Increased mechanoreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure.

The concept that exercise limitation in patients with chronic heart failure (HF) is due to elevated filling pressures or inadequate cardiac output has been largely abandoned and replaced by a new paradigm. “The Muscle Hypothesis of HF,” originated by Drs. Coats and Piepoli, hypothesizes that abnormalities of skeletal muscle, including the sensory nerve fibers that mediate reflex changes in the circulation during exercise underlie the exercise limitations in HF (1, 11). The question debated today is which sensory fibers are responsible for the reflex abnormalities during exercise? Located within skeletal muscle, the sensory nerves mediating the reflex changes during exercise, termed the “Exercise Pressor Reflex,” consist of type III mechanoreceptor fibers that are principally sensitive to mechanical stimuli, and type IV metaboreceptor fibers that are principally sensitive to ischemic metabolites generated during exercise (3). In healthy humans, it is generally agreed that the muscle metaboreceptors, in conjunction with a contribution from the central nervous system (“Central Command”), mediate the increase in EPR. The notion that muscle mechanoreceptor sensitivity is augmented in HF was launched following the report that the muscle metaboreceptor contribution to EPR is blunted in HF (18). In humans, the muscle metaboreceptor contribution to reflex responses during exercise is isolated by “post-exercise circulatory arrest (PECA),” in which a blood pressure (BP) cuff proximal to the exercising muscle is inflated to suprasystolic levels at the termination of exercise. This traps ischemic metabolites within muscle and selectively engages metaboreceptors without 3 stimulating mechanoreceptors or central command. During 2 minutes of moderate handgrip exercise in NYHA Class II-IV HF patients, muscle sympathetic nerve activity (MSNA) increased, but then during PECA, which isolated the muscle metaboreceptors, plummeted to baseline levels ((18); Figure). Thus the metaboreflex is blunted in HF, and replaced by another system, such as muscle mechanoreflex or central command. If the muscle mechanoreflex were the mediator of the EPR in patients with HF, we would anticipate an immediate increase in MSNA at the onset of exercise, which would return to baseline during PECA. Low-level rhythmic exercise preferentially stimulates muscle mechanoreceptors over metaboreceptors. During low-level rhythmic handgrip (5), MSNA increased within the first minute of exercise in HF patients, but only in the third minute of exercise in healthy humans, consistent with heightened muscle mechanoreceptor sensitivity in HF. To further isolate the muscle mechanoreceptors from central command, passive exercise was employed and MSNA was recorded (5). MSNA increased significantly during passive exercise in HF patients, but not in healthy Page 1 of 14 Articles in PresS. J Appl Physiol (September 21, 2006). doi:10.1152/japplphysiol.00994.2006