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

Abstract

New findings: What is the central question of this study? Does the muscle metaboreflex affect the ratio of left ventricular contraction/relaxation rates and does heart failure impact this relationship. What is the main finding and its importance? The effect of muscle metaboreflex activation on the ventricular relaxation rate was significantly attenuated in heart failure. Heart failure attenuates the exercise and muscle metaboreflex-induced changes in the contraction/relaxation ratio. In heart failure, the reduced ability to raise cardiac output during muscle metaboreflex activation may not solely be due to attenuation of ventricular contraction but also alterations in ventricular relaxation and diastolic function.

Abstract: The relationship between contraction and relaxation rates of the left ventricle varies with exercise. In in vitro models, this ratio was shown to be relatively unaltered by changes in sarcomere length, frequency of stimulation, and β-adrenergic stimulation. We investigated whether the ratio of contraction to relaxation rate is maintained in the whole heart during exercise and muscle metaboreflex activation and whether heart failure alters these relationships. We observed that in healthy subjects the ratio of contraction to relaxation increases from rest to exercise as a result of a higher increase in contraction relative to relaxation. During muscle metaboreflex activation the ratio of contraction to relaxation is significantly reduced towards 1.0 due to a large increase in relaxation rate matching contraction rate. In heart failure, contraction and relaxation rates are significantly reduced, and increases during exercise are attenuated. A significant increase in the ratio was observed from rest to exercise although baseline ratio values were significantly reduced close to 1.0 when compared to healthy subjects. There was no significant change observed between exercise and muscle metaboreflex activation nor was the ratio during muscle metaboreflex activation significantly different between heart failure and control. We conclude that heart failure reduces the muscle metaboreflex gain and contraction and relaxation rates. Furthermore, we observed that the ratio of the contraction and relaxation rates during muscle metaboreflex activation is not significantly different between control and heart failure, but significant changes in the ratio in healthy subjects due to increased relaxation rate were abolished in heart failure.

Keywords: contraction; diastolic function; heart failure; metaboreflex; relaxation.

FIGURE 1:

Average one-minute steady state hemodynamic values taken at rest (REST), exercise (3.2 km/h 0% grade) (EX), and exercise with muscle metaboreflex activation (MMA) before (white) and after induction of heart failure via rapid ventricular pacing (gray). Standard deviation is shown on the bar graphs. Statistical significance against previous workload is shown as * P < 0.05. Comparisons between control and heart failure for a given workload shown as † P < 0.05. (N=14).

FIGURE 2:

Left average 1-minute steady state values of dP/dt _MAX and _MIN taken at rest (REST), exercise (3.2 km/h 0% grade) (EX), and exercise with muscle metaboreflex activation (MMA) before (white) and after induction of heart failure via rapid ventricular pacing (gray). Right shows the average change from EX to MMA in control and heart failure. Standard deviation is shown on the bar graphs. Statistical significance against previous workload is shown as * P < 0.05. Comparisons between control and heart failure for a given workload or change from previous workload shown as † P < 0.05. (N=14).

FIGURE 3:

(Left) Line graph representation of the change in the slope of dP/dts before (solid circles) and after induction of heart failure via rapid ventricular pacing (open circles) should be observed from the right point (exercise) to the middle point (reflex threshold) to the final point left (peak muscle metaboreflex activation) as hindlimb blood flow is reduced. (Right) Assessment of muscle metaboreflex gain as judged by the slope of the line from threshold to maximal muscle metaboreflex activation before (white bars) and after induction of heart failure via rapid ventricular pacing (grey bars). Statistical significance between control and heart failure shown as † P < 0.05. (N=7).

FIGURE 4:

Average one-minute steady state values of the ratio of dP/dt _MAX divided by dP/dt _MIN taken at rest (REST), exercise (3.2 km/h 0% grade) (EX), and exercise with muscle metaboreflex activation (MMA) before (white) and after induction of heart failure via rapid ventricular pacing (gray). Right shows the average change from EX to MMA in control and heart failure. Standard deviation is shown on the bar graphs. Statistical significance against previous workload is shown as * P < 0.05. Comparisons between control and heart failure for a given workload or change from previous workload shown as † P < 0.05. (N=14).