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Background: Diaphragm movement is essential for adequate ventilation, and when the diaphragm is adversely affected patients face lifelong positive-pressure mechanical ventilation or death. This report summarizes the complete worldwide multicenter experience with diaphragm pacing stimulation (DPS) to maintain and provide diaphragm function in ventilator-dependent spinal cord injury (SCI) patients and respiratory-compromised patients with amyotrophic lateral sclerosis (ALS). It will highlight the surgical experiences and the differences in diaphragm function in these two groups of patients., Methods: In prospective Food and Drug Administration (FDA) trials, patients underwent laparoscopic diaphragm motor point mapping with intramuscular electrode implantation. Stimulation of the electrodes ensued to condition and strengthen the diaphragm., Results: From March of 2000 to September of 2007, a total of 88 patients (50 SCI and 38 ALS) were implanted with DPS at five sites. Patient age ranged from 18 to 74 years. Time from SCI to implantation ranged from 3 months to 27 years. In 87 patients the diaphragm motor point was mapped with successful implantation of electrodes with the only failure the second SCI patient who had a false-positive phrenic nerve study. Patients with ALS had much weaker diaphragms identified surgically, requiring trains of stimulation during mapping to identify the motor point at times. There was no perioperative mortality even in ALS patients with forced vital capacity (FVC) below 50% predicted. There was no cardiac involvement from diaphragm pacing even when analyzed in ten patients who had pre-existing cardiac pacemakers. No infections occurred even with simultaneous gastrostomy tube placements for ALS patients. In the SCI patients 96% were able to use DPS to provide ventilation replacing their mechanical ventilators and in the ALS studies patients have been able to delay the need for mechanical ventilation up to 24 months., Conclusion: This multicenter experience has shown that laparoscopic diaphragm motor point mapping, electrode implantation, and pacing can be safely performed both in SCI and in ALS. In SCI patients it allows freedom from ventilator and in ALS patients it delays the need for ventilators, increasing survival.

Evidence for diaphragm injury in people with chronic obstructive pulmonary disease (COPD) has been reported, although the extent of injury and collagen accumulation post mortem have not previously been examined. In addition, it is not known whether the amount of injury and collagen are different in key regions of the diaphragm. The cross-sectional area of collagen and the percentage of abnormal myofibres in the post mortem diaphragm and psoas major were determined by computer-assisted image analysis of stained cross-sections of the diaphragm for collagen with picrosirius red and with haematoxylin and eosin for morphology. In the midcostal diaphragm of six subjects with COPD and six subjects with no significant respiratory disease, the COPD diaphragm displayed a greater cross-sectional area of collagen and percentage of abnormal myofibres (collagen: 24.2+/-1.0 versus 18.6+/-1.1%; injury: 28.4+/-7.2 versus 12.0+/-1.3%). In 18 patients with various respiratory conditions, the midcostal diaphragm displayed more collagen and abnormal myofibres than the crural diaphragm, while both costal and crural diaphragms displaying more collagen and abnormal myofibres than psoas major. This study reveals extensive injury and collagen accumulation in the chronic obstructive pulmonary diseased diaphragm, and reveals a regional pattern of injury and intramuscular collagen which may correspond to variations in diaphragm loading.

Upregulation of endothelial cell adhesion molecules, followed by an influx of granulocytes and macrophages, can contribute to exertion-induced skeletal muscle injury. The purpose of this study was to quantify circulating leukocyte subsets, diaphragm injury and infiltrating leukocyte subsets, and surface expression of vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1 in the diaphragm after inspiratory resistive loading (IRL). Eight New Zealand white rabbits underwent 1.5 h of IRL and seven control rabbits underwent a sham procedure. Blood samples, taken at baseline and 2, 6, 12, 24, 48 and 72 h after the onset of IRL or sham, showed that band cell counts had increased at 6 h post-IRL. Point counting of haematoxylin and eosin-stained cross-sections, sampled at 72 h post-IRL, showed greater injury in diaphragms from IRL rabbits compared with controls. Immunohistochemical processing showed increased expression of ICAM-1 and VCAM-1, and higher granulocyte and macrophage counts in IRL diaphragms than control diaphragms. Macrophages were the predominant inflammatory cells. Increased intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, and infiltration of granulocytes and macrophages may contribute to inspiratory resistive loading-induced diaphragm injury.

