Muscle sympathetic nerve activity and ventilation during exercise in subjects with and without chronic heart failure

Abstract

Background: Changes within skeletal muscle, including augmentation of its capacity to elicit reflex increases in both efferent muscle sympathetic nerve activity (MSNA) and ventilation during work, contribute significantly to exercise intolerance in heart failure (HF). Previously, we demonstrated that peak oxygen uptake (pVO(2)) in HF relates inversely to MSNA at rest and during exercise.

Objective: To test the hypothesis that there is an independent positive relationship between resting MSNA and the ratio of ventilation to carbon dioxide output during exercise (VE/VCO(2)) that is augmented in HF.

Methods: MSNA at rest and VE/VCO(2)) during stationary cycling were measured in 30 patients (27 men) with HF (mean +/- SD ejection fraction 20+/-6%) and in 31 age-matched controls (29 men).

Results: MSNA was higher in HF patients than in controls (51.5+/-14.3 bursts/min versus 33.0+/-11.1 bursts/min; P<0.0001). The VE/VCO(2) slope was also higher in HF patients than in controls (33.7+/-5.7 versus 26.0+/-3.5; P<0.0001), whereas pVO(2) was lower in HF patients than in controls (18.6+/-6.6 versus 31.4+/-8.4 mL/kg/min; P<0.0001). There were significant relationships between MSNA and VE/VCO(2) in both HF (r=0.50; P=0.005) and control subjects (r=0.36; P=0.046). The slope of this regression equation was steeper in HF (0.20 versus 0.11 x MSNA; P=0.001). An analysis of covariance for main effects, including age and pVO(2), identified a significant independent relationship between MSNA burst frequency and VE/VCO(2) (P=0.013) that differed between HF and controls (P<0.01).

Conclusions: The magnitude of resting sympathetic activity correlates positively with the VE/VCO(2) slope. Augmentation of this relationship in HF patients is consistent with the concept that enhanced mechanoreceptor reflex activity exaggerates their ventilatory response to exercise.

Figure 1)

Regression equations (slope + intercept) describing the relationship between muscle sympathetic nerve activity (MSNA) and the slope of the ratio of ventilation to carbon dioxide output (VE/VCO₂) in heart failure patients (filled squares and solid trendline) (VE/VCO₂ = 0.20 × MSNA + 23.4; P=0.005, r=0.50) and controls (unfilled circles and dashed trendline) (VE/VCO₂ = 0.11 × MSNA + 22.2; P=0.046, r=0.36). *P=0.001 for difference between subjects with and without heart failure