Respiratory sensations, cardiovascular control, kinaesthesia and transcranial stimulation during paralysis in humans.

Abstract

SUMMARY1. To determine whether discomfort associated with breathing (dyspnoea) is related to the chemical drive to breath, three subjects were totally paralysed while fully conscious. Subjective responses to a rising C02 stimulus were obtained during rebreathing, rebreathing with C02 added, and breath holding. Dyspnoea was measured with a 10-point Borg scale.2. Following nasotracheal intubation and ventilation (oxygen saturation, 02,Sat' 98-100°% and end-tidal C02, PET,CO,, 30-40 mmHg), total neuromuscular blockade was induced by a rapid injection of atracurium (>2'5 mg kg1) and complete paralysis was maintained with an infusion (5 mg (kg h)-'). Paralysis was confirmed by abolition of the compound muscle action potentials of both the diaphragm and abductor hallucis evoked by supramaximal electrical stimulation of the relevant nerves. Communication via finger movement was preserved for the first 20-30 min following paralysis by inflation of a sphygmomanometer cuff on one arm.3. Before and during complete paralysis, dyspnoea increased progressively during hypercapnia produced by rebreathing (with or without C02 added to the circuit at 250 ml min-'). The mean PET,CO, eliciting 'severe' dyspnoea was 46 mmHg during rebreathing, 42 mmHg during 'breath holding', and 52 mmHg during rebreathing with added C02. There were no significant differences between the values obtained during paralysis and in the control study immediately before paralysis. S. C. GANDEVIA AND OTHERS evokes, can lead to discomfort in the absence of any contraction of respiratory muscles. 5. During paralysis, attempted contraction of arm, leg and trunk muscles increased heart rate and blood pressure. For attempted handgrip contractions, the increases in heart rate (range, 7-15 beats min-') and mean arterial pressure (range, 20-32 mmHg) were similar to those recorded with actual contractions in trials immediately before paralysis. In one subject, graded increases in heart rate and blood pressure occurred for attempted contractions of 45 s duration over a range of intensities (0-100% maximal effort).6. During complete paralysis, transcranial electromagnetic stimulation of the motor cortex produced illusory twitch-like movements of the wrist and digits. This also occurred in separate studies during complete ischaemic paralysis and anaesthesia of the forearm and hand. These illusory movements thus reflect activation of intracerebral structures by the induced currents. No sensation of effort accompanied the transcranial stimuli delivered during whole-body paralysis.7. Attempted voluntary movement of a limb paralysed with intravenous atracurium was accompanied by a marked sense of effort, but it also produced definite illusions of movement. The limb appeared to move slowly in the opposite direction to that desired. However, in separate studies, these illusions were absent when all large diameter axons in the arm were blocked by ischaemia. This suggests that the illusory limb movements were due to incomplete neuromuscular block of the intrafusal endplates.

Motor-Unit Activity Differs With Load Type During a Fatiguing Contraction

“…Based on the associated adjustments, the increase in motor-unit activity likely involves an augmentation of both the descending drive and sensory feedback from the periphery. Regulation of MAP and heart rate during static contractions of moderate intensity, for example, can be achieved primarily by the motor command (Gandevia and Hobbs 1990;Gandevia et al 1993;Ogoh et al 2002), whereas activation of the group III and IV afferents during fatiguing contractions contributes to the reflex-mediated increase in the MAP (Alam and Smirk 1937;Kaufman et al 1988;Rowell 1993;Rowell and O'Leary 1990). Similarly, the rating of perceived exertion appears to involve an interaction between a corollary of the central motor command and peripheral afferent feedback (Carson et al 2002).…”

An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea

“…From the 1960s through the 1980s, it was widely believed that the sense of respiratory effort/work was responsible for all dyspnea (e.g., see Reference 45), an idea that has been disproved (46)(47)(48). Nonetheless, an uncomfortable sense of respiratory "work" and "effort" is commonly reported by patients with conditions such as asthma, chronic obstructive pulmonary disease (COPD), and diseases that impair respiratory muscle performance (27,31,32).…”

“…It has been reported in quadriplegic patients in response to increased partial pressure of carbon dioxide (PCO 2 ) (47), decreased tidal volume (100), or methacholine challenge (66), as well as in response to increased PCO 2 in normal subjects undergoing neuromuscular blockade (46,48). In addition, patients with asthma, COPD, interstitial lung disease, and idiopathic hyperventilation are significantly more likely than healthy control subjects to report perceptions of air hunger when recalling perceptions of breathing at the end of exercise (113).…”

Direct measurement of cardiac sympathetic efferent nerve activity during dynamic exercise

“…A period of Ͼ30 min was allowed to establish that the animal was quiescent and that the cardiovascular variables had become stable. To determine the changes in CSNA, HR, and mean AP (MAP) during treadmill exercise and the effects of exercise intensity on their responses, a series of exercise trials was performed in five cats for 1 min at 0°incline with different treadmill speeds (10,20,30,40,50, and 60 m/min). A rest for 10-30 min between trials of exercise was taken depending on the exercise intensity.…”

“…Heart rate (HR) and stroke volume are increased during rhythmic or dynamic exercise, which in turn produces an increase in cardiac output (8,25,27,44). HR, ventilatory rate, and arterial blood pressure (AP) are also increased during mental simulation of motor action without any actual contraction (5,45) and during attempted handgrip exercise under partial or total neuromuscular blockade (10,36), suggesting that the cardiac adaptation during exercise is a neurogenic response via the autonomic nervous system partly due to a signal descending from the higher central nervous system. When such autonomic regulation is lacking in heart transplant recipients or cardiac denervated dogs, the responses of HR and cardiac output to dynamic exercise are diminished and slowed down despite a compensatory rise in stroke volume (2,7,39).…”