Activation of inspiratory muscles via spinal cord stimulation

Abstract

Diaphragm pacing is a clinically useful modality providing artificial ventilatory support in patients with ventilator dependent spinal cord injury. Since this technique is successful in providing full-time ventilatory support in only ~50% of patients, better methods are needed. In this paper, we review a novel method of inspiratory muscle activation involving the application of electrical stimulation applied to the ventral surface of the upper thoracic spinal cord at high stimulus frequencies (300 Hz). In an animal model, high frequency spinal cord stimulation (HF-SCS) results in synchronous activation of both the diaphragm and inspiratory intercostal muscles. Since this method results in an asynchronous pattern of EMG activity and mean peak firing frequencies similar to those observed during spontaneous breathing, HF-SCS is a more physiologic form of inspiratory muscle activation. Further, ventilation can be maintained on a long-term basis with repetitive stimulation at low stimulus amplitudes (<1 mA). These preliminary results suggest that HF-SCS holds promise as a more successful method of inspiratory muscle pacing.

Keywords: Diaphragm pacing; Inspiratory muscles; Spinal cord injury; Spinal cord stimulation.

Figure 1

Relationships between stimulus amplitude and inspired volume (left panel) and negative airway pressure generation (right panel) at different stimulus frequencies. With increasing stimulus frequencies between 50 and 300, there were significant increases in the magnitude of these parameters. The 300 and 400 Hz curves, however, were not statistically different. With HF-SCS, large inspired volumes and airway pressures were generated with small stimulus amplitudes. Peak values were achieved with 2–3 mA.

Figure 2

Multiunit EMGs of the parasternal intercostal muscle, external intercostal muscle and diaphragm during spontaneous breathing (left panel) and during HF-SCS (right panel) at comparable inspired volumes. As with spontaneous breathing, HF-SCS results in an asynchronous EMG pattern of activation. This pattern is in marked contrast to the synchronous EMG pattern observed during phrenic nerve stimulation.

Figure 3

Examples of single motor unit recordings from the diaphragm during HF-SCS in one animal. Three separate motor units are readily identified. Each of the action potentials from the three SMUs is shown superimposed to the right, confirming their similar morphology. See text for further explanation.

Figure 4

SMU activity recorded from the parasternal intercostal muscle, external intercostal muscle and diaphragm during spontaneous breathing (left panel) and during HF-SCS (right panel) in one animal. EMG, instantaneous motor unit discharge frequency and the corresponding volume are plotted in each panel. All the action potentials from each SMU are superimposed on the right. Note that during both spontaneous breathing and HF-SCS, discharge frequencies of single motor units gradually increase during the first part of inspiration until a plateau is reached and then gradually decline. Note also that there were no significant differences in SMU firing frequencies between spontaneous breathing and HF-SCS.

Figure 5

Histograms of the discharge frequencies of all single motor units identified in the dorsal portion of the 3^rd interspace (upper panel), ventral portion of the 3^rd interspace (middle panel) and dorsal portion of the 5^th interspace (lower panel) during spontaneous breathing (grey bars) and during HF-SCS (dark bars). Bin width, 1 Hz. Recordings were obtained under conditions in which inspired volume during HF-SCS was matched to inspired volumes recorded during spontaneous breathing by adjustment of stimulus amplitude. Note that mean peak firing frequencies were significantly higher during HF-SCS compared to spontaneous breathing due to the higher absolute ribcage contribution to inspired volume. However, dorsoventral and rostrocaudal gradients of distribution of inspiratory drive observed during spontaneous activity were similar to those occurring during HF-SCS.

Figure 6

Negative airway pressure generation (Paw) (following airway occlusion), inspired volume, end-tidal PCO₂, oxygen saturation, mean blood pressure and heart rate are plotted every 30 min during continuous inspiratory muscle pacing with HF-SCS. Results are means ± SE. Airway pressure and inspired volume generation remained constant throughout the initial 5.5 hours of stimulation. End-tidal PCO₂ and oxygen saturation were also maintained between 35–40 mmHg and 95–99%, respectively. Mean blood pressure and heart rate also remained stable throughout this period. After 5.5 hour of continuous pacing, stimulus parameters were increased (indicated by arrows) resulting in an increase in inspired volume and consequent fall in PCO_2, which was sustained over a 30 min period. These results indicate that adequate levels of ventilation can be maintained over a prolonged period with HF-SCS.

Figure 7

Negative airway pressure generation (Paw) (following airway occlusion), inspired volume, end-tidal PCO₂, oxygen saturation, mean blood pressure and heart rate are plotted every 30 min during continuous inspiratory muscle pacing with HF-SCS after bilateral phrenicotomy. Results are means ± SE. Airway pressure and inspired volume generation remained constant throughout the initial 5.5 hours of stimulation. End-tidal PCO₂ and oxygen saturation were also maintained around 40 mmHg and 94%, respectively. Mean blood pressure and heart rate also remained stable throughout this period. After 5.5 hour of continuous pacing, stimulus parameters were increased (indicated by arrows) resulting in an increase in inspired volume and consequent fall in PCO_2, which was sustained over a 30 min period. These results indicate that adequate levels of ventilation can be maintained over a prolonged period with HF-SCS of the intercostal muscles alone.

Figure 8

A simplified diagram of potential spinal cord tracts mediating activation of the phrenic motoneuron pools during upper thoracic HF-SCS in the dog model. To mimic spinal cord injury and localized potential involvement of different groups of neurons, HF-SCS was performed under control conditions and following sequential section of the spinal cord: at the C1 and C4 (high tetraplegia with injury above the phrenic pool of motoneurons) and C8 (low tetraplegia with injury below the phrenic pool of motoneurons) spinal levels. The dotted horizontal lines indicate the areas of spinal cord section. See text for further explanation.

Figure 9

The effects of sequential section of the spinal cord at the C4 and C8 spinal levels on parasternal intercostal and diaphragm EMG activation and inspired volume generation during HF-SCS (2 mA, 300 Hz, 0.2ms pulse width) in a representative animal. Following sequential section at the C4 level and dorsal columns at the C8 level, there were no significant changes in peak integrated diaphragm EMG activity or inspired volume compared to control values. However, following section of the lateral funiculi at the C8 level, there was a marked reduction in the degree of diaphragm activation and associated marked reduction in inspired volume generation. There were no further changes following complete section. In contrast, there were no changes in peak integrated parasternal EMG following all spinal sections. See text for further explanation.

Figure 10

Mean inspired volume during HF-SCS at different levels of stimulation under control conditions and following sequential section of the spinal cord. Note that following sequential section at the C4 level and dorsal columns at the C8 level, there were no significant changes in mean inspired volume compared to control values. However, section of the lateral funiculi at the C8 level resulted in a marked reduction in mean inspired volume generation. There were no further changes following complete section. See text for further explanation.

Figure 11

Mean airway pressure generation during HF-SCS at different levels of stimulation under control conditions and following sequential section of the spinal cord. Note that following sequential section at the C4 level and dorsal columns at the C8 level, there were no signficant changes in mean airway pressure generation compared to control values. However, section of the lateral funiculi at the C8 level resulted in a marked reduction in mean airway pressure generation. There were no further changes following complete section. See text for further explanation.