Diaphragmatic effects of selective resection of the upper phrenic nerve root in dogs

The aim of this study was to evaluate the effects on the diaphragm of upper phrenic nerve root resections in dogs. During laryngeal reinnervation, selective resections of the upper phrenic nerve root (C5) were performed unilaterally (right side, n=7; Group A) and bilaterally (n=6; Group B) and compared to non denervated animals (n=5). After 8 months, a diaphragmatic evaluation was performed: X-ray, EMG, transdiaphragmatic pressure (Pdi) after ipsi- and bilateral tetanic stimulation of the phrenic nerves and a bilateral histological study of five hemidiaphragmatic regions. EMG alterations were significantly more severe in Group B than in Group A, for the left (p<0.05) and right hemidiaphragms (p<0.01). No differences in the X-rays were noted between the three groups. The Pdi of the three groups after occlusion and phrenic nerve stimulations (unilateral and bilateral) were not statistically different. Histological data demonstrated that there were no differences in fibre irregularity, predominant fibre type or fibrosis between the three groups. Macroscopic and microscopic atrophy, which was mainly present on the anterior regions of the hemidiaphragms, was significantly higher in Group B than in Group A and undenervated dogs (p<0.05). In conclusion, resection of the upper phrenic nerve root of one phrenic nerve (right side) have limited effect on the diaphragm in dogs. However, resection of the upper phrenic nerve root on both sides resulted in a significant effect on the EMGs and histology of the entire diaphragm without any significant consequences on transdiaphragmatic pressure.     

Reproducibility of twitch and sniff transdiaphragmatic pressures

Twitch transdiaphragmatic pressure (Tw Pdi) measured with magnetic stimulation of the phrenic nerve is used to follow up patients and to assess the effect of clinical treatments on diaphragm function. However the reproducibility of Tw Pdi on different occasions has been little studied. We investigated 32 normal subjects, measuring Tw Pdi elicited by bilateral magnetic stimulation of the phrenic nerves on two to 14 occasions. Sniff transdiaphragmatic pressure (sniff Pdi) was also measured. The mean value of Tw Pdi and sniff Pdi were 28+/-5 and 134+/-24 cm H(2)O, respectively. The within subjects coefficient of variation was 11% for both Tw Pdi and sniff Pdi. We conclude that there is a variability of Tw Pdi and the variability of Tw Pdi is the same as that of sniff Pdi.     

Phrenic-to-phrenic inhibition and excitation in spinal cats

In decerebrate, C2-spinalized cats, stimulation of the C6-phrenic root produces a weak activation of phrenic motoneurons in the adjacent C5 segment in a few animals (23%). When phrenic motoneurons are electrically excited by testing stimulation applied to the spinal cord or internal intercostal nerve, the evoked responses recorded in a cervical phrenic root are partly inhibited by conditioning stimulation applied to another ipsilateral or contralateral cervical phrenic root. We therefore conclude that phrenic fibers exert both inhibitory and excitatory effects on adjacent phrenic motoneurons in the cervical spinal cord.     

Novel method for transdiaphragmatic pressure measurements in mice

The diaphragm muscle (DIAm) is responsible for breathing and determines the ability to generate both ventilatory and non-ventilatory behaviors. Size limitations of the mouse make transdiaphragmatic pressure (Pdi) measurement using a dual balloon system untenable. Adult C57BL/6J mice (n = 8) and C57BL/6 × 129 (n = 9), underwent Pdi measurements using solid-state pressure catheters spanning the thoracic and abdominal surfaces of the DIAm. Measurements were conducted during eupnea, hypoxia (10% O₂)–hypercapnia (5% CO₂), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths, sustained tracheal occlusion, and bilateral phrenic nerve stimulation. There was a difference in the Pdi generated across the range of ventilatory and non-ventilatory behaviors (p = 0.001). No difference in Pdi across behaviors was evident between mouse strains (p = 0.161). This study establishes a novel method to determine Pdi across a range of DIAm behaviors in mice that may be useful in evaluating conditions associated with reduced ability to perform expulsive, non-ventilatory behaviors.     

