Patients with spinal cord injury frequently suffer from respiratory complications due to their inability to cough and clear secretions. In recent animal studies, we have demonstrated that lower thoracic spinal cord stimulation (SCS) results in the generation of large increases in airway pressure and high peak flow rates. This technique, therefore, has the potential to produce an effective cough mechanism in spinal cord injured patients. Prior to clinical trials, however, there are important aspects of this technique that require further characterization. The following objectives are designed to assess the biology of this technique by examining the efficacy of SCS, identifying the specific muscles activated, evaluating the mechanism of their activation, and determining if SCS can prevent the development of expiratory muscle atrophy. In Objective I, the efficacy of SCS in terms of pressure generation will be e valuated by comparing this technique with other methods of expiratory muscle activation. First, SCS will be compared to a less invasive method of activating the expiratory muscles, i.e. surface stimulation of the abdominal wall. Second, we will test our hypothesis that SCS results in near maximal expiratory muscle activation by comparing SCS with direct stimulation of th ventral roots innervating the expiratory muscles. In Objective II, we plan to assess the pattern of muscle recruitment during SCS. Electromyographic techniques will be employed to evaluate the degree of electrical activation of various respiratory muscles located over a broad area of the chest wall. In addition, ablation techniques will be used to quantitate the mechanical contribution of these muscle groups to pressure generation. This data will allow us to assess the functional contribution of different muscle groups during lower thoracic SCS. In Objective III, the mechanism by which the motor nerves innervating the expiratory muscles are activated by lower thoracic SCS will be determined. We plan to assess the pathway(s) by which the ventral roots are stimulated and determine if synapses within the spina cord are involved. In separate trials, the electric field generated by current applied at over the lower thoracic cord will be determined. It is anticipated that this data may provide information leading to further refinement of this technique. In Objective IV, we will characterize the changes in expiratory muscle structure and function, following upper motoneuron denervation. An effective cough is dependent upon optimal function of the expiratory muscles and these muscles are most likely atrophied in patients with spinal cord injury. Therefore, we will also assess the capacity of electrical stimulation to maintain expiratory muscle function in a chronic animal model of spinal cord injury. The results of these studies should resolve important basic science issues concerning this technique in animals, and provide the framework for human clinical trials. Restoration of an effective cough mechanism may allow patients with spinal cord injury to clear secretions more easily, reduce the incidence of respiratory complications such as atelectasis and pneumonia and, ultimately, improve their life quality.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034143-12
Application #
2685316
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1986-02-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
2000-03-31
Support Year
12
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Romaniuk, Jaroslaw R; Dick, Thomas E; Bruce, Eugene N et al. (2017) Bifurcation of the respiratory response to lung inflation in anesthetized dogs. Respir Physiol Neurobiol 244:26-31
DiMarco, Anthony F; Kowalski, Krzysztof E (2008) Effects of chronic electrical stimulation on paralyzed expiratory muscles. J Appl Physiol 104:1634-40
Romaniuk, Jaroslaw R; Dick, Thomas E; Kowalski, Krzysztof E et al. (2007) Effects of pulse lung inflation on chest wall expiratory motor activity. J Appl Physiol 102:485-91
DiMarco, Anthony F; Kowalski, Krzysztof E; Romaniuk, Jaroslaw R (2007) Effects of diaphragm activation on airway pressure generation during lower thoracic spinal cord stimulation. Respir Physiol Neurobiol 159:102-7
Kowalski, Krzysztof E; Romaniuk, Jaroslaw R; DiMarco, Anthony F (2007) Changes in expiratory muscle function following spinal cord section. J Appl Physiol 102:1422-8
DiMarco, Anthony F; Takaoka, Yoshiro; Kowalski, Krzysztof E (2005) Combined intercostal and diaphragm pacing to provide artificial ventilation in patients with tetraplegia. Arch Phys Med Rehabil 86:1200-7
DiMarco, A F; Connors Jr, A F; Kowalski, K E (2004) Gas exchange during separate diaphragm and intercostal muscle breathing. J Appl Physiol 96:2120-4
DiMarco, A F; Kowalski, K E; Supinski, G et al. (2002) Mechanism of expiratory muscle activation during lower thoracic spinal cord stimulation. J Appl Physiol 92:2341-6
DiMarco, A F; Romaniuk, J R; Supinski, G et al. (2000) Effects of lung volume on parasternal pressure-generating capacity in dogs. Exp Physiol 85:331-7
DiMarco, A F; Romaniuk, J R; Kowalski, K E et al. (1999) Pattern of expiratory muscle activation during lower thoracic spinal cord stimulation. J Appl Physiol 86:1881-9

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