Three groups of NZW rabbits were studied to examine the role of free radical scavengers in preventing diaphragm injury produced by inspiratory resistive load (IRL): control, IRL, and scavenger groups. An IRL (Pao: 45-55 cm H2O) was applied to the IRL and the scavenger groups on Day 1. Free radical scavengers (polyethylene glycol superoxide dismutase, N-acetylcysteine, and mannitol) were given (intravenously) to the scavenger group both before and after the IRL. All rabbits were killed on Day 3 to collect diaphragms. Point counting H&E-stained diaphragm x-sections indicated that abnormal diaphragm muscle in the IRL group was significantly greater than control (p < 0.01). However, it was significantly lower in the scavenger group than the IRL group (p < 0.05) and it did not differ from control. In vitro diaphragm physiological studies found that the twitch tension (p < 0.05) and maximal tension (p < 0.01) in the IRL group were significantly lower than control. The maximal tensions (p < 0.05) in the scavenger group were lower than control. After the fatigue protocol, diaphragmatic contractility in the scavenger group was similar to control and was better maintained compared with the IRL group. We conclude that free radical scavengers can prevent the development of diaphragm injury as evidenced by histology but the protection of diaphragm function is limited.

The purpose of this study was to describe the nature of diaphragm injury, to quantify the injury and number of macrophages at the light microscopic level, and to determine their association with airflow obstruction in humans. Partial-thickness diaphragm biopsies were obtained from 21 subjects going for thoracotomy surgery (FEV(1): 74 +/- 34% predicted; range: 16 to 122% predicted). Cross sections cut from frozen diaphragm were processed with H&E or processed for immunohistochemistry using the monoclonal antibody Ber-MAC3 (DAKO Corp., Carpinteria, CA) to label macrophages. Area fractions (A(A)) or the proportions of the cross- sectional area were determined by point counting all viable fields of H&E-stained diaphragm cross sections. A(A) were 66.2 +/- 9.0% for normal muscle, 17.6 +/- 7.2% for abnormal muscle, and 16.3 +/- 4.2% for connective tissue. Percent predicted FEV(1) was inversely related to the A(A) of abnormal muscle (r = -0.53, p < 0.01) and directly related to the A(A) of normal muscle (r = 0.37, p < 0.05). The number of macrophages was not related to % predicted FEV(1) (mean +/- SD: 0.41 +/- 0.18/fiber; 52 +/- 19/mm(2)). We conclude that increasing severity of airflow obstruction is associated with an increased A(A) of abnormal diaphragm and a decreased A(A) of normal diaphragm.

Power spectra were derived from the diaphragm electromyogram (EMG) in anesthetized rabbits subjected to inspiratory resistive loading (IRL) with airway pressure swings of 40-60 cm H2O for 20 min to 2 h. Shifts in the centroid frequencies of the power spectra were found to be associated with the appearance of power spectral peaks in the range of 105-140 Hz, termed high-frequency oscillation, or HFO. Such peaks have been described before in phrenic nerve activity and in the diaphragm EMG. However, these peaks have not previously been connected with the shifts in centroid frequency seen during loaded breathing. Although such changes in frequency content have been taken to indicate fatigue in the diaphragm, we find that HFO can also cause a shift in centroid frequency during loaded breathing, an effect whose relation to fatigue has yet to be established.

The present study was designed to examine the effect of delayed diaphragm injury produced by inspiratory resistive loading (IRL) on diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm injury was assessed by the point-counting technique. Marked diaphragm injury was observed in the high-IRL group (p < 0.01), but no significant diaphragm injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease diaphragm force either before or after the high IRL on Day 3. We conclude that the diaphragm injury induced by high IRL has a significant impact on diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.