Superiority of nasal mask pressure over mouth pressure, as a surrogate of diaphragm twitch-related esophageal pressure, in healthy humans

Assessing diaphragm function is clinically and physiologically pertinent. It can rely on the measurement of pressure responses to phrenic stimulation. Combining mouth pressure (Pm) with cervical magnetic stimulation (CMS) is painless and easy to perform, but Pm-CMS poorly reflects esophageal pressure (Pes-CMS) because of poor pressure transmission across the airway. We reasoned that the mouth opening and neck flexion that are associated with the measurement of Pm-CMS would impair upper airway dynamics and further hinder pressure transmission. Therefore, we assessed the CMS-related pressure measured in a nasal mask (Pmask; mouth closed) without neck flexion as a possible surrogate of Pes-CMS, in 14 men and 3 women, age 24.5+/-2.2. Pes-CMS was 15.7+/-4.3 cmH2O, significantly higher than Pm-CMS (13.5+/-5.6 cmH2O, P<0.0001) but not different from Pmask-CMS (15.2+/-4.9 cmH2O). The concordance correlation coefficient was low (0.6808) between Pes-CMS and Pm-CMS. It was higher between Pes-CMS and Pmask-CMS (0.8730). Pm-CMS wrongly classified five subjects as abnormal (<10 cmH2O), versus 1 for Pmask and 5 for Pm (P=0.025). Passing and Bablok regressions found no difference between Pes-CMS and Pmask-CMS, but identified a systematic difference and a proportional error between Pes-CMS and Pm-CMS. We conclude that Pmask-CMS is a better surrogate of Pes-CMS than Pm-CMS.     

5-Hydroxytryptamine in the phrenic nerve diaphragm: evidence for its existence and release

Evidence is presented for the existence of 5-hydroxytryptamine (5-HT) within the phrenic nerve of the rat and its release following electrical stimulation. Contents of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the phrenic nerve and the indoleamine released into the bathing fluid were estimated fluorimetrically after isolation on Sephadex G-10 and/or solvent-solvent extraction. Bioassays of 5-HT were done on rat fundus strip. The phrenic nerve and the end-plate zone contains high levels of 5-HT (1.9 micrograms/g wet weight) and 5-HIAA (1.5 micrograms/g wet weight). The resting release of around 1 ng 5-HT/diaphragm/min was enhanced by 50% (1.5 ng 5-HT/diaphragm/min) upon supramaximal (2-4 V) electrical stimulation of 5 Hz. Phrenic nerve diaphragm prepared from the denervated and p-chlorophenylalanine (300 mg/kg/day i.p. for 3 days) treated rats failed to release 5-HT confirming the neuronal origin and the identity of the indoleamine respectively. Furthermore, methysergide, an antagonist of 5-HT in rat fundus strip, blocked the response obtained by the sample on it. A modulatory role of 5-HT in the phrenic nerve diaphragm of the rat is envisaged from the present study.     

Thalamocortical projections activated by phrenic nerve afferents in the cat

This study identified thalamocortical projections activated by respiratory afferents. Cortical evoked potentials were recorded in the right primary somatosensory cortex of the cat following electrical stimulation of the left C5 root of the phrenic nerve. The majority of primary sites were located in the vicinity of the postcruciate dimple, in area 3a near the 3a/3b border, corresponding to the trunk region of the cortical body map. Retrograde fluorescent tracers injected at the sites of primary activation produced labeled cells in the oralis nucleus of the ventroposterior complex [4]. Control injections made in adjacent cortical areas not activated by phrenic stimulation resulted in labeling in the ventroposterior complex which did not overlap that seen with injections of primary activation sites. We conclude that respiratory muscle afferents in the phrenic nerve elicit activity in the trunk region of primary somatosensory cortex via specific thalamocortical projections originating in the oralis portion of the thalamic ventroposterior complex.     

Extra-segmental reflexes derived from intercostal afferents: phrenic and laryngeal responses

1. Phrenic and recurrent laryngeal efferent responses were evoked by brief tetani or single shocks to the cut external intercostal nerves of anaesthetized cats. The reflexes derived from middle thoracic segments (T5 and 6) were compared with those emanating from caudal thoracic segments (T9 and 10).2. During inspiration, middle intercostal nerve stimulation transiently inhibited the spontaneous discharge in both efferent neurograms, whereas stimulation of caudal intercostal nerves facilitated phrenic discharge and usually inhibited recurrent laryngeal activity.3. During expiration, stimulation at either thoracic level enhanced recurrent laryngeal discharge while provoking little or no phrenic response.4. Superficial lesions of the lateral cervical cord, ipsilateral to the stimulus sites, above or below the phrenic outflow, eliminated all reflex responses except the phrenic response to caudal thoracic stimuli. Similarly, in the spinal animal, middle intercostal afferents could not be shown to decrease phrenic excitability. Caudal intercostal afferents cause phrenic excitation by a spinal reflex.5. Group I afferents of the mid-thoracic segments and group II afferents of the caudal thoracic segments initiate these extra-segmental reflexes.6. The recurrent laryngeal responses manifest, for the most part, changes in the discharge of fibres innervating the posterior cricoarytenoid muscle. The responses fit the overall pattern of response to middle intercostal nerve stimulation, namely, inhibition of inspiratory muscles and excitation of expiratory muscles. Intercostal afferent stimulation also activated the laryngeal adductor muscles.7. The results support the view that intercostal mechanoreceptors initiate an array of extra-segmental respiratory reflexes, including spinal and supraspinal arcs. The simplest way to account for the various responses to stimulation of middle intercostal afferents is to postulate a reflex involving supraspinal respiratory neurones.8. The observed reflexogenic differences correlate with anatomical differences between the middle and caudal ribs. Possible functional implications of this relationship are discussed.     

