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.     

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.     

Foreword

High frequency spinal cord stimulation (HF-SCS) is a method of inspiratory muscle activation resulting in phrenic motoneuron activation via stimulation of spinal cord pathways. The specific pathways mediating this response, however, are unknown. The aim of this study was to assess the potential role of upper cervical (C1–C4) pre-phrenic interneurons (UCI) and localize the pathways in the thoracic spinal cord mediating activation of phrenic motoneurons during HF-SCS. In 7 anesthetized, spinalized (C1 level) dogs, HF-SCS was applied at the T2 level. Diaphragm EMG, inspired volume and airway pressure generation were monitored before and following sequential spinal cord sections at the C4 and C8 levels. Section at the C4 level and dorsal columns at C8 resulted in no significant changes. However, lateral funiculi section (C8 level) resulted in significant reductions in each parameter. We conclude that during upper thoracic HF-SCS, the phrenic motoneuron pools are activated via spinal pathways located in the lateral funiculus but UCI are not involved.     

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.     

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.     

右支气管封堵器在胸科单肺通气手术中的应用

目的　评估胸科行右侧肺叶单肺通气手术时,支气管封堵器应用的可行性及安全性。 方法　收集术中需要行右侧肺叶单肺通气的择期胸科手术患者36例,随机分为A、B两组,每组18例,A组插管方法采用传统双腔支气管法,B组采用支气管封堵器法。通过观察插管时间、插管前后生命体征变化、术中肺萎陷的质量、记录插管后、单肺通气20、40、60 min酸碱度（pH）、氧分压（pO2）、二氧化碳分压（pCO2）、及气道压Paw、患者术中出现低氧血症的例数及术后并发症等指标比较两种方法的安全性。 结果　单肺通气后所有患者Paw均升高,但随着时间的延长,B组明显低于A组（P＜0.05）;B术中发生低氧血症及术后发生声音嘶哑等并发症的例数均明显降低（P＜0.05）,差异有统计学意义。 结论　在行右侧肺叶单肺通气的胸科手术中,支气管封堵器法可以解决术中因双腔支气管对位不良而导致术中患者血氧降低的问题,且对气道刺激较小,是一种安全、有效的单肺通气方法。     

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.     

Total and regional lung volume changes during high-frequency oscillatory ventilation (HFOV) of the normal lung

The effect of high-frequency oscillatory ventilation (HFOV) settings on the distribution of lung volume (V(L)) with changes in mean airway pressure (Paw), frequency (f(R)) and tidal volume (V(T)) remains controversial. We used computer tomographic (CT) imaging to quantify the distribution of V(L) during HFOV compared to static continuous positive airway pressure (CPAP). In anesthetized, supine canines, CT imaging of the entire lung was performed during CPAP and HFOV at Paw of 5, 12.5 and 20 cm H(2)O, f(R)=5, 10, 15 Hz. We found small, statistically significant decreases compared with CPAP in total and regional V(L) during HFOV that were greatest at lower f(R) and Paw. Apex and base sub-volumes underwent changes comparable to the lung overall. Increases in f(R) were accompanied by increases in Pa(O)(2). These finding provide additional insight into the impact of HFOV settings on the distribution of V(L) and suggest that there is low risk of occult regional over-distention during HFOV in normal lungs.     

The effect of high cervical spinal cord stimulation on the expression of SP, NK-1 and TRPV1 mRNAs during cardiac ischemia in rat

Spinal cord stimulation (SCS) is used to reduce angina that accompanies cardiac ischemia, but little is known about the molecular mechanisms mediating this effect. We studied the expression of SP, neurokinin-1 (NK-1) receptor, and transient receptor potential vanilloid type 1 (TRPV1) mRNA in the rat spinal cord at thoracic 4 (T4), cervical 2 (C2) and caudal brain stem by RT-PCR during intermittent occlusion of the left anterior descending coronary artery (CoAO), during sustained SCS by itself at the C2 spinal segment, and during sustained SCS plus intermittent CoAO. Only SP mRNA was increased significantly in T4 and brainstem during CoAO, while SCS decreased the mRNA levels of SP, NK-1 and TRPV1 significantly in T4 and the brainstem. SCS attenuated the increase of SP and TRPV1 mRNA levels at T4 level induced by intermittent CoAO when the stimulation was applied prior to the initiation of the cardiac ischemia. These results support the role for SP as a putative neurotransmitter for the myocardial ischemia-sensitive afferent neuron signal to the spinal level. They suggest that modification of the ischemic cardiac nociceptive afferent signal by SCS involves a change in SP and TRPV1 expression.     

