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.     

Cartography of human diaphragmatic innervation: preliminary data

In humans, anatomy indicates that the phrenic nerve mainly arises from the C4 cervical root, with variable C3 and C5 contributions. How this translates into functional innervation is unknown. The diaphragm response to electrical stimulation of C3, C4 and C5 was described in three patients undergoing surgical laryngeal reinnervation with an upper phrenic root (surface chest electrodes at anterior, lateral and posterior sites; oesophageal and gastric pressures (Pes and Pga) to derive transdiaphragmatic pressure (Pdi)). Anatomically, the phrenic nerve predominantly originated from C4. Phrenic stimulation elicited motor responses at the three sites in the three patients, as did C4 stimulation. It produced Pdi values of 9, 11, and 14cmH(2)O in the three patients, respectively, vs. 9, 9, and 7cmH(2)O for C4. C3 stimulation produced modest Pdi responses, whereas C5 stimulation could produce Pdi responses close to those observed with C4 stimulation. These singular observations confirm the dominance of C4 in diaphragm innervation but suggest than C5 can be of importance.     

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.     

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.     

急性高碳酸血症对膈肌功能的影响

本文用电刺激犬膈神经（ＰＮＳ）、记录经膈压（Ｐｄｉ）－刺激频率（Ｆ）曲线、分析自主呼吸膈肌肌电频谱（ＥＭＧｄｉ）的方法，研究急性ＣＯ２潴留对膈肌功能的影响，并探讨ｐＨ值在其中的作用。发现：１．急性ＣＯ２潴留使Ｐｄｉ进行性下降、Ｐｄｉ－Ｆ曲线右移，ＥＭＧｄｉ频谱改变；２．维持正常的ｐＨ值可减轻Ｐｄｉ、ＥＭＧｄｉ的改变。提示急性ＣＯ２潴留严重损害膈肌功能，ｐＨ的变化于其中起重要作用。     

Ventilatory support by pacing of the conditioned diaphragm in quadriplegia

We provided full-time ventilatory support in five patients with respiratory paralysis accompanying quadriplegia by continuous electrical pacing of both hemidiaphragms simultaneously for 11 to 33 months through the application to the phrenic nerves of a low-frequency stimulus. The strength and endurance of the diaphragm muscle increased with pacing. Biopsy specimens taken from two patients who had uninterrupted stimulation for 6 and 16 weeks showed changes suggestive of the development of fatigue-resistant muscle fibers. When we compared these results with those of our earlier experience with intermittent unilateral stimulation of the diaphragm in 17 patients with respiratory paralysis, we found that continuous bilateral pacing using low-frequency stimulation appeared to be superior because of more efficient ventilation of both lungs, fewer total coulombs required to effect the same ventilation, and absence of myopathic changes in the diaphragm muscle. For patients with respiratory paralysis and intact phrenic nerves, continuous simultaneous pacing of both hemidiaphragms with low-frequency stimulation and a slow respiratory rate is a satisfactory method of providing full-time ventilatory support.     

Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure

We studied the effects of hypophosphatemia on diaphragmatic function in eight patients with acute respiratory failure who were artificially ventilated. Their mean serum phosphorus level was 0.55 +/- 0.18 mmol per liter (normal value, 1.20 +/- 0.10). The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic function was evaluated in each patient before and after correction of hypophosphatemia, which was achieved by administration of 10 mmol of phosphorus (as KH2PO4) as a continuous infusion for four hours. After phosphate infusion, the mean serum phosphorus level increased significantly (1.33 +/- 0.21 mmol per liter, P less than 0.0001). The increase in serum phosphorus was accompanied by a marked increase in the transdiaphragmatic pressure after phrenic stimulation (17.25 +/- 6.5 cm H2O as compared with 9.75 +/- 3.8 before phosphate infusion, P less than 0.001). Changes in the serum phosphorus level and transdiaphragmatic pressure were well correlated (r = 0.73). These results strongly suggest that hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure, and they emphasize the importance of maintaining normal serum inorganic phosphate levels in such patients.     

