Effect of phrenic afferent stimulation on pattern of respiratory muscle activation.

Ventilation and electromyogram (EMG) activities of the right hemidiaphragm, parasternal intercostal, triangularis sterni, transversus abdominis, genioglossus, and alae nasi muscles were measured before and during central stimulation of the left thoracic phrenic nerve in 10 alpha-chloralose anesthetized vagotomized dogs. Pressure in the carotid sinuses was fixed to maintain baroreflex activity constant. The nerve was stimulated for 1 min with a frequency of 40 Hz and stimulus duration of 1 ms at voltages of 5, 10, 20, and 30 times twitch threshold (TT). At five times TT, no change in ventilation or EMG activity occurred. At 10 times TT, neither tidal volume nor breathing frequency increased sufficiently to reach statistical significance, although the change in their product (minute ventilation) was significant (P less than 0.05). At 20 and 30 times TT, increases in both breathing frequency and tidal volume were significant. At these stimulus intensities, the increases in ventilation were accompanied by approximately equal increases in the activity of the diaphragm, parasternal, and alae nasi muscles. The increase in genioglossus activity was much greater than that of the other inspiratory muscles. Phrenic nerve stimulation also elicited inhomogeneous activation of the expiratory muscles. The transversus abdominis activity increased significantly at intensities from 10 to 30 times TT, whereas the activity of the triangularis sterni remained unchanged. The high stimulation intensities required suggest that the activation of afferent fiber groups III and IV is involved in the response. We conclude that thin-fiber phrenic afferent activation exerts a nonuniform effect on the upper airway, rib cage, and abdominal muscles and may play a role in the control of respiratory muscle recruitment.     

Respiratory sensation and pattern of respiratory muscle activation during diaphragm fatigue

We have examined the relationship between respiratory effort sensation (modified Borg scale) and amplitude of the integrated surface electromyogram of the diaphragm (Edi, esophageal electrode), rib cage muscles (Erc), and sternomastoid muscle (Esm) during the development of diaphragm fatigue in five normal subjects. Three conditions were studied: run A: transdiaphragmatic pressure (Pdi), 65% Pdimax; esophageal pressure (Pes), 60% Pesmax; run B: Pdi, 50% Pdimax; Pes, 60% Pesmax; and run C: Pdi, 50% Pdimax; Pes, 20% Pesmax. During all runs there was a progressive rise in sensation, which was greater in runs A and B than in run C (P less than 0.05, analysis of variance). There was no difference between runs A and B. At the end of run C subjects did not report a maximal Borg score despite their inability to generate the target Pdi. The increase in sensory score with fatigue correlated highly with Esm/Esmmax and with Erc/Ercmax. There was no correlation between sensory score and Edi/Edimax. We conclude that the increase in respiratory effort sensation that accompanies diaphragm fatigue is not due to perception of increased diaphragmatic activation. It may reflect increased overall respiratory motor output not directed to the diaphragm.     

Effect of hypercapnia and hypoxia on respiratory muscle activation in humans

We studied the electromyographic activity of the diaphragm (EMGdi) and abdominal external oblique (EMGeo) muscles in response to progressive hypercapnia (HCVR) and hypoxia (HVR) in five normal males. The slopes of the regression lines relating log EMGdi activity to minute volume of ventilation (VE) were steeper during HVR runs than HCVR runs (mean +/- SE, 0.03201 +/- 0.00724 vs. 0.02729 +/- 0.00676, P less than 0.03). Phasic expiratory EMGeo activity was seen in 15 of 15 HCVR runs but in only 6 of 15 HVR runs. Furthermore, the maximum level of VE attained before the onset of EMGeo activity was significantly lower during HCVR runs than during HVR runs (23.1 +/- 2.5 vs. 34.8 +/- 4.01/min, P less than 0.003). We conclude that in awake humans 1) the diaphragm is activated to a greater extent by hypoxia than hypercapnia at a given VE and 2) hypercapnia causes a more consistent recruitment of abdominal expiratory activity at lower VE than does hypoxia.     

