Gill, Luther

Compensatory respiratory plasticity is critical to preserve breathing capacity after phrenic denervation (DNV), when the contribution of the ipsilateral phrenic motor neuron (PhrMn) pool is abolished and the force generating capacity of the diaphragm muscle (DIAm) is compromised. In rats, ventilation is maintained after DNV, and this is most likely mediated by an increase in central drive to the contralateral PhrMn pool. The extent of central drive to PhrMns was estimated by measuring the root mean square (RMS) of DIAm EMG at 75ms (RMS 75 ) after the onset of activity. Transdiaphragmatic pressure (Pdi) was measured to estimate DIAm force. We hypothesized that after unilateral DNV central drive to the contralateral PhrMn pool increases across motor behaviors. Immediately following DNV, there was a significant increase in RMS 75 during ventilatory behaviors (eupnea, and hypoxia‐hypercapnia). RMS 75 did not change during non‐ventilatory behaviors (airway occlusion). These results indicate that after DNV there is: 1) an increase in central drive to the contralateral PhrMn pool during ventilatory behaviors such that Pdi was maintained; 2) central drive to the contralateral PhrMn pool was unchanged during more forceful (greater than ~50% Pdi max ) non‐ventilatory behaviors, suggesting that central drive was near maximum. These results highlight the compensatory plasticity in the neural control of the DIAm and the importance of measuring multiple motor behaviors.

Ventilatory behaviors across a range of species including humans require less than 50% of maximal force‐generating capacity by the diaphragm muscle, the main inspiratory muscle in mammals. Near maximal forces are only generated during expulsive behaviors usually associated with airway clearance. There is ongoing controversy regarding the impact of unilateral lesions (e.g., spinal cord injury, denervation) on ventilatory outcomes. We hypothesized that unilateral denervation of the diaphragm muscle in rats and mice would minimally impact ventilation. Transdiaphragmatic pressure (Pdi) measurements were used to estimate diaphragm muscle force in adult male rats and mice. Following acute, unilateral phrenic nerve transection in the neck, there was no change in Pdi during eupnea or hypoxia‐hypercapnia in rats or mice. Reduced Pdi was evident during deep breaths and tracheal occlusion (behaviors associated with ~70% of maximal Pdi elicited by bilateral phrenic nerve stimulation) in both species. These results are also consistent with the lack of changes in tidal volume or respiratory pattern during eupnea measured by whole body plethysmography in unrestrained, spontaneously breathing rats after mid‐cervical contusion or hemisection injuries. These results highlight the large reserve capacity for force generation by the diaphragm muscle in rodents and the importance of measuring multiple motor behaviors. Grant Funding Source : Supported by HL096750, AG044615, HL105355 and Mayo Center for Regenerative Medicine