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.     

Effect of lung volume reduction surgery for emphysema on diaphragm function

Preoperative prediction of a successful outcome following lung volume reduction surgery (LVRS) for emphysema is imperfect. One mechanism could be improvement in respiratory muscle function yet controversy exists regarding the magnitude and mechanism of such an improvement. Therefore, we measured diaphragm strength in 18 patients before and after LVRS. Mean (S.D.) FRC fell from 6.53 to 5.40 l (p = 0.0001). Mean sniff transdiaphragmatic pressure increased from 76 to 87 cm H2O (14%, p < 0.03) and mean twitch transdiaphragmatic pressure (Tw Pdi) increased by 2.5 cm H2O at 3 months (12%, p = 0.03). There was a highly significant increase in twitch esophageal pressure (Tw Pes) (60%, p < 0.0001), which was maintained at 12 months (46% increase, p = 0.0004). No change was observed in quadriceps twitch tension in nine subjects in whom it was measured. After LVRS the ratio Tw Pes:Tw Pdi increased from 0.24 to 0.37 at 3 months (p = 0.0003) and 0.36 at 12 months (p = 008). Low values of Sn Pdi, Sn Pes, Tw Pes and a high RV/TLC ratio were the preoperative variables most predictive of improvement in shuttle walking distance. We conclude that LVRS improves diaphragm function primarily by alteration of lung volume. Patients with poor diaphragm function and high RV/TLC ratio preoperatively are most likely to benefit from the procedure.     

Neuromuscular function at hyperbaric pressures: pressure-anesthetic interactions.

Hydrostatic pressure and anesthetic agents exert mutually antagonistic effects, including pressure reversal of anesthesia and anesthetic amelioration of the high-pressure nervous syndrome. To clarify the cellular basis for these phenomena, twitch tension and electromyogram (EMG) were monitored in the indirectly stimulated isolated rat diaphragm. Compression to 137 atm increased twitch tension without changing EMG amplitude. Partial phrenic nerve block accompanied EMG depression induced by methoxyflurane and chloroform; pressure antagonized these effects. To examine subthreshold pressure effects, calcium concentration was decreased from 2.5 to 0.5 mM. Compression to 137 atm then reversibly decreased EMG amplitude, while enhancing twitch tension. In 0.5 mM calcium, methoxyflurane and chloroform depressed EMG amplitude before blocking phrenic nerve conduction; pressure to 137 atm produced additional depression. These results suggest that pressure enhances twitch tension by acting on excitation-contraction coupling or on the contractile mechanism. They also indicate that pressure may inhibit transmission at the neuromuscular junction, and they do not support synaptic transmission as a site of pressure-anesthetic antagonism.     

Effect of increased diaphragm activation on diaphragm power spectrum center frequency

Increased transdiaphragmatic pressure, reduced muscle blood flow, and increased duty cycle have all been associated with a reduction in the center frequency (CFdi) of the diaphragm's electrical activity (EAdi). However, the specific influence of diaphragm activation on CFdi is unknown. We evaluated whether increased diaphragm activation would result in a greater decline in the CFdi when pressure-time product (PTPdi) was kept constant. Five healthy subjects performed periods of intermittent quasi-static diaphragmatic contractions with a fixed duty cycle. In separate runs, subjects targeted transdiaphragmatic pressures (Pdi) by performing end-inspiratory holds with the glottis open and expulsive maneuvers at end-expiratory lung volume (EELV). Diaphragm activation and pressures were measured with an electrode array and balloons mounted on an esophago-gastric catheter, respectively. The EAdi, which was 25+/-8%(S.D.) of maximum at EELV, increased to 61+/-8% (P<0.001) when an identical Pdi (averaging 31+/-13 cmH2O) was generated at a higher lung volume (77% of inspiratory capacity). The latter was associated with a 17% greater decline in CFdi (P=0.012). In order to reproduce at EELV, the decrease in CFdi observed at the increased lung volume, a two-fold increase in PTPdi was required. We conclude that CFdi responds specifically to increased diaphragm activation when pressure-time product remains constant.     

