Muscle mechanoreceptor sensitivity in heart failure

Abstract

Prior work in animals suggests that muscle mechanoreceptor control of sympathetic activation (MSNA) during exercise in heart failure (HF) is heightened and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether 1) muscle mechanoreceptor control of MSNA is enhanced in HF patients and 2) lactic acid sensitizes muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in healthy humans and patients with HF. Dichloroacetate (DCA), which reduces the production of lactic acid, or saline control was infused in 12 patients with HF and 13 controls during RHG. MSNA was recorded (microneurography). After saline was administered and during exercise thereafter, MSNA increased earlier in HF compared with controls, consistent with baseline-heightened mechanoreceptor sensitivity. In both HF and controls, MSNA increased during the 3-min exercise protocol, consistent with further sensitization of muscle mechanoreceptors by metabolic by-product(s). During posthandgrip circulatory arrest, MSNA returned rapidly to baseline levels, excluding the muscle metaboreceptors as mediators of the sympathetic excitation during RHG. To isolate muscle mechanoreceptors from central command, we utilized passive exercise in 8 HF and 11 controls, and MSNA was recorded. MSNA increased significantly during passive exercise in HF but not in controls. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in healthy humans, and this muscle mechanoreceptor control is augmented further in HF. Neither lactate generation nor the fall in pH during RHG plays a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli resulting in exaggerated early increases in MSNA.

Sympathetic responses to exercise in myocardial infarction rats: a role of central command

“…However, it must be noted that contradicting data, regarding impairment of the sensitivity, have also been reported for the skeletal muscle vasculature (52). The amount of sympathetic activation has been reported to be excessive at rest and during exercise in CHF patients (24,29,36,42,47). Moreover, the excessive sympathetic activation in exercise has been suggested to be partially due to muscle mechanoreflex sensitization (26,27,29,30,34,44,45).…”

“…Specifically, sympathetic tone to muscle is elevated (24,29,36,42), renal vasoconstriction is enhanced (13,30,31,34), and the rise in muscle blood flow is attenuated in heart failure (13,25,35,41). The reduced blood supply to the kidney leads to excessive stimulation of renin secretion and inappropriate salt and water retention (6, 13), whereas the reduced skeletal muscle blood flow is an important contributor to exercise intolerance (51) in these patients.…”

“…It was reported that isolated activation of muscle metaboreflex by postexercise circulatory occlusion of the exercising limb resulted in less elevation of muscle SNA (36,47) and less renal vasoconstriction (30,31) in CHF patients than in healthy subjects, whereas the muscle mechanoreflex activation due to passive stretch or involuntary contraction of skeletal muscles evoked greater elevation of muscle SNA (29) and greater renal vasoconstriction (30,34) in CHF patients. Recent studies that used a decerebrated rat model have also shown muscle metaboreflex desensitization (26,46) and muscle mechanoreflex sensitization (26,44,45) in myocardial infarction (MI) animals.…”

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

“…HF patients with the lowest pVO2 exhibit the highest reflex sympathoneural responses to these stimuli (13). Similarly, if passive exercise is used to stimulate the afferent nerve endings that are responsive to stretch (mechanoreceptors, primarily type III fibres [14]) and remove the confounding influence of central command, MSNA increases reflexively in HF patients, but not in control subjects (15). Augmentation of these exercise pressor reflexes in HF could act as a peripheral neurogenic constraint to exercise in this condition.…”

Exercise pressor reflex in health and diseases: Animal studies

“…These observations suggest that the muscle metaboreflex is attenuated in HF. By contrast, the muscle mechanoreflex activation due to passive stretch of skeletal muscles evoked a significant elevation of muscle SNA 67) and enhanced renal vasoconstriction 68) in HF patients. These findings suggest that the muscle mechanoreflex is enhanced in HF.…”