Muscle mechanoreceptor sensitivity in heart failure.
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.
Div. of Cardiology, 47-123 CHS, UCLA Dept. of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095, USA. hmiddlekauff@mednet.ucla.edu
Holly R
HR
Middlekauff
Josephine
J
Chiu
Michele A
MA
Hamilton
Gregg C
GC
Fonarow
W Robb
WR
Maclellan
Antoine
A
Hage
Jaime
J
Moriguchi
Jignash
J
Patel
D001132:Arm; D002303:Cardiac Output, Low / Q000503:physiopathology*; D003250:Constriction; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D018737:Hand Strength; D006801:Humans; D019344:Lactic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008465:Mechanoreceptors / Q000503:physiopathology*; D008875:Middle Aged; D009038:Motion; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation*; D010507:Periodicity; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D019344:Lactic Acid; D003999:Dichloroacetic Acid