Synchronization of respiratory frequency by somatic afferent stimulation.

In cats anesthetized with chloralose-urethan, vagotomized, paralyzed, and artifically ventilated, superficial radial (cutaneous) and hamstring (muscle) nerve afferents were stimulated while phrenic nerve electrical activity was recorded. The results obtained with both types of nerves were similar. Stimulation in mid and late expiration advanced the onset of the next inspiration, shortening its duration. Stimulation in early inspiration advanced, while that in late inspiration delayed, the onset of the next expiration. These effects were often accompanied by changes in phrenic motoneuron firing patterns (earlier recruitment, increased discharge frequency, increased slope of integrated phrenic neurogram). Repetitive somatic afferent stimulation produced sustained increases in respiratory frequency in all cats and in half of them entrainment of respiratory frequency to the frequency of stimulation occurred at ratios such as 4:3, 4:5, 1:2, 1:3, 1:4, and 1:7. The lowest stimulus intensity required for evoking these phase shifts was between 5 and 10T (threshold of most excitable fibers) for muscle afferents and between 1 and 2T for cutaneous afferents. These results demonstrate the existence of a reflex mechanism capable of locking respiratory frequency to that of a periodic somatic afferent input. They also provide an experimental basis for the hypothesis that reflexes are resposible for the observed locking between step or pedal frequency and respiratory rate during exercise in man.     

Effect of resistive loads on pattern of respiratory muscle recruitment during exercise.

In healthy subjects, we compared the effects of an expiratory (ERL) and an inspiratory (IRL) resistive load (6 cmH2O.l-1.s) with no added resistive load on the pattern of respiratory muscle recruitment during exercise. Fifteen male subjects performed three exercise tests at 40% of maximum O2 uptake: 1) with no-added-resistive load (control), 2) with ERL, and 3) with IRL. In all subjects, we measured breathing pattern and mouth occlusion pressure (P0.1) from the 3rd min of exercise, in 10 subjects O2 uptake (VO2), CO2 output (VCO2), and respiratory exchange ratio (R), and in 5 subjects we measured gastric (Pga), pleural (Ppl), and transdiaphragmatic (Pdi) pressures. Both ERL and IRL induced a high increase of P0.1 and a decrease of minute ventilation. ERL induced a prolongation of expiratory time with a reduction of inspiratory time (TI), mean expiratory flow, and ratio of inspiratory to total time of the respiratory cycle (TI/TT). IRL induced a prolongation of TI with a decrease of mean inspiratory flow and an increase of tidal volume and TI/TT. With ERL, in two subjects, Pga increased and Ppl decreased more during inspiration than during control suggesting that the diaphragm was the most active muscle. In one subject, the increases of Ppl and Pga were weak; thus Pdi increased very little. In the two other subjects, Ppl decreased more during inspiration but Pga also decreased, leading to a decrease of Pdi. This suggests a recruitment of abdominal muscles during expiration and of accessory and intercostal muscles during inspiration. With IRL, in all subjects, Ppl again decreased more, Pga began to decrease until 40% of TI and then increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of adequate stimulation on the discharge pattern of an isolated frog muscle spindle

Discharges from an isolated frog muscle spindle during mechanical stimulation of varied amplitude, velocity, and shape were investigated. The firing rate during a linear increase in strength of the stimulus is determined by its amplitude, whereas the change in firing rate is determined by the rate of increase of amplitude. With sinusoidal stimulation the firing rate apparently reproduces stimulus shape, i.e., the muscle spindle is sensitive not only to amplitude and velocity, but also to acceleration of the stimulus. Sensitivity to acceleration is most probably due to the change in threshold of appearance of action potentials observed during variation of the speed of stretching.P. K. Anokhin Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 426–433, July–August, 1976.     

