Airflow Obstruction and Reversibility in Spinal Cord Injury: Evidence for Functional Sympathetic Innervation

doi:10.1016/j.apmr.2008.06.011

Archives of Physical Medicine and Rehabilitation

Volume 89, Issue 12, December 2008, Pages 2349-2353

https://doi.org/10.1016/j.apmr.2008.06.011 Get rights and content

Abstract

Radulovic M, Schilero GJ, Wecht JM, Weir JP, Spungen AM, Bauman WA, Lesser M. Airflow obstruction and reversibility in spinal cord injury: evidence for functional sympathetic innervation.

Objectives

The first objective was to assess group differences for specific airway conductance (sGaw) among subjects with tetraplegia, high paraplegia (HP: T2-T6), and low paraplegia (LP: T10-L4). The second objective was to determine the significance of responsiveness to ipratropium bromide (IB) by the assessment of the inherent variability of baseline measurements for impulse oscillation (IOS), body plethysmography, and spirometry.

Design

Prospective cross-sectional intervention study.

Setting

James J. Peters Veterans Administration Medical Center.

Participants

Subjects (N=43): 12 with tetraplegia (C4-8), 11 with HP, 11 with LP, and 9 controls.

Interventions

Not applicable.

Main Outcome Measures

Measurement of IOS, body plethysmography, and spirometry parameters at baseline and 30 minutes after IB.

Results

Baseline sGaw was significantly lower in tetraplegia (0.14±0.03) compared with HP (0.19±0.05) and LP (0.19±0.04) patients. By use of minimal difference to evaluate IB responsiveness in tetraplegia, 4 of 12 and 12 of 12 subjects had significant increases in forced expiratory volume in 1 second and sGaw, respectively, whereas 11 of 12 and 10 of 12 subjects had significant decreases in respiratory resistances measured at 5 and 20Hz (R5 and R20), respectively.

Conclusions

The finding of group differences for baseline sGaw supports the hypothesis that human lung contains functional sympathetic innervation. Body plethysmography and IOS were comparable in detecting IB-induced bronchodilation in tetraplegia and significantly more sensitive than spirometry.

Section snippets

Subjects

Forty-three subjects participated in the study. Thirty-four had chronic SCI of at least 6 months duration; 12 had tetraplegia (C4-7), 11 had HP (T2-6), and 11 had LP (T10-L4). The level and completeness of injury were determined by the 2003 Revised American Spinal Cord Injury Association classification.¹⁶ Nine able-bodied individuals served as controls. The number of individuals with HP at each specific thoracic level of injury was as follows: T2 equal to 1, T3 equal to 3, T4 equal to 5, T5

Results

Demographics and baseline pulmonary function parameters are shown (Table 1, Table 2). At baseline, sGaw was significantly lower and Raw was significantly higher in the group with tetraplegia compared with the other 3 groups. Among subjects with HP, baseline sGaw was low in the individual with a T2 injury (0.137) but comparable for the rest of the group (mean=0.195). Respiratory resistances at 5 and 20Hz (R5 and R20, respectively) were higher among subjects with tetraplegia and LP compared with

Discussion

The finding in the current study that baseline sGaw was significantly lower among subjects with tetraplegia compared with those with HP or LP, among whom sGaw values were comparable, supports the hypothesis that sympathetic innervation of human lung is more contributory to the modulation of airway tone than circulating epinephrine. Apparently even partial sympathetic innervation is functionally sufficient because most of the subjects with HP had lesions in the T3 to T4 region. Of note, the 1

Conclusions

The clinical significance of low baseline airway caliber and hyperresponsiveness to IB in tetraplegia is unknown. Although the majority of individuals report breathlessness,³⁵ it has not been determined if the increased work of breathing because of baseline airway obstruction contributes to this complaint or if the long-term administration of an anticholinergic agent would be efficacious in reducing respiratory symptoms.

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Circumstantially, high paraplegics and tetraplegics have similar levels of airway calibre as low paraplegics but higher epinephrine levels (Schmidt et al., 1998; Radulovic et al., 2008). Similarly, bronchial tone decreases in SCI patients following bilateral T2-3 sympathectomy (Radulovic et al., 2008). Recently we have discovered another potentially latent pathway which becomes active following acute spinal cord transection.
The maintenance of blood gas and pH homeostasis is essential to life. As such breathing, and the mechanisms which control ventilation, must be tightly regulated yet highly plastic and dynamic. However, injury to the spinal cord prevents the medullary areas which control respiration from connecting to respiratory effectors and feedback mechanisms below the level of the lesion. This trauma typically leads to severe and permanent functional deficits in the respiratory motor system. However, endogenous mechanisms of plasticity occur following spinal cord injury to facilitate respiration and help recover pulmonary ventilation. These mechanisms include the activation of spared or latent pathways, endogenous sprouting or synaptogenesis, and the possible formation of new respiratory control centres. Acting in combination, these processes provide a means to facilitate respiratory support following spinal cord trauma. However, they are by no means sufficient to return pulmonary function to pre-injury levels. A major challenge in the study of spinal cord injury is to understand and enhance the systems of endogenous plasticity which arise to facilitate respiration to mediate effective treatments for pulmonary dysfunction.
Drawing breath without the command of effectors: The control of respiration following spinal cord injury
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A more controversial pathway that is activated following SCI to mediate respiratory function is that of sympathetic innervation of bronchial smooth muscle (Partanen et al., 1982; Laitinen et al., 1985) which may act to facilitate airway tone. Circumstantially, high paraplegics and tetraplegics have similar levels of airway caliber as low paraplegics but higher epinephrine levels (Schmidt et al., 1998; Radulovic et al., 2008). Similarly, bronchial tone decreases in SCI patients following bilateral T2-3 sympathectomy (Radulovic et al., 2008).
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In regards to SCI and airway caliber, an important consideration is that injuries to the cord can create an “imbalance” between parasympathetic and sympathetic outflow. Thus, parasympathetic innervation of the lungs and airways is usually preserved after SCI, but sympathetic inputs can be profoundly disrupted (Radulovic et al., 2008). For example, autonomic dysreflexia following SCI is thought to result, at least in part, from impaired regulation of sympathetic motor outflow.
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: Supported by the Veterans Administration Rehabilitation Research and Development Center of Excellence (grant no. B4162C).

: No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.

: Reprints are not available from the authors.

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Original articleAirflow Obstruction and Reversibility in Spinal Cord Injury: Evidence for Functional Sympathetic Innervation

Abstract

Objectives

Design

Setting

Participants

Interventions

Main Outcome Measures

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Conclusions

J Auton Nerv Syst

Respir Physiol

J Auton Nerv Syst

Chest

Chest

Arch Phys Med Rehabil

Chest

J Clin Neurosci

J Thorac Cardiovasc Surg

Respir Physiol

Pulm Pharmacol Ther

Chest

Chest

Chest

Neuromuscular structure and function in the airways

Fed Proc

Catecholamine- and acetylcholinesterase-containing nerves in human lower respiratory tract

Histochemistry

Innervation of airway smooth muscle

Am Rev Respir Dis

Original article
Airflow Obstruction and Reversibility in Spinal Cord Injury: Evidence for Functional Sympathetic Innervation