Limb muscles can be injured during and after vigourous contractions. However, this injury is most evident under specific conditions. The strength and type of muscle contraction as well as the contractile status of the muscle are important determinants of injury. The initiating event leading to muscle injury is not clearly understood but there are several leading theories. The respiratory muscles are of obvious importance to survival, and fatigue or injury to them has been hypothesized to be prevented by various mechanisms. One such mechanism is reduced activation by the central nervous system. In this review information on the neural activation of the breathing muscles during inspiratory loading is discussed and reveals that neural activation to the diaphragm, the main inspiratory muscle, is high. Previous studies investigating the presence of muscle fatigue immediately after such inspiratory loading have shown little evidence of it. However, based on information from limb muscles, delayed or secondary muscle injury might occur and could produce deleterious effects on respiratory muscle function. Recent evidence shows that chronic low intensity inspiratory loading can produce diaphragmatic injury (Reid et al.) and secondary or delayed muscle injury can occur three days after an acute period of high intensity inspiratory loading. The results reviewed in this article suggest that the respiratory muscles, specifically the diaphragm, are not spared from injury or the results of muscle injury. Diaphragmatic function during the period of secondary muscle injury is markedly impaired and thus respiratory muscle injury is a phenomenon that warrants further investigation.

Chronic or prolonged low-intensity loading of the inspiratory muscles has recently been shown to produce diaphragm injury. The present study was designed to examine whether an acute episode of inspiratory resistive loading (IRL) could produce secondary diaphragm inflammation and injury. On Day 1, three groups of anesthetized and intubated New Zealand White rabbits were subjected to moderate IRL (Pao of approximately 30 cm H2O), high IRL (Pao of approximately 45 cm H2O), or no load for 1.5 h. On Day 3, costal and crural diaphragms, parasternals, and gastrocnemius muscles were taken to assess injury by point counting. Normal muscle, abnormal and inflamed muscle, and connective tissue on hematoxylin and eosin-stained cross-sections were expressed as percentage of the total points for that cross-section. For the costal diaphragm, both the abnormal muscle (7.3 +/- 0.6% versus 1.1 +/- 0.2%; p < 0.001) and connective tissue (8.0 +/- 0.6% versus 5.7 +/- 0.2%; p < 0.01) in the high IRL group were higher than control, whereas in the moderate IRL group they were not significantly different from control. Total calpain-like activity was increased in the moderate IRL group but not in the high IRL group. Injury was observed in the parasternal muscles but to a lesser extent. No injury was observed in the gastrocnemius muscle. We conclude that secondary diaphragm injury occurs after acute IRL but only when the IRL exceeds the fatigue threshold.

The present study was designed to examine whether clenbuterol (CLEN) could reduce dexamethasone (DEX)-induced diaphragm dysfunction. We studied four groups of New Zealand white (NZW) rabbits, each receiving one of the following daily injections subcutaneously for 2 wk: saline (control), DEX 3 mg/kg, DEX 3 mg/kg + CLEN 2 mg/kg, and CLEN 2 mg/kg. Diaphragm fiber cross-sectional areas (CSA) were measured. Twitch transdiaphragmatic pressure (Pdi) and tetanic Pdi were measured during bilateral phrenic stimulation both before and after 60 min of inspiratory resistive loading (IRL). DEX produced a marked atrophy of type IIa and type IIb diaphragm fibers. This diaphragm atrophy was prevented by CLEN in the DEX plus CLEN group. CLEN alone increased CSAs of all three types of diaphragm fibers. Significant reductions in twitch Pdi and tetanic Pdi at all stimulation frequencies both before and after IRL were observed similarly in the DEX group as well as in the DEX plus CLEN group compared with the control animals. We conclude that DEX produces significant diaphragm atrophy and decreases diaphragmatic contractility. CLEN produces hypertrophy of the diaphragm and minimizes diaphragm atrophy induced by DEX, but it has no demonstrable protective effect on DEX-induced diaphragm dysfunction.