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.     

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.     

Neural co-activation as a yardstick of implicit motor learning and the propensity for conscious control of movement

Two studies examined EEG co-activation (coherence) between the verbal-analytical (T3) and motor planning (Fz) regions during a golf putting task. In Study 1, participants with a strong propensity to consciously monitor and control their movements, determined psychometrically by high scores on a movement specific Reinvestment Scale, displayed more alpha2 T3-Fz co-activation than participants with a weak propensity. In Study 2, participants who practiced a golf putting task implicitly (via an errorless learning protocol) displayed less alpha2 T3-Fz co-activation than those who practiced explicitly (by errorful learning). In addition, explicit but not implicit motor learners displayed more T3-Fz co-activation during golf putting under pressure, implying that verbal-analytical processing of putting movements increased under pressure. These findings provide neuropsychological evidence that supports claims that implicit motor learning can be used to limit movement specific reinvestment.     

Pressure-volume behaviour of the rat upper airway: effects of tongue muscle activation

Our hypothesis was that the simultaneous activation of tongue protrudor and retractor muscles (co-activation) would constrict and stiffen the pharyngeal airway more than the independent activation of tongue protrudor muscles. Upper airway stiffness was determined by injecting known volumes of air into the sealed pharyngeal airway of the anaesthetized rat while measuring nasal pressure under control (no-stimulus) and stimulus conditions (volume paired with hypoglossal (XII) nerve stimulation). Stimulation of the whole XII nerves (co-activation) or the medial XII branches (protrudor activation) effected similar increases in total pharyngeal airway stiffness. Importantly, co-activation produced volume compression (airway narrowing) at large airway volumes ( P < 0.05), but had no effect on airway dimension at low airway volumes. In comparison, protrudor activation resulted in significant volume expansion (airway dilatation) at low airway volumes and airway narrowing at high airway volumes ( P < 0.05). In conclusion, both co-activation and independent protrudor muscle activation increase airway stiffness. However, their effects on airway size are complex and depend on the condition of the airway at the time of activation.     

高气道压力机械通气致大鼠膈肌损伤的细胞凋亡机制

目的在前期试验中我们发现,给予大鼠40 cmH_2O气道压力控制通气20min对膈肌收缩功能有损伤。本研究进一步观察高气道压力控制通气下大鼠膈肌细胞超微结构的变化,并探讨膈肌细胞凋亡在呼吸机相关性膈肌损伤中的可能机制。方法将30只SD大鼠随机分为3组。给予40 cmH_2O气道压力控制通气20min组(HAP20min),5min组(HAP5min)、及对照组。HAP20min及HAP5min组设置50次,分的呼吸频率完全抑制了膈肌的电活动。机械通气后取膈肌组织经固定、常规超薄切片制备,进行超微结构观察。结果20min40cmH_2O气道压力控制通气可导致膈肌细胞发生凋亡的形态学改变,包括:核固缩,核膜模糊并有溶解。核内异染色质呈致密的块状,异染色质边聚呈环状,胞质内线粒体肿胀,部分嵴溶解。而HAP5min仅有细胞核的轻度改变。结论20min的高气道压力控制通气会造成大鼠膈肌肌纤维细胞凋亡,这可能是膈肌收缩功能下降的原因之一。     

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.     

Effects of mechanical load on flow, volume and pressure delivered by high-frequency percussive ventilation

High-frequency percussive ventilation (HFPV) has proved its unique efficacy in the treatment of acute respiratory distress, when conventional mechanical ventilation (CMV) has demonstrated a limited response. We analysed flow (V(dot)), volume (V) and airway pressure (Paw) during ventilation of a single-compartment mechanical lung simulator, in which resistance (R) and elastance (E) values were modified, while maintaining the selected ventilatory settings of the HFPV device. These signals reveal the physical effect of the imposed loads on the output of the ventilatory device, secondary to constant (millisecond by millisecond) alterations in pulmonary dynamics. V(dot), V and Paw values depended fundamentally on the value of R, but their shapes were modified by R and E. Although peak Paw increased 70.3% in relation to control value, mean Paw augmented solely 36.5% under the same circumstances (maximum of 9.4 cm H2O). Finally, a mechanism for washing gas out of the lung was suggested.     

