as ^‡ where P < 0.05. (N = 5).

FIGURE 3

(A) Average 1-min steady state values of Effective Arterial Elastance and Stroke Work in the Control_group at rest, exercise (EX), and exercise with muscle metaboreflex activation (MMA) before (white) and after induction of heart failure (gray). Statistical significance vs. previous workload depicted * and vs. previous condition as ^† where P < 0.05. (N = 5). (B) Average 1-min steady state values of Effective Arterial Elastance and Stroke Work in the SAD_group at res, exercise (EX), and exercise with muscle metaboreflex activation (MMA) before (white) and after SAD (orange), and after heart failure induction post SAD (red). Statistical significance vs. previous workload depicted as * where P < 0.05. Comparisons of the condition of SAD vs. control depicted as ^† where P < 0.05. Comparisons of the condition of heart failure vs. SAD depicted as ^‡ where P < 0.05. (N = 5) Data for (A,B) are reported as means with standard error. Observed data points are overlain on corresponding bar graphs.

FIGURE 4

(A) The relative change in Effective Arterial Elastance and Stroke Work in the transition from exercise to exercise with muscle metaboreflex activation before (white) and after induction of heart failure (gray) in the Control_group. (B) The relative change in Effective Arterial Elastance and Stroke Work in the transition from exercise to exercise with muscle metaboreflex activation before (white) and after SAD (gray) in the SAD_group. (C) The relative change in Effective Arterial Elastance and Stroke Work in the transition from exercise to exercise with muscle metaboreflex activation in normal animals with SAD (white) and after induction of heart failure post SAD (gray) in the SAD_group. (D) The relative change in Effective Arterial Elastance and Stroke Work in the transition from exercise to exercise with muscle metaboreflex activation in heart failure animals from the Control_group (white) and heart failure animals post SAD from the SAD_group (gray). For all panels data are reported as means with standard error where data points are overlain on corresponding bar graphs. Statistical significance vs. the previous state as ^†where P < 0.05. An N = 5 was used for each bar graph in every panel.

FIGURE 5

(A) Average 1-min steady state values of central venous pressure from the Control_group at rest, exercise (EX), and exercise with muscle metaboreflex activation (MMA) before (white) and after induction of heart failure (gray). Data are reported as means with standard error. Observed data points are overlain on corresponding bar graphs. Statistical significance vs. previous workload is depicted as * and vs. previous condition as ^† where P < 0.05. (N = 5). (B) Average 1-min steady state values of central venous pressure from the SAD_group at rest, exercise (EX), and exercise with muscle metaboreflex activation (MMA) after SAD (orange) and after induction of heart failure post SAD (red). Data are reported as means with standard error. Observed data points are overlain on corresponding bar graphs. Statistical significance vs. previous workload depicted as * where P < 0.05. Comparisons of the condition of SAD vs. Heart failure SAD depicted as ^‡ where P < 0.05. (N = 5).

FIGURE 6

Relationship between ventricular maximal elastance (Emax) and stroke work before (black circles) and after induction of heart failure (white circles) at rest, mild exercise, and muscle metaboreflex activation. A linear regression (dotted line) was performed on these points. and the R₂ value are shown on the plot. Error bars depict standard error of the mean in both directions (Data points were calculated from primary data collected in experiments which were reported in Coutsos et al. (2010, 2013) (N = 6).