When highly motivated normal subjects perform maximal isocapnic ventilation, a substantial fall in ventilation is observed during the first minute associated with slowing of the maximum relaxation rate (MRR) of the inspiratory muscles. This suggests that these muscles are excessively loaded, raising the possibility that overt contractile failure of the diaphragm contributes to the fall in ventilation. We therefore investigated the effect of maximal isocapnic ventilation (MIV) on twitch transdiaphragmatic pressure (Pdi,Tw) elicited by cervical magnetic stimulation. We measured Pdi,Tw before and after 2 min MIV in nine normal subjects. Initial mean (SD) ventilation for the nine subjects was 196 (15) L.min-1 falling by 35% at 1 min. Pdi,Tw fell following MIV, at 10 min was reduced by 24%, and remained substantially reduced 90 min after MIV. No change in Pdi,Tw was observed during control studies in which subjects were studied with the same protocol but omitting MIV. We conclude that diaphragmatic contractility is reduced after 2 min maximal isocapnic ventilation and diaphragmatic fatigue may be a limiting factor in maximal ventilation in man.

The neural activation of the diaphragm during quiet and vigorously stimulated breathing has been hypothesized to be submaximal. In this study, we measured phrenic motoneuron firing rates during brief progressively increasing inspiratory resistive loads in anesthetized rabbits. We recorded activity in 68 phrenic motoneurons in 17 rabbits. We found that 40 of these axons were active during quiet breathing. Twenty-seven axons were silent during quiet breathing but began to fire as inspiratory loading progressed. The level of drive reflected by transdiaphragmatic pressure where silent phrenic motoneurons were recruited ranged from 5 to 45 cmH2O. Silent motoneurons showed significantly higher average rates of firing and significantly greater increases in firing rate as loading progressed (P < 0.01). The firing rate of both active and silent axons tended to plateau as rates approached 70-80 Hz. All motoneurons except for one, which may have been an afferent, were activated by inspiratory resistive loading. Inspiratory resistive loading activated phrenic motoneurons at high rates, and our results did not support the presence of significant numbers of unrecruited motoneurons.

Diaphragm strength can be assessed by measurement of transdiaphragmatic pressure (Pdi) in response to stimulation of the phrenic nerves. The length-tension relationship of the diaphragm can be studied by measuring twitch Pdi over the range of lung volume. Previous studies of the relationship between lung volume and diaphragm strength have used the technique of electrical stimulation of the phrenic nerves. In these studies, the phenomenon of twitch potentiation has not been taken into account. It has previously been shown that prior contraction of the diaphragm can greatly enhance the twitch response, thus affecting the measurements. The aim of this study was to investigate the relationship between unpotentiated twitch Pdi and lung volume for volumes ranging from residual volume (RV) to total lung capacity (TLC) in normal subjects. Great care was taken to avoid muscle potentiation. For this purpose, we stimulated the phrenic nerves with a magnetic stimulator. In addition, we used positive pressure to inflate the lungs to high lung volumes. The impact of twitch potentiation on the length-tension relationship was investigated by subjects making maximum inspiratory efforts prior to phrenic nerve stimulation. The unpotentiated twitch Pdi decreased in a linear fashion with increasing lung volume over the full range of vital capacity by 0.54 kPa.L-1. Potentiation increased twitch Pdi by 40% at FRC and the effect was similar, in absolute terms, at all lung volumes. In relative terms, the effect of potentiation became greater as lung volume increased, and more than doubled twitch Pdi at TLC. With increasing lung volume, there is a linear fall in unpotentiated twitch Pdi with a slope that is less steep, over the same range of absolute lung volume, than previously reported. When assessing diaphragm strength by the twitch technique, it is essential to control for lung volume and equally important to control for twitch potentiation.

To determine whether decreases in neural activation and/or neuromuscular transmission to the diaphragm contribute to ventilatory failure observed during inspiratory resistive loaded breathing, peak integrated activity of the intact phrenic nerve (ENGdi) and costal diaphragm (EMGdi), transdiaphragmatic pressure swings (Pdi) and evoked diaphragm compound action potentials (M-wave) were measured in anesthetized rabbits subjected to inspiratory resistive loads of varying intensities and duration breathing supplemental oxygen. Sustainable loads were studied for 4 h. Severe loads were applied in increments and studied for 50 min each. Loading resulted in parallel increases in ENGdi, EMGdi and Pdi that stabilized within 20 min. With severe loading, peak inspiratory pressure (Pao = -55 +/- 4 cm H2O) was maintained for 30 min after which there was a significant drop in inspiratory pressure (task failure). Despite hypoventilation and profound changes in blood gases, both activation (ENGdi) and neuromuscular transmission (ENGdi/EMGdi ratio or M-wave) were maintained throughout all loads even at task failure when a critical level of PaO2 (27 +/- 1 mm Hg) was reached. We conclude that neural activation and neuromuscular transmission to the diaphragm do not fail during inspiratory resistive breathing and discuss our findings in terms of current concepts of diaphragm fatigue and control of breathing in this model.

