Phrenic-to-intercostal reflex activity in response to high frequency spinal cord stimulation (HF-SCS)

Abstract

Objective: HF-SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic-to-intercostal reflex during HF-SCS.

Methods: In 5 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the left and right external intercostal muscles (EI) in the 3rd interspace before and after sequential left and right phrenicotomy.

Results: Mean control peak firing frequency of the right EI and left EI was 11.4 ± 0.3 Hz and 10.6 ± 0.3 Hz respectively. Following unilateral right phrenic nerve section, mean SMU peak firing frequency of right EI (ipsilateral to the section) was significantly greater when compared to control (15.9 ± 0.5 Hz vs 11.4 ± 0.3 Hz; p = 0.01). Mean SMU peak firing frequency of the contralateral left EI remained unchanged (10.2 ± 0.3 Hz vs 10.6 ± 0.3 Hz, p = 0.40). Subsequent, section of the left phrenic nerve resulted in significantly higher mean SMU peak firing frequency of the left EI (16.2 ± 0.5 Hz vs 10.2 ± 0.3 Hz) when compared to before section p = 0.01). Contralateral, right EI peak firing frequency was not different if compared to before left phrenic nerve section (16.9 ± 0.4 Hz vs. 15.9 ± 0.5 Hz; p = 0.14).

Conclusion: This study demonstrates that during HF-SCS: 1) unilateral diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral EI muscles, 2) the neural circuitry mediating the phrenic-to-intercostal reflex is preserved at a spinal level and does not require supraspinal input and 3) unilateral compensatory increases were observed in EI muscle activation following ipsilateral diaphragm paralysis.

Keywords: Diaphragm; Intercostal; Muscle; Phrenic; Reflex; Respiration.

Fig. 1.

Experimental set-up.

Fig. 2.

Multiunit EMGs of the external intercostal muscle during spontaneous breathing (left panel) and during HF-SCS (right panel) with stimulus parameters set to achieve comparable inspired volumes.

Fig. 3.

Single motor unit recordings from the external intercostal muscles during HF-SCS before and following right (A,C,E) and left (B,D,F) phrenic sections in a single animal. From top to bottom, tracings represent single motor unit EMG recordings of the EI from the ventral portion of the 3rd interspace. All the action potentials from each motor unit are superimposed on the right of each tracing. See text for further explanation.

Fig. 4.

Histograms of the peak frequencies of all single motor units identified in the 3rd interspace during HF-SCS before (black bars) and after (gray bars) phrenic nerve sections. Bin width: 1.0 Hz. Results from analysis of variance are presented below.