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) and magnetic stimulation (MS) results in the generation of large increases in airway pressure and high peak flow rates. These techniques, therefore, have the potential to produce an effective cough mechanism in spinal cord injured patients. The purpose of these studies is to resolve important basic science issues concerning these techniques in animal studies. In OBJECTIVE I, the efficacy of cough by these techniques will be assessed by radiolabeled clearance studies. In OBJECTIVE II, the pathway(s) by which the motor nerves innervating the expiratory muscles are activated during SCS and MS will be determined. The importance of motor root activation via stimulation of spinal cord pathways will be assessed by monitoring pressure generation before and after sequential section of the ventral roots. The specific pathways responsible for pressure generation will be localized anatomically by evaluating the effects of spinal cord section. Nerve compound action potentials will also be recorded from the motor roots during stimulation. In OBJECTIVE III, the electric field generated around and within the spinal cord during SCS and MS will be measured and used in conjunction with finite element analysis modeling techniques to determine optimum electrode and coil design. 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 which are most likely atrophied in patients with spinal cord injury. Therefore, we will also assess the capacity or SCS and MS to maintain expiratory muscle function in a chronic animal model of spinal cord injury. In OBJECTIVE V, the safety profile of SCS will be assessed in chronic animals. The results of these studies should provide important information relevant to the potential use of these techniques in human clinical trials. Restoration of affective cough mechanism may allow patients with spinal cord injury to clear secretions more easily, reduce the incidence of respiratory complication 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 #
5R01HL034143-16
Application #
6637269
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Twery, Michael
Project Start
1986-02-01
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2005-07-31
Support Year
16
Fiscal Year
2003
Total Cost
$340,875
Indirect Cost
Name
Case Western Reserve University
Department
Physiology
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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