Background: Skeletal muscle twitch responses may be transiently increased by previous contractions, a phenomenon termed twitch potentiation. The aim of this study was to examine the extent and time course of diaphragmatic twitch potentiation and its relationship to both the magnitude and duration of the preceding voluntary diaphragmatic contraction., Methods: Twitch transdiaphragmatic pressure (PDI) was measured in six normal subjects, before and after voluntary diaphragm contractions of 100%, 75%, 50%, and 25% of maximum PDI (PDImax) sustained for five and 10 seconds., Results: Twitch PDI was significantly increased after 100%, 75%, and 50% contractions. Following maximal contractions sustained for 10 seconds the mean increase in twitch PDI was 52%. Following 50% contractions sustained for five seconds the mean increase in twitch height was 28%. In all runs twitch PDI returned to rested levels within 20 minutes., Conclusions: Twitch potentiation can be substantial, even following submaximal contractions, and must be taken into account when twitch pressure is used to assess diaphragm contractility.

Diaphragmatic shortening measured by sonomicrometry has been compared in the two major anatomic segments, costal and crural. Data obtained by videofluoroscopy found a variation in subsegmental shortening within segments (Sprung et al. J. Appl. Physiol. 67: 655-662, 1989). No reproducible pattern of subsegmental shortening has emerged, and the mechanisms leading to this subsegmental variation in shortening are unknown. Therefore, we compared subsegmental shortening in both segments of the diaphragm in seven supine pentobarbital-anesthetized dogs. Seven pairs of sonomicrometer transducers were implanted in the two segments, and subsegmental shortening during spontaneous breathing was measured. To determine potential mechanisms contributing to the variation in shortening, measurements were made during stimulated breathing, after epiphrenic stimulation, and during occluded breaths. We found electrical stimulation at physiological frequencies of 10 and 20 Hz reduced the variation in subsegmental shortening, whereas stimulated breathing did not. Occluded breaths showed a consistent decrease in the amount of shortening, particularly in the dome of the costal diaphragm, compared with shortening in the area of apposition. Comparison of shortening between segments revealed greater crural than costal shortening. We conclude that subsegmental variation in activation can contribute to variation in subsegmental shortening and that the afterload can effect shortening during occluded breaths.

In this study, we hypothesized that tumor necrosis factor alpha (TNF alpha) is an important mediator of sepsis-related impairment in diaphragm contractility (1-2). In 12 anesthetized, ventilated dogs, bipolar stimulating electrodes were placed on the phrenic nerves and diaphragm electromyographic activity (EMG) and shortening were recorded with needle electrodes and piezoelectric crystals, respectively. Transdiaphragmatic pressure (Pdi) was also recorded using esophageal (Pes) and abdominal balloon catheters (Pdi = Pab-Pes). Dogs were randomized to receive saline injection (n = 6), or TNF alpha 60 micrograms/kg (n = 6). All parameters were recorded hourly for 6 h. Mean arterial blood pressure decreased 1 h after infusion in TNF alpha animals (p < 0.05) with no significant change thereafter. Cardiac output increased early after TNF alpha infusion (p < 0.05) and remained at greater than baseline values at study termination. Diaphragm pressure generation and costal shortening decreased progressively from 3 to 6 h post TNF alpha infusion (p < 0.05) with no significant change in control animals. Compound diaphragm action potential in response to supramaximal phrenic stimulation decreased in TNF alpha animals (p < 0.01) with no significant change in control animals 3 and 6 h postinfusion. We conclude that TNF alpha infusion was associated with significant declines in isotonic and quasi-isometric diaphragm contraction and that this could be explained, at least in part, by impaired neuromuscular transmission.

