Jaroslaw R. Romaniuk

Interaction between central pattern generators for breathing and swallowing in the cat.

1. We examined the interaction between central pattern generators for respiration and deglutition in decerebrate, vagotomized, paralysed and ventilated cats (n = 10), by recording activity from the following nerves: hypoglossal, phrenic, thyroarytenoid and triangularis sterni. Fictive breathing was spontaneous with carbon dioxide above the apnoeic threshold (end‐tidal PCO2, 32 +/‐ 4 mmHg) and fictive swallowing was induced by stimulating the internal branch of the left superior laryngeal nerve (SLN) continuously (0.2 ms pulse duration, 10 Hz). 2. In all ten animals, SLN stimulation evoked short bursts of thyroarytenoid and hypoglossal nerve activity indicative of fictive swallowing. In two of ten animals, respiration was inhibited completely during deglutition. In the other eight animals, fictive breathing and swallowing occurred simultaneously. 3. With SLN stimulation below threshold for eliciting swallowing, the respiratory rhythm decreased, the duration of inspiration did not change but the duration of expiration, especially stage II, increased. Integrated nerve activities indicated that the rate of rise and peak of phrenic nerve activity decreased, stage I expiratory activity of the thyroarytenoid and especially that of the hypoglossal nerve increased and stage II expiratory activity of the triangularis sterni nerve was suppressed completely. However, if inspired carbon dioxide was increased, i.e. hypercapnic ventilation, stage II expiratory activity remained partially during continuous SLN stimulation. 4. Fictive‐swallowing bursts occurred only at respiratory phase transitions. At the minimal stimulus intensity that evoked repetitive swallowing bursts, the pattern of interaction between breathing and swallowing central pattern generators was consistent for each animal (n = 7) but was different across animals. In four animals, fictive swallows occurred at the phase transition between stage II expiration and inspiration, at the transition between inspiration and stage I expiration in one animal; and in two other animals, at the transition between stage I and II of expiration. 5. The response to SLN stimulation accommodated during the stimulus train. Accommodation was evident in both the interswallow interval (ISI) which lengthened, and the interaction pattern which had fewer swallows per breath as the stimulus period progressed. In contrast to the ISI, characteristics of the fictive swallow did not accommodate. For example, duration of the swallow was constant, distributed over a narrow range throughout the stimulus train. 6. We conclude that the central pattern generators for swallowing and breathing interact. The pattern of interaction supports the three‐phase theory of respiratory pattern generation.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional magnetic stimulation of the respiratory muscles in dogs

This study assessed the ability of functional magnetic stimulation (FMS) to activate the respiratory muscles in dogs. With the animal supine, FMS of the phrenic nerves using a high‐speed magnetic stimulator was performed by placing a round magnetic coil (MC) at the carotid triangle. Following hyperventilation‐induced apnea, changes in volume (ΔV) and airway pressure (ΔP) against an occluded airway were determined. FMS of the phrenic nerves produced substantial inspired function (ΔV = 373 ± 20.5 mL and ΔP = −20 ± 2.0 cm H2O). After bilateral phrenectomies, maximal inspired ΔV (219 ± 12.2 mL) and ΔP (−10 ± 1.0 cm H2O) were produced when the MC was placed near the C6–C7 spinous processes, while maximal expired ΔV (−199 ± 22.5 mL) and ΔP (11 ± 2.3 cm H2O) were produced following stimulation near the T9–T10 spinous processes. We conclude: (1) FMS of either the phrenic or upper intercostal nerves results in inspired volume production; (2) FMS of the lower intercostal nerves generates expired volume production; and (3) FMS of the respiratory muscles may be a useful noninvasive tool for artificial ventilation and assisted cough in patients with spinal cord injuries or other neurological disorders.

Action of the intercostal muscles on the rib cage.

Recent studies suggest that the parasternal muscles (PA) are primarily responsible for rib cage expansion during eupneic breathing with a much lesser role played by the interosseous external intercostals (EI). The purpose of the present investigation was to assess the capacity of the EI to expand the rib cage during spontaneous breathing in the absence of coincident ipsilateral PA activation. In 9 anesthetized dogs, we measured PA EMG and length in the 3rd interspace and EI EMG and length in the 3rd and 4th interspaces. During resting breathing, each muscle was electrically active and shortened to a similar degree, approximately 3% of resting length. Following ipsilateral PA denervation (1st through 6th interspaces), the level of EI shortening in the 3rd and 4th interspaces was maintained, but with an increase in neural drive to these muscles. The parasternal muscle in the 3rd interspace lengthened during inspiration. Subsequent sequential denervation of EI in the 3rd and 4th interspaces resulted in their lengthening. In 4 additional animals, axial motion of the 4th rib was measured in the mid axillary line. Ipsilateral PA denervation had no significant effect on rib motion. External intercostal denervation (3rd interspace), on the other hand, had a substantial impact on rib motion, causing the 4th rib to move in the caudal direction during inspiration. Our results indicate that: (a) the EI of the lateral rib cage are capable of elevating the ribs during inspiration independent of PA contraction; (b) PA contraction contributes to EI shortening during eupneic breathing and (c) regional loss of muscle activation results in local rib cage distortion, suggesting that the upper rib cage has multiple degrees of freedom.