Diaphragm motor unit recruitment in rats

We hypothesized that considerable force reserve exists for the diaphragm muscle (DIAm) to generate transdiaphragmatic pressures (Pdi) necessary to sustain ventilation. In rats, we measured Pdi and DIAm EMG activity during different ventilatory (eupnea and hypoxia (10% O₂)–hypercapnia (5% CO₂)) and non-ventilatory (airway occlusion and sneezing induced by intranasal capsaicin) behaviors. Compared to maximum Pdi (Pdi_max generated by bilateral phrenic nerve stimulation), the Pdi generated during eupnea (21 ± 2%) and hypoxia–hypercapnia (28 ± 4%) were significantly less (p < 0.0001) than that generated during airway occlusion (63 ± 4%) and sneezing (94 ± 5%). The Pdi generated during spontaneous sighs was 62 ± 5% of Pdi_max. Relative DIAm EMG activity (root mean square [RMS] amplitude) paralleled the changes in Pdi during different ventilatory and non-ventilatory behaviors (r² = 0.78; p < 0.0001). These results support our hypothesis of a considerable force reserve for the DIAm to accomplish ventilatory behaviors. A model for DIAm motor unit recruitment predicted that ventilatory behaviors would require activation of only fatigue resistant units.     

Hypothesis that vagal reinervation of diaphragm could sensitise it to electrical stimulation

The hypothesis proposed is that restoration of functional capacity of denervated diaphragm may be achieved by reinervating it with vagus nerve. Following trauma, carcinomatose infiltration, and/or large thoracic surgery and neck surgery, phrenic nerve is frequently injured. Reinervation even in the most favourable conditions would not follow and diaphragm would rest permanently denervated and paralysed. This results in unilateral or bilateral paralysis of diaphragm. In principle, intermittent electrical stimulation of the phrenic nerve or diaphragm could elicit regular diaphragm contractions and maintain satisfactory respiration. While this technique could be used in upper motor neurone injury, in lower motor neurone injury and denervated diaphragm, that imposes too high electrical resistance, direct diaphragm pacing is practically impossible. In these cases, long term artificial ventilation is often necessary. Nevertheless, those patients are at high risk to suffer from atelectasis and respiratory infections. We project a hypothesis that reinervation of denervated diaphragm by vagus nerve could re-establishes its sensitivity to intramuscular electrical stimulation and may allow stimulation of the diaphragm by implanted pace-maker electrodes. An appropriate electrical stimulation might then be possible and diaphragm pacing could replace prolonged artificial ventilation in those patients. Restoration of functional capacity of denervated diaphragm could open a perspective for long term diaphragm pacing in patients with irreversible phrenic nerve injury and diaphragm paralysis.     

The accessory phrenic nerve in the rat

Summary Reinnervation studies of the diaphragm led us to reinvestigate the normal anatomy of the phrenic nerve of the rat. The phrenic nerve originates from the cervical nerve roots C₄ and C₅. In 16 out of 19 normal rats an accessory phrenic nerve was observed receiving its segmental fibres from C₆. The number of myelinated axons of the accessory phrenic nerve varied from 41 to 101 (mean: 64.3, i.e. about 15% of the average number of axons in the common phrenic nerve). The accessory phrenic nerve innervates the dorsal part of the costal and the lateral part of the crural region, whereas the remaining parts of the hemidiaphragm are supplied by the segments C₄ and C₅. There is no evidence for any additional contribution to the motor innervation of the diaphragm from intercostal nerves.Direktor: Prof. Dr. W. ZenkerThis study was supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich.     