In an earlier study (Road and Leevers (1988), J. Appl. Physiol. 65: 2283-2389), the application of continuous positive airway pressure (CPAP) produced a marked reduction in diaphragm initial length (LFRC) and tidal diaphragmatic shortening (%LFRC), tidal volume (VT) and transdiaphragmatic pressure swings (delta Pdi) in supine dogs after vagotomy. We postulated that the reduced diaphragmatic shortening was mainly a result of the decrease in diaphragm LFRC but an increase in afterload could not be excluded. In this study, we attempted to define the role of these two mechanisms during postural change. Eight, pentobarbital-anaesthetized, vagotomized dogs were studied in the supine position during CPAP and during postural change (tilting towards upright). As before, CPAP produced a prompt reduction in diaphragm LFRC and tidal %LFRC, VT and delta Pdi. Tilting produced similar decreases in crural diaphragm LFRC (23% from control values) as the weight of the abdominal contents was removed, but less decrease in costal LFRC (17% during CPAP compared to 10% during tilting). A given reduction in crural diaphragm initial length (15%) resulted in less tidal shortening during tilting compared to CPAP, whereas costal diaphragm shortening was similar at a given reduction in initial length (10%). Both CPAP and tilting reduced tidal volumes (47.8 +/- 5.1 and 56.5 +/- 3.1% of control), however, delta Pdi decreased less during tilting (20%) than CPAP (47%). There was no significant change in the level of diaphragmatic EMG with either CPAP or tilting.(ABSTRACT TRUNCATED AT 250 WORDS)

Active expiration is produced by the abdominal muscles and the rib cage expiratory muscles. We hypothesized that the relative contribution of these two groups to expiration would affect diaphragmatic length and, hence, influence the subsequent inspiration. To address this question we measured the respiratory muscle response to expiratory threshold loading in spontaneously breathing anesthetized dogs. Prevagotomy, the increase in lung volume (functional residual capacity) and decrease in initial resting length of the diaphragm were attenuated by greater than 50% of values predicted by the passive relationships. Diaphragmatic activation (electromyogram) increased and tidal volume (VT) was preserved. Postvagotomy, effective expiratory muscle recruitment was abolished. The triangularis sterni muscle remained active, and the increase in lung volume was attenuated by less than 15% of that predicted by the passive relationship. Diaphragmatic length was shorter than predicted. VT was not restored, even though costal diaphragmatic and parasternal intercostal electromyogram increased. During expiratory threshold loading with abdominal muscles resected and vagus intact, recruitment of the rib cage expiratory muscles produced a reduction in lung volume comparable with prevagotomy; however, diaphragmatic length decreased markedly. Both the rib cage and abdominal expiratory muscles may defend lung volume; however, their combined action is important to restore diaphragmatic initial length and, accordingly, to preserve VT.

Diaphragmatic length was measured by sonomicrometry and transdiaphragmatic pressure (Pdi) by conventional latex balloons in eight dogs anesthetized with pentobarbital sodium under passive conditions and during supramaximal phrenic stimulation. The passive length-pressure relationship indicates that the crural part of the diaphragm is more compliant than the costal part. With supramaximal stimulation the costal diaphragm showed a length-pressure relationship similar in shape to in vitro length-tension curves previously described for the canine diaphragm. The crural part has a smaller pressure-length slope than the costal part in the length range from 80% of optimum muscle length (Lo) to Lo. At supine functional residual capacity (FRC) the resting length (LFRC) of the costal and crural diaphragms are not at Lo. The costal part is distended to 105% of Lo, and crural is shortened to 92% of Lo. Tidal shortening will increase the force output of costal while decreasing that of the crural diaphragm. The major forces setting the passive supine LFRC are the abdominal weight (pressure) and the elastic recoil of the lungs. The equilibrium length (resting length of excised diaphragmatic strips) was 79 +/- 3.6% LFRC for the costal diaphragm and 87 +/- 3.9% LFRC for the crural diaphragm. Similar shortening was obtained in the upright position, indicating passive diaphragmatic stretch at supine LFRC.