Effect of diaphragm small-fiber afferent stimulation on ventilation in dogs

Little is known regarding the role of diaphragm small-fiber afferents (groups III and IV) in the control of breathing. This study was designed to determine whether activation of these afferents with use of capsaicin affects phrenic efferent activity. Capsaicin injections into the phrenic artery were made in 10 alpha-chloralose-anesthetized dogs after each of the following procedures performed in succession: bilateral cervical vagotomy, C7 spinal cord transection, bilateral cervical dorsal rhizotomy. In six of these animals injections were also made after C2 spinal cord transection and removal of the cervical spinal cord. Injections made in the vagotomized animals were associated with apneusis followed by hyperpnea. C7 spinal transection eliminated the hyperpneic response, but the apneusis remained. Cervical dorsal rhizotomy or C2 spinal cord transection failed to abolish the apneusis in response to injection. No diaphragm response was obtained after removal of the cervical spinal cord. Experiments in three additional animals showed that capsaicin does not have a direct excitatory effect on the muscle cells of the crural diaphragm, nor does it potentiate the release of neurotransmitter in the diaphragm. The results of this study indicate that small-fiber afferents in the diaphragm have an excitatory effect on phrenic motoneurons. There is a segmental component to this reflex, since the response is observed after C2 spinal cord transection. The data also suggest that at least some of these afferents enter the spinal cord through the ventral roots.     

Effect of muscle storage and stimulation on the intensity of Z-reflection of its equatorial x-ray pattern

The maintenance of frog sartorius muscle in Ringer solution over a long period of time (24 h or more) increases Z-reflection intensity of equatorial X-ray pattern relative to that from fresh (1-2 h) dissecting muscle at sarcomere length more than 2.3 m. Long stimulation deteriorates the equatorial X-ray pattern from muscle. Then with the course of time Z-reflection intensity increases several times, Z and reflections merge, and rigor equatorial X-ray pattern is registered.     

Effect of activation by calcium on the x-ray diffraction pattern from insect flight muscle.

A low-angle X-ray diffraction pattern of calcium-activated Lethocerus flight muscle was formed and the intensities of various parts of the pattern observed by means of a proportional counter. The muscle was sinusoidally oscillated in length to produce mechanical work. The resultant changes in diffraction intensity were related to the state of the muscle and to the phase of the mechanical oscillatory cycle. The measurements were interpreted in terms of a movement of the heads of the myosin molecules into contact with the actin filaments. In these terms the results showed that between 10 and 20% of the myosin heads attached to actin during work-producing oscillation of the muscle. The time-course of this attachment followed that of tension generation with a small delay. Calculation suggests that not all of the myosin molecules attached to actin at any one moment were generating tension.     

Integration-differentiation and gating of carotid afferent traffic that shapes the respiratory pattern.

The phase-dependent plasticity of carotid chemoafferent signaling was studied with electrical stimulation of a carotid sinus nerve during either inspiration or expiration in anesthetized, glomectomized, vagotomized, paralyzed, and ventilated rats. Stroboscopic and interferometric analyses of the resulting phase-contrast disturbances of the respiratory rhythm revealed that carotid chemoafferent traffic was dynamically filtered centrally by a parallel bank of leaky integrators and differentiators, each being logically gated to the inspiratory or expiratory phase in a stop-and-go manner as follows: 1) carotid short-term potentiation of inspiratory drive was mediated by dual integrators that both shortened inspiration and augmented phrenic motor output cooperatively in long and short timescales; 2) carotid short-term depression of respiratory frequency was mediated by a (possibly pontine) integrator that lengthened expiration with a relatively long memory; and 3) carotid "chemoreflex" shortening of expiration was mediated by an occult fast integrator, which, together with carotid short-term depression, formed a differentiator. These effects were modulated anteriorly by integrators in the nucleus tractus solitarius that were "auto-gated" to, or recruited by, the carotid sinus nerve input. Such phase-selective and activity-dependent time-frequency filtering of carotid chemoafferent feedback in parallel neurological-neurodynamic central pathways may profoundly affect respiratory stability during hypoxia and sleep and could contribute to the dynamic optimization of the respiratory pattern and maintenance of homeostasis in health and in disease states.     