The role of midline ventral medullary structures in generation of respiratory motor high frequency oscillations

Lesions 1-2 mm deep in the midline of the ventral medulla (VM) abolished high frequency oscillations (HFO) in the respiratory motor output in cat and rabbit. Raising arterial pCO2 increased phrenic nerve activity to its prelesion level but did not restore HFO. We conclude that the neuronal pathways crossing the midline of the VM are crucial for reinforcement of respiratory activity and HFO generation.

Effects of diaphragm activation on airway pressure generation during lower thoracic spinal cord stimulation

Lower thoracic spinal cord stimulation (SCS) results in the generation of large positive airway pressures. The potential effects of diaphragm co-activation during SCS were investigated in 10 anesthetized dogs. Diaphragm compound action potentials (CMAPs) were present during SCS at the T10 and T12 levels. In group 1, airway (Paw) and trans-diaphragmatic (Pdi) pressures were monitored during supramaximal SCS before and after phrenicotomy. In group 2, pressures were monitored before and after C2 section to evaluate the potential influence of supraspinal centers. Following phrenicotomy in group 1, the reduction in Pdi during SCS was associated with increases in Paw. In group 2, diaphragm CMAPs and active Pdi increased following C2 section, while Paw fell. Following phrenicotomy, Paw increased significantly. In intact animals therefore, changes in Paw during SCS are affected by the interaction between inhibitory and excitatory influences on diaphragm activation. We conclude that lower thoracic SCS results in substantial diaphragm co-activation and secondary reductions in airway pressure generation.

Effects of Lung Volume on Parasternal Pressure‐Generating Capacity in Dogs

Previous studies have suggested that the optimum length for force generation of the parasternal intercostal (PS) muscles is well above functional residual capacity (FRC). We further explored this issue by examining the pressure‐generating capacity of the PS muscles as a function of lung volume in anaesthetized dogs. Upper thoracic spinal cord stimulation (SCS) was used to electrically activate the PS muscles. Changes in airway pressure and parasternal resting length (LR) during airway occlusion were monitored over a wide range of lung volumes during SCS. To assess the effects of parasternal contraction alone, SCS was performed following phrenicotomy and section of the external intercostal, levator costae and triangularis sterni muscles. With increasing lung volume, there were progressive decrements in the capacity of the PS muscles to produce changes in airway pressure. The relationship between PS pressure generation and lung volume was similar to a previous comparable assessment of the external intercostal muscles. The PS muscles shortened during passive inflation and also shortened further (by > 20% of LR) during SCS. Total shortening (passive plus active) increased progressively with increasing lung volume. Our results indicate that the capacity of the PS muscles to produce changes in airway pressure (a) falls progressively with increasing lung volume and (b) is similar to that of the external intercostal muscles. We speculate that the fall in PS pressure‐generating capacity is related, in part, to progressive reductions in end‐inspiratory length.

Bifurcation of the respiratory response to lung inflation in anesthetized dogs

Numerous studies have demonstrated the effect of lung volume on prolongation of duration of expiration (TE) with limited understanding of the TE shortening and termination of expiration as observed in newborn. In 14 dogs, the effects of varied onset of lung inflation during expiration on the TE were evaluated. When lung inflation was applied in the first part of expiration (20-60% of TE) TE was lengthened. However, in the second portion (60-80% of TE) of expiration, lung inflation either terminated or prolonged TE; whereas in the last portion of expiration (80-90% of TE), lung inflation tended to terminate expiration prematurely. The effects were abolished after bilateral vagotomy. We postulate that prolongation of TE relates to the Breuer-Hering inflation reflex, which increases the time needed for a passive expiration; whereas the ability to shorten TE could relate to Heads paradoxical reflex acting to initiate inspiration or to activate inspiratory motor activity to brake expiratory flow as occurs in the newborn.

PHASE·DEPENDENT TRANSIENT RESPONSES OF RESPIRATORY MOTOR ACTIVITIES FOLLOWING PERTURBATION OF THE CYCLE

Dynamics of an oscillator can be characterized by its behavior following a brief perturbing stimulus. The transient behavior of the oscillator returning to its steady state provides insights regarding the intrinsic properties of the oscillator. In Figure 1, the phrenic nerve activity represents the respiratory oscillation. The timing of the oscillator may be altered following the perturbing stimulus relative to that predicted from unperturbed breaths. This shift in timing is referred to as phase-resetting. We define old phase as the time from the onset of phrenic activity to the onset of the stimulus, and phase shift as the amount of resetting. The relationship between old phase and phase shift characterizes the respiratory oscillator, and called as a phase response curve. Description of phase-resetting characteristics have focused on only one phase of the respiratory oscillator, i. e., the onset or the offset of phrenic nerve activity (e. g. Paydarfar et al. 2 ). We monitored expiratory as well as inspiratory activities to examine the transient behavior of this oscillator in every phase.