The effects of changes in laryngeal airway CO2 concentration on genioglossus muscle activity in the anaesthetized cat

In the anaesthetized cat the larynx was isolated in situ, artificially ventilated and used to assess reflex effects exerted by respiration-related laryngeal stimuli on genioglossus electromyographic activity (Gg EMG) and respiratory frequency (RF). Phasic Gg EMG was not observed when the larynx was unventilated but was evoked, with a concurrent decrease in RF, when negative pressures or oscillatory pressures similar to those of normal ventilation were applied to the larynx. Increases in laryngeal airway CO2 concentration also enhanced Gg EMG and reduced RF. All reflex effects were abolished by bilateral section of the superior laryngeal nerves. We propose that negative intralaryngeal pressure and CO2 may act together to restore pharyngeal patency during obstructive apnoea.     

A necropsy study of distribution of petechiae in non-sudden infant death syndrome

The distribution of visceral petechiae in patients whose deaths were caused by upper airway obstruction and disorders other than sudden infant death syndrome (SIDS) has not been systematically studied. The clinical and necropsy records and microscopic slides of 50 such cases were retrospectively reviewed. In cases in which the cause of death could reasonably be ascribed to lethal upper airway occlusion, petechiae were found only in thoracic viscera. When death was apparently not preceded by terminal changes in intrathoracic pressure, petechiae were found in viscera above and below the diaphragm. These findings suggest that intrathoracic petechiae occur as a consequence of pressure changes within the chest and indirectly support the hypothesis that the terminal mechanism in SIDS is upper airway obstruction.     

Neonatal stress and abnormal hypercapnic ventilatory response of adult male rats: the role of central chemodetection and pulmonary stretch receptors

Neonatal maternal separation (NMS) is a form of stress that interferes with respiratory control development. At adulthood, the hypercapnic ventilatory response (HCVR) of male NMS rats is lower than controls both during wakefulness and anesthesia. To address the mechanisms underlying the respiratory phenotype of NMS rats, we first used phrenic nerve recording in anesthetised (urethane: 1.0 g/kg+isoflurane: 0.5%), vagotomised, and artificially ventilated (hyperoxic) animals, to test the hypothesis that the central chemodetection is altered by NMS. As no difference was observed between groups, we then tested the hypothesis that NMS affects respiratory modulation by pulmonary stretch receptors (PSRs). Experiments were performed on urethane/isoflurane anesthetised, spontaneously breathing rats (with vagi intact). The role of PSR and their implication was assessed during normo- and hypercapnia (+10 mm Hg above baseline) by the induction of a positive airway pressure (Paw). The slopes of the relationships between the ventilatory variables (frequency, amplitude, and minute activity) and the different levels of Paw in each group were compared between groups. During normocapnia, the decrease in breathing frequency induced by increasing Paw was greater in control than in NMS rats, thereby revealing that NMS reduces the Hering-Breuer reflex (HBR). During hypercapnia, however, the responses of control and NMS rats were similar indicating that the stimulation of chemoreceptors by CO(2) reduced the influence of stretch receptors on ventilation. These results indicate NMS does not affect central CO(2) chemosensitivity of this preparation but that differences in PSR function and/or signal integration contribute to the effects of NMS on respiratory regulation.     

Breathing pattern and stretch receptor activity during high frequency ventilation

In anaesthetized rabbits the effects of high frequency ventilation (HFV) on breathing pattern and on stretch receptor (SR) activity were examined in order to elucidate the mechanism underlying the inhibition of respiration during HFV. An attempt was undertaken to compare the effects of HFV with those of static lung inflations.HFV applied in frequencies between 5 Hz and 25 Hz and with peak airway pressure (Paw) between 5 and 15 cm H₂O led — proportionally to Paw — to a gradual prolongation of expiration up to an apnoea. Similar effects occurred during lung inflations, although at higher Paw than during HFV. HFV-induced apnoea was accompanied by a tonic phrenic and diaphragmatic activity which was absent during inflation-induced apnoea.In addition to the activity due to spontaneous breathing, during HFV the SR discharge rate increased with each positive airflow pulse particularly in the expiratory phase, whereas the inspiratory discharge rate was less affected. During static lung inflations there was a parallel increase of both inspiratory and expiratory SR activity, the expiratory discharge rate, however, remaining lower and the inspiratory discharge rate rising more than during HFV.It is concluded that the HFV-induced increase of expiratory SR discharge rate may account for the inhibition of spontaneous breathing during HFV. The persistence of phrenic and diaphragmatic activity during HFV-induced apnoea is thought to be due to activation of irritant receptors.