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

Abstract

Dynamic exercise elicits robust increases in sympathetic activity in part due to muscle metaboreflex activation (MMA), a pressor response triggered by activation of skeletal muscle afferents. MMA during dynamic exercise increases arterial pressure by increasing cardiac output via increases in heart rate, ventricular contractility, and central blood volume mobilization. In heart failure, ventricular function is compromised, and MMA elicits peripheral vasoconstriction. Ventricular-vascular coupling reflects the efficiency of energy transfer from the left ventricle to the systemic circulation and is calculated as the ratio of effective arterial elastance (E_a) to left ventricular maximal elastance (E_max). The effect of MMA on E_a in normal subjects is unknown. Furthermore, whether muscle metaboreflex control of E_a is altered in heart failure has not been investigated. We utilized two previously published methods of evaluating E_a [end-systolic pressure/stroke volume (E_aPV)] and [heart rate × vascular resistance (E_aZ)] during rest, mild treadmill exercise, and MMA (induced via partial reductions in hindlimb blood flow imposed during exercise) in chronically instrumented conscious canines before and after induction of heart failure via rapid ventricular pacing. In healthy animals, MMA elicits significant increases in effective arterial elastance and stroke work that likely maintains ventricular-vascular coupling. In heart failure, E_a is high, and MMA-induced increases are exaggerated, which further exacerbates the already uncoupled ventricular-vascular relationship, which likely contributes to the impaired ability to raise stroke work and cardiac output during exercise in heart failure.

Keywords: exercise pressor reflex; heart failure; stroke work; vascular function; ventricular function.

Fig. 1.

Average 1-min steady-state values of cardiac output, mean arterial pressure, end-systolic pressure, stroke volume, heart rate, and nonischemic vascular resistance at rest (REST), during free-flow mild exercise (EX), and EX with muscle metaboreflex activation (EX + MMA) induced by graded reductions in hindlimb blood flow of 50–60% before (white bars) and after induction of heart failure (gray bars). Standard error is shown on bar graphs with individual data points overlaid. Statistical significance compared with the previous setting is shown as *P < 0.05. Comparisons between control and heart failure within each setting are shown as †P < 0.05. (N = 5 canines).

Fig. 2.

A: average 1-min steady-state indexes and effective arterial elastance derived from traditional pressure-volume (PV) loop calculation (E_aPV, end-systolic pressure divided by stroke volume) and from vascular components (E_aZ, heart rate multiplied by nonischemic vascular resistance). Mean values are shown at rest (REST), during free-flow mild exercise (EX), and EX with muscle metaboreflex activation (EX + MMA) induced by graded reductions in hindlimb blood flow of 50–60% before (white bars) and after induction of heart failure (gray bars). B: average changes between 1-min steady-state values during exercise and exercise with MMA. Standard error is shown on bar graphs, and individual data points are plotted. Statistical significance between successive settings is shown as *P < 0.05. Comparisons between control and heart failure are shown as †P < 0.05. (N = canines).

Fig. 3.

A: average 1-min steady-state indexes of ventricular function dP/dt_MAX and dP/dt_MIN taken from the first derivative of the left ventricular pressure wave. Mean values are shown at rest (REST), during free-flow mild exercise (EX), and EX with muscle metaboreflex activation (EX + MMA) induced by graded reductions in hindlimb blood flow of 50–60% before (white bars) and after induction of heart failure (gray bars). B: average changes between 1-min steady-state values during exercise and exercise with MMA. Standard error is shown on bar graphs, and individual data points are plotted. Statistical significance between successive settings is shown as *P < 0.05. Comparisons between control and heart failure are shown as †P < 0.05. (N = 5).

Fig. 4.

Bland-Altman plot evaluating the agreement between E_aPV (end-systolic pressure divided by stroke volume) and E_aZ (heart rate multiplied by nonischemic vascular resistance) before (filled) and after induction of heart failure (open) during rest (squares), free flow exercise (triangles), and exercise with peak muscle metaboreflex activation (circles). Dashed lines indicate upper and lower limits of agreement, and the solid line indicates bias. (N = 5 canines).