The sites of fatigue of human respiratory muscles have been compared with those observed in various limb muscles of different function and fiber type composition. Fatigue of the diaphragm was induced in normal subjects by either: a) breathing against an inspiratory resistance; or b) performing expulsive abdominal maneuvers, which minimize the use of intercostal and accessory muscles. With both protocols, the subjects were required to generate square-wave increases in transdiaphragmatic pressure (Pdi) of the required value (%Pdi max) using a 0.6 duty cycle at 12 breaths/min until the target Pdi could no longer be reached (Tlim). In most cases, diaphragm shortening was minimized by abdominal binding, so that the contractions were quasi-isometric. Similar patterns of intermittent, submaximal limb muscle contractions were performed at comparable relative forces (%MVC). For each muscle type, the responses to muscle stimulation interposed between voluntary contractions were measured for changes in muscle contractile strength; those superimposed on the target force, for changes in the relative degree of voluntary CNS activation. The evoked muscle M-waves were monitored for potential impairment of neuromuscular transmission. For stimulation of the diaphragm, supramaximal shocks were delivered bilaterally to the phrenic nerves. The results for limb muscles show that the loss of force during fatigue can be accounted for by peripheral contractile failure, and that the CNS can still cause full muscle activation. For the diaphragm, similar maximal CNS muscle activation was demonstrated prior to fatigue, but could not be achieved thereafter (superimposed twitches were still elicited during maximal efforts, and the estimated muscle strength always exceeded that which could be generated voluntarily). No evidence was seen for failure of transmission in either system. Thus, CNS inhibition appears to be an important factor in fatigue of respiratory muscles. We have shown that during fatigue of limb muscles, loss of force is accompanied by a decline in the maximum motor neuron firing frequency as the muscle contractile speed becomes slower. Since this slowing reduces the tetanic fusion frequency, the decline in discharge rates does not limit CNS muscle activation. The parallel between the changes in contractile speed and motor neuron firing rates suggests a regulating mechanism. We propose to explore whether this regulation resides within the CNS, or is due to a reflex from the fatigued muscle.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL030026-04
Application #
3341037
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1982-09-30
Project End
1990-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
John B. Pierce Laboratory, Inc.
Department
Type
DUNS #
City
New Haven
State
CT
Country
United States
Zip Code
06519
Thomas, C K; Johansson, R S; Bigland-Ritchie, B (2006) EMG changes in human thenar motor units with force potentiation and fatigue. J Neurophysiol 95:1518-26
Breugelmans, J G; Bazzy, A R (1997) Developmental differences in endplate response to P-type calcium channel blockade in the rat diaphragm. Brain Res Dev Brain Res 101:277-81
Bigland-Ritchie, B; Rice, C L; Garland, S J et al. (1995) Task-dependent factors in fatigue of human voluntary contractions. Adv Exp Med Biol 384:361-80
McKenzie, D K; Bigland-Ritchie, B; Gorman, R B et al. (1992) Central and peripheral fatigue of human diaphragm and limb muscles assessed by twitch interpolation. J Physiol 454:643-56
Thomas, C K; Bigland-Richie, B; Johansson, R S (1991) Force-frequency relationships of human thenar motor units. J Neurophysiol 65:1509-16
Thomas, C K; Johansson, R S; Bigland-Ritchie, B (1991) Attempts to physiologically classify human thenar motor units. J Neurophysiol 65:1501-8
Thomas, C K; Bigland-Ritchie, B; Westling, G et al. (1990) A comparison of human thenar motor-unit properties studied by intraneural motor-axon stimulation and spike-triggered averaging. J Neurophysiol 64:1347-51
Westling, G; Johansson, R S; Thomas, C K et al. (1990) Measurement of contractile and electrical properties of single human thenar motor units in response to intraneural motor-axon stimulation. J Neurophysiol 64:1331-8
Thomas, C K; Johansson, R S; Westling, G et al. (1990) Twitch properties of human thenar motor units measured in response to intraneural motor-axon stimulation. J Neurophysiol 64:1339-46
Woods, J J; Furbush, F; Bigland-Ritchie, B (1987) Evidence for a fatigue-induced reflex inhibition of motoneuron firing rates. J Neurophysiol 58:125-37

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