Restoration of respiratory muscle function following spinal cord injury. Review of electrical and magnetic stimulation techniques

Respiratory complications are a leading cause of morbidity and mortality in patients with spinal cord injury. Several techniques, currently available or in development, have the capacity to restore respiratory muscle function allowing these patients to live more normal lives and hopefully reduce the incidence of respiratory complications. Bilateral phrenic nerve pacing, a clinically accepted technique to restore inspiratory muscle function, allows patients with ventilator dependent tetraplegia complete freedom from mechanical ventilation. Compared to mechanical ventilation, phrenic nerve pacing provides patients with increased mobility, improved speech, improved comfort level and reduction in health care costs. The results of clinical trials of laparoscopically placed intramuscular diaphragm electrodes suggest that diaphragm pacing can also be achieved without the need for a thoracotomy and associated long hospital stay, and without manipulation of the phrenic nerve which carries a risk of phrenic nerve injury. Other clinical trials are being performed to restore inspiratory intercostal function. In patients with only unilateral phrenic nerve function who are not candidates for phrenic nerve pacing, combined intercostal and unilateral diaphragm pacing appears to provide benefits similar to that of bilateral diaphragm pacing. Clinical trials are also underway to restore expiratory muscle function. Magnetic stimulation, surface stimulation and spinal cord stimulation of the expiratory muscles are promising techniques to restore an effective cough mechanism in this patient population. These techniques hold promise to reduce the incidence of respiratory tract infections, atelectasis and respiratory failure in patients with spinal cord injury and reduce the morbidity and mortality associated with these complications.     

Morphological study of the ansa cervicalis and the phrenic nerve

Morphological features of ansa cervicalis and phrenic nerve were studied in 106 cadavers. Ansa cervicalis was located medial to the internal jugular vein in 63% (medial type) and lateral to the vein in 33.7% (lateral type). Ansa cervicalis was derived from a combination of C1-C4 spinal segments, with C1-C3 being the most frequent pattern (87.5%). In >60% the ansa was bilaterally symmetrical. The distribution of medial and lateral types was equal on left and right sides of the body. The segmental composition of the inferior root was higher in the medial type and also on the left side of the body. In the lateral type the branches that formed the inferior root frequently (75%) formed a common trunk before joining the superior root, but in 74.8% of the medial type they joined the superior root independently. The phrenic nerve was derived from C4 and C5 in 52%. The C4 segment was present in the phrenic nerve in all cases except one. Additional phrenic components that pass anterior to the subclavian vein were defined as accessory phrenic nerves and found in 28.7%, while those passing posterior to the same vein were defined as secondary phrenic nerves (19.8%). Most of the accessory phrenic nerves contained a C5 segment and the nerve to subclavius was the commonest source. Various relationships between the ansa cervicalis and the phrenic nerve are investigated and, based on these findings, two separate classifications for the two nerves are suggested.     

膈神经传导时间在麻醉复苏中的应用

目的:探讨膈神经传导时间(PNCT)在麻醉复苏过程中对膈肌功能的监测作用。方法: 对8例手术病人观察全麻使用肌松药前后颤搐性跨膈压(Pdi_(t))和PNCT的变化。结果: 8例手术病人在全麻前:Pdi(t)为(23.7±2.4) cmH₂O,左、右侧PNCT分别为(5.7±1.3) ms和(5.6±0.9) ms;全麻使用肌松药后:Pdi_(t)下降到(11.5±3.4) cmH2O(下降率51.5%,P＜0.01),而左、右侧PNCT则分别延长为(6.1±1.3)ms和(6.4±0.6)ms,并随Pdi_(t)的恢复而逐步缩短。结论:肌松药诱发膈肌无力和引起双侧PNCT延长,且PNCT随着Pdi_(t)的恢复而缩短; PNCT的测定有助于间接监测全麻使用肌松药期间膈肌肌力的动态变化。     

Comparison of the hyperglycaemic and glycogenolytic responses to catecholamines with those to stimulation of the hepatic sympathetic innervation in the dog