膈神经的解剖及临床应用研究进展

目的:为膈神经移位治疗臂丛根性撕托伤,提供应用解剖学资料.方法:查阅与膈神经移位治疗臂丛根性撕托伤相关的解剖与临床文献资料,分析其应用价值和意义.结果:提供膈神经在颈部、胸腔内和膈肌内的走行、位置、毗邻及分支分布资料.结论:膈神经移位是用来治疗臂丛根性撕托伤的主要动力神经;臂丛探索仍是诊断臂丛损伤的全标准.     

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.     

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.     

Transcutaneous,dual channel phrenic nerve stimulator for diaphragm pacing

An electrical stimulation system for bilateral diaphragm pacing was constructed. The stimulator instrument comprises a transmitter and two implantable receivers and nerve electrodes. An optimised transcutaneous link system is described which utilises a radio frequency coupling to transmit both power and stimulus information to the receiver. The receiver unit was constructed in thick-film hybrid technology using bipolar and c.m.o.s. circuits and was packaged in a hermetically sealed metal case. The construction of the transmitter allows a high reliability, low power consumption and flexibility of the stimulus parameter control. A complete, bilateral phrenic nerve pacing system was implanted into a patient suffering from tetraplegia. It is concluded that electrical phrenic nerve stimulation to pace the diaphragm is capable of being used in clinical therapy.     

The effect of level of contraction on the electromyographic power spectrum of the diaphragm in pigs.

We investigated the relationship between the frequency components of myoelectric power spectra of the diaphragm and the level of diaphragmatic contraction in seven anaesthetized spontaneously breathing pigs. Electromyographic activity of the costal and crural portions of the diaphragm were recorded with fish-hook electrodes and the frequency-power spectra during inspiration were computed and expressed in terms of centroid frequency (fc). Diaphragmatic force was indirectly assessed as transdiaphragmatic pressure (Pdi) which was measured with balloon-catheter systems placed in the abdomen and oesophagus. The relationships between Pdi and costal and crural fc were assessed during brief (2 min) and incremental increases in diaphragmatic contraction, achieved by gradual occlusion of the inspiratory line of the breathing circuit. When Pdi was increased to 128, 191, 287 and 421% of the value measured during unobstructed breathing, costal and crural fc rose significantly in all animals because of an increase in the power of high-frequency components and a decline in the power of low-frequency components. Both costal and crural fc returned to control values within 5 min of the release of inspiratory occlusion. Our results indicate that the level of contraction is an important determinant of the diaphragmatic myoelectric power spectrum and should be taken into consideration when using power spectral analysis to diagnose diaphragmatic mechanical failure.     

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。     

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.     

胸腔镜下切取膈神经的应用解剖

目的对胸段膈神经的解剖关系进行了研究。为电视胸腔镜下切取全长膈神经进行移位治疗臂丛损伤奠定解剖学基础。方法选用新鲜尸体6具12侧,对膈神经及其周围器官进行解剖观察。结果胸腔内覆盖膈神经的胸膜较疏松,易于分离;膈神经从锁骨下缘到入肌点的长度为右侧(16.50±2.17)cm,左侧(23.00±2.50)cm;膈神经的血供主要来源于心包膈动脉,心包膈动脉的直径为(1.30±0.15)mm;在胸廓入口处膈神经、心包膈动脉及胸廓内动脉之间的解剖关系不恒定。结论膈神经在胸腔内的解剖特点适合进行电视胸腔镜下的全长游离。但在胸廓入口处,膈神经、胸廓内动脉及由胸廓内动脉发出的心包膈动脉解剖位置不恒定。在临床操作时,该区域的处理是整个手术的关键。