Effects of activation pattern on nonisometric human skeletal muscle performance.

During volitional muscle activation, motor units often fire with varying discharge patterns that include brief, high-frequency bursts of activity. These variations in the activation rate allow the central nervous system to precisely control the forces produced by the muscle. The present study explores how varying the instantaneous frequency of stimulation pulses within a train affects nonisometric muscle performance. The peak excursion produced in response to each stimulation train was considered as the primary measure of muscle performance. The results showed that at each frequency tested between 10 and 50 Hz, variable-frequency trains that took advantage of the catchlike property of skeletal muscle produced greater excursions than constant-frequency trains. In addition, variable-frequency trains that could achieve targeted trajectories with fewer pulses than constant-frequency trains were identified. These findings suggest that similar to voluntary muscle activation patterns, varying the instantaneous frequency within a train of pulses can be used to improve muscle performance during functional electrical stimulation.     

Effect of inspiratory muscle fatigue on breathing pattern

Our aim was to determine whether inspiratory muscle fatigue changes breathing pattern and whether any changes seen occur before mechanical fatigue develops. Nine normal subjects breathed through a variable inspiratory resistance with a predetermined mouth pressure (Pm) during inspiration and a fixed ratio of inspiratory time to total breath duration. Breathing pattern after resistive breathing (recovery breathing pattern) was compared with breathing pattern at rest and during CO2 rebreathing (control breathing pattern) for each subject. Relative rapid shallow breathing was seen after mechanical fatigue and also in experiments with electromyogram evidence of diaphragmatic fatigue where Pm was maintained at the predetermined level during the period of resistive breathing. In contrast there was no significant difference between recovery and control breathing patterns when neither mechanical nor electromyogram fatigue was seen. It is suggested that breathing pattern after inspiratory muscle fatigue changes in order to minimize respiratory sensation.     

Temperature modulates P2X receptor-mediated cardiovascular responses to muscle afferent activation

Static muscle contraction increases ATP release into the muscle interstitial space. Elevated ATP in muscle stimulates thin fiber muscle afferents and increases blood pressure via engagement of purinergic P2X receptors. In addition, ATP activates P2X receptors and enhances cardiovascular responses induced by stimulation of muscle mechanoreceptors. In this study, we examined whether elevated muscle temperature would attenuate and whether reduced temperature would potentiate P2X effects on reflex muscle responses. alpha,beta-Methylene ATP (alpha,beta-MeATP) was injected into the arterial blood supply of hindlimb muscle to stimulate P2X receptors, and muscle stretch was induced to activate mechanically sensitive muscle afferents as alpha,beta-MeATP was injected in 10 anesthetized cats. Femoral arterial injection of alpha,beta-MeATP (1.0 mM) increased mean arterial pressure (MAP) by 35+/-5 (35 degrees C), 26+/-3 (37 degrees C), and 19+/-3 mmHg (39 degrees C; P<0.05 vs. 35 degrees C), respectively. Muscle stretch (2 kg) elevated MAP. The MAP response was significantly enhanced 34% and 36% when alpha,beta-MeATP (0.2 mM) was arterially infused 5 min before muscle stretch at 35 degrees and 37 degrees C, respectively. However, as muscle temperature reached 39 degrees C, the stretch-evoked response was augmented only 6% by alpha,beta-MeATP injection, and the response was significantly attenuated compared with the response with muscle temperature of 35 degrees and 37 degrees C. In addition, we also examined effects of muscle temperature on alpha,beta-MeATP enhancement of the cardiovascular responses to static muscle contraction while the muscles were freely perfused and the circulation to the muscles was occluded. Because muscle temperature was 37 degrees C, arterial injections of alpha,beta-MeATP significantly augmented contraction-evoked MAP response by 49% (freely perfused) and 53% (ischemic condition), respectively. It is noted that this effect was significantly attenuated at a muscle temperature of 39 degrees C. These data indicate that the effect of P2X receptor on reflex muscle response is sensitive to alternations of muscle temperature and that elevated temperature attenuates the response.