1. The effects of stimulation of the splanchnic innervation to the adrenal medullae, in dogs with cut hepatic nerves, were compared with those obtained previously in response to splanchnic and hepatic nerve stimulation in adrenalectomized dogs.2. Maximal stimulation of both adrenal medullae via the splanchnic innervation (20 c/s for 9 min), in dogs with cut hepatic nerves, produced closely similar hyperglycaemic and glycogenolytic responses to those obtained previously in adrenalectomized dogs with intact hepatic nerves.3. The rise in plasma glucose concentration in response to maximal stimulation of the adrenal medullae in dogs with intact hepatic nerves was found to be comparable to that which occurs in response to maximal stimulation of the hepatic sympathetic innervation alone. In contrast, the rise in haematocrit during maximal stimulation of the entire splanchnic innervation was substantially greater than that observed after removal of both adrenal glands.4. The output of adrenaline and noradrenaline from the left adrenal gland was determined during maximal stimulation of the left splanchnic nerve (20 c/s for 9 min). These results were then used to compute doses of the two amines which would reproduce the output of catecholamines from both glands under such conditions. The extent of the rise in mean plasma glucose concentration in response to these infusions was similar to that produced by maximal stimulation of both adrenal glands, but the duration of hyperglycaemia and depletion of liver glycogen were significantly less.5. Stimulation of the splanchnic innervation was found to produce an initial ;surge' in the release of catecholamines from the adrenal medullae, followed by a rapid decline in output when stimulation was continued for longer than 30 sec. Evidence was obtained which showed that this pattern of release is well suited to produce rapid mobilization of liver glycogen.6. Comparable changes in plasma glucose concentration occurred in response to stimulation of either the adrenal medullae or the sympathetic innervation to the liver at low frequency (2.0 c/s for 5 min). Stimulation of both pathways simultaneously, at the same frequency, produced smaller responses.7. Intramesenteric infusions of noradrenaline at 1.0 mug.kg(-1) min(-1) for 5 min produced comparable changes in plasma glucose concentration to those observed during stimulation of either pathway alone at low frequency. The mean plasma noradrenaline concentration of portal blood was raised by between 92 and 105 ng/ml. during these infusions.8. It is concluded that stimulation of either the splanchnic innervation to the liver, or of both adrenal medullae, at high frequency (20 c/s for 9 min) represents a supramaximal stimulus for hepatic glycogenolysis. Comparison of the responses to stimulation at low frequency (2.0 c/s for 5 min) suggests that the hepatic glycogenolytic mechanism is equally sensitive to stimulation via either route in this species.     

Usefulness of phrenic nerve stimulation to measure upper airway collapsibility in normal awake subjects

Upper airway (UA) collapsibility can be characterized during sleep by looking at the changes in inspiratory flow limitation (IFL) with changing nasal pressure. IFL can be induced during wakefulness using phrenic nerve stimulation (PNS) applied during exclusive nasal breathing. The aim of the study was to evaluate the possibility of measuring UA critical pressure (Pcrit) in normal awaked subjects using electrical PNS (EPNS) or bilateral anterior magnetic phrenic stimulation (BAMPS). Instantaneous flow, esophageal (Peso) and mask pressures (Pmask), and genioglossal (GG) end-expiratory EMG activity were recorded in 13 normal subjects (4F, 9M) with randomly changing Pmask (0 to -20 cmH2O). For each trial, we examined the relationship between maximal inspiratory flow (Vtmax) of IFL twitches and the corresponding Pmask. Pcrit could be determined in 12 subjects (mean -33.5 +/- 16.3 cmH2O). No difference in Pcrit values was found between the EPNS and BAMPS methods but the strength of the Vtmax/Pmask relationship was higher with BAMPS. GG end-expiratory EMG activity increased with decreasing Pmask but no significant relationship was found between the slope of the GG end-expiratory EMG activity/Pmask relationship and Pcrit. We conclude that: (1) Pcrit can be measured during wakefulness in normal using PNS: (2) Pcrit measurements may be easier and more reliable with BAMPS than EPNS: and (3) Pcrit does not seem to be influenced by the pressure-related changes in GG end-expiratory EMG.     

Synaptic inhibition of cat phrenic motoneurons by internal intercostal nerve stimulation.

Intracellular recordings from 65 phrenic motoneurons (PMNs) in the C5 segment and recordings of C5 phrenic nerve activity were made in 27 pentobarbitone-anesthetized, paralyzed, and artificially ventilated adult cats. Inhibition of phrenic nerve activity and PMN membrane potential hyperpolarization (48/55 PMNs tested) was seen after stimulation of the internal intercostal nerve (IIN) at a mean latency to onset of 10.3 +/- 2.7 ms. Reversal of IIN-evoked hyperpolarization (n = 14) by injection of negative current or diffusion of chloride ions occurred in six cases, and the hyperpolarization was reduced in seven others. Stimulation of the IIN thus activates chloride-dependent inhibitory synaptic inputs to most PMNs. The inhibitory phrenic nerve response to IIN stimulation was reduced by ipsilateral transection of the lateral white matter at the C3 level and was converted to an excitatory response by complete ipsilateral cord hemisection at the same level. After complete ipsilateral hemisection of the spinal cord at C3 level, stimulation of the IIN evoked both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in PMNs (n = 10). It was concluded that IIN stimulation can evoke both excitatory and inhibitory responses in PMNs using purely spinal circuitry, but that excitatory responses are normally suppressed by a descending pathway in intact animals. Fifteen PMNs were tested for possible presynaptic convergence of inputs in these reflex pathways, using test and conditioning stimuli. Significant enhancement (>20%) of IPSPs were seen in seven of eight IIN-evoked responses using pericruciate sensorimotor cortex (SMC) conditioning stimuli, but only one of five IIN-evoked responses were enhanced by superior laryngeal nerve (SLN) conditioning stimuli. The IIN-evoked IPSP was enhanced in one of two motoneurons by stimulation of the contralateral phrenic nerve. It was concluded that presynaptic interneurons were shared by the IIN and SMC pathways, but uncommonly by other pathways. These results indicate that PMNs receive inhibitory synaptic inputs from ascending thoracocervical pathways and from spinal interneurons. These inhibitory reflex pathways activated by afferent inputs from the chest wall may play a significant role in the control of PMN discharge, in parallel with disfacilitation following reduced activity in bulbospinal neurons projecting to PMNs.     

Effects of stimulation of phrenic afferent fibers on medullary respiratory neurons in cat

The effects of electrical stimulation of both cervical branches (C5 and C6) of the right phrenic nerve on medullary respiratory neuron activity were studied in anesthetized, spontaneously breathing cats. In 14 cats, the stimulation of the thin phrenic afferents had no effect on the inspiratory duration and evoked excitatory or inhibitory responses in only 3/86 inspiratory neurons tested. In 3 cats, the stimulation decreased the inspiratory duration and 26/26 inspiratory neurons showed a shortened discharge without modification of their discharge frequency. Although the effects of the stimulation were not analysed by averaging techniques, it is concluded that phrenic afferents do not exert an important control on the medullary respiratory neuron discharge.     

An electron microscopic analysis of the left phrenic nerve in the rat

In this electron microscopic study, the axonal categories in the left phrenic nerve at its entrance to the diaphragm have been determined. At a level 3 mm rostral to the diaphragm, the left phrenic nerve contains approximately 700 axons: 57% are myelinated and 43% are unmyelinated. The dorsal root ganglion cells give rise to 31% of the myelinated axons and the ventral root contributes 69%. Of the unmyelinated axons, the dorsal root ganglion cell contributes 59%, the cervical sympathetic chain 24%, and 17% course through the ventral roots. These ventral root unmyelinated axons are presumably preganglionic efferents since the proximal stump of the ventral root showed no decrease in unmyelinated axons after ventral rhizotomy.     

Effects of ischemic phrenic nerve root ganglion injury on respiratory disturbances in subarachnoid hemorrhage: an experimental study

Introduction

Phrenic nerves have important roles on the management of respiration rhythm. Diaphragm paralysis is possible in phrenic nerve roots ischemia in subarachnoid hemorrhage (SAH). We examined whether there is a relationship between phrenic nerve root ischemia and respiratory disturbances in SAH.

Material and methods

This study was conducted on 5 healthy control and 14 rabbits with experimentally induced SAH by injecting autologous blood into their cisterna magna. Animals were followed up via monitors for detecting the heart and respiration rhythms for 20 days and then decapitaed by humanely. Normal and degenerated neuron densities of phrenic nerve root at the level of C4 dorsal root ganglia (C4DRG) were estimated by Stereological methods. Between the mean numerical density of degenerated neurons of C4DRG and respiratory rate/minute of groups were compared statistically.

Results

Phrenic nerve roots, artery and diaphragm muscles degeneration was detected in respiratory arrest developed animals. The mean neuronal density of C4DRG was 13272 ±1201/mm3 with a mean respiration rate of 23 ±4/min in the control group. The mean degenerated neuron density was 2.240 ±450/mm³ and respiration rhythm was 31 ±6/min in survivors. But, the mean degenerated neuron density was 5850 ±650/mm³ and mean respiration rhythm was 34 ±7/min in respiratory arrest developed animals (n = 7). A linear relationship was noticed between the degenerated neuron density of C4DRG and respiraton rate (r = –0.758; p < 0.001).

Conclusions

Phrenic nerve root ischemia may be an important factor in respiration rhythms deteriorations in SAH which has not been mentioned in the literature.