The effects of fatigue on diaphragmatic contractility in vivo are unknown. In this study we used sonomicrometry to examine the velocity of shortening and lengthening and the amount of shortening in the fresh and fatigued canine hemidiaphragm (8 dogs) including the force generated. Fatigue was produced by epiphrenic stimulation of the left phrenic nerve; the right hemidiaphragm acted as the control. We found that 1) hemidiaphragmatic fatigue caused an increase in frequency with reduced tidal volume; 2) fatigue resulted in a near complete cessation of tidal shortening during spontaneous breathing; 3) there was an initial decrease in central activation (electromyogram) to the fatigued hemidiaphragm, an indication of central fatigue; 4) force-frequency curves showed a considerable and prolonged loss of the amount of shortening, velocity, and force generated by the fatigued hemidiaphragm during supramaximal stimulation, an indication of peripheral fatigue; and 5) during spontaneous breathing in the fatigued hemidiaphragm, tidal shortening remained reduced for up to 3 h, whereas in the right right hemidiaphragm tidal shortening and electromyographic activity did not change. We conclude that fatigue of a hemidiaphragm alters the spontaneous breathing pattern and produces profound modifications in its contractile properties without altering contralateral hemidiaphragmatic performance.

The use of sonomicrometry to study the mechanical properties of the diaphragm in vivo is presented. This method consists of the implantation of piezoelectric transducers between muscle fibers to measure the fibers' changes in length. Ultrasonic bursts are produced by one transducer upon electrical excitation and sensed by a second transducer placed 1-2 cm away. The time elapsed between the generation of the ultrasound burst and its detection is used to calculate the intertransducer distance. Excitation and sampling are done at 1.5 kHz and the output is a DC signal proportional to the length change between the transducers. Neither irreversible injury to the diaphragm nor regional differences within an anatomical part or segment were noted. Measurements were stable within the physiological range of temperature. We measured costal and crural length and velocity of contraction in anesthetized dogs during spontaneous breathing, occluded inspirations, passive lung inflation, and supramaximal phrenic nerve stimulation. We found that shortening during spontaneous breathing was 11 and 6% for crural and costal, respectively. The crural leads the costal in velocity of shortening. Supramaximal stimulation results in a velocity of shortening of 5 resting lengths X s-1. During an occluded inspiration crural shortens as much as in the nonoccluded breath, whereas costal shortens less. During passive lung inflation there is a nearly linear relationship between lung volume and diaphragm length; however, the relationships of chest wall dimensions with diaphragm length are nonlinear and cannot be described by any simple function. Some of the implications of these data on the present understanding of diaphragmatic mechanics are discussed.

Using sonomicrometry, we measured the in vivo tidal shortening and velocity of shortening of the costal and crural segments of the diaphragm in the anesthetized dog in the supine, upright, tailup, prone, and lateral decubitus postures. When compared with the supine position, end-expiratory diaphragmatic length varied by less than 11% in all postures, except the upright. During spontaneous breathing, the tidal shortening and the velocity of shortening of the crural segment exceeded that of the costal segment in all postures except the upright and was maximal for both segments in the prone posture. We noted the phasic integrated electromyogram to increase as the end-expiratory length of the diaphragm shortened below and to decrease as the diaphragm lengthened above its optimal length. This study shows that the costal and crural segments have a different quantitative behavior with body posture and both segments show a compensation in neural drive to changes in resting length.

The effect of lung inflation on chest wall mechanics was studied in 11 vagotomized pentobarbital sodium-anesthetized dogs. Diaphragmatic shortening (percent change from initial length at functional residual capacity, %LFRC) and transdiaphragmatic pressure swings (delta Pdi) were compared with control values over a range of positive-pressure breathing that produced a maximum increase in lung volume to 40% of inspiratory capacity. There was no change in the electromyogram of the diaphragm or parasternal intercostals during positive-pressure breathing. delta Pdi and tidal volume (VT) fell to 52 +/- 3.3 and 42.5 +/- 5% (SE) of control. This was associated with a reduction in the initial resting length of 13 +/- 1.9 and 21 +/- 2.2%LFRC (SE) in the costal and crural diaphragms, respectively. Tidal diaphragmatic shortening, however, decreased to 66 +/- 7 and 57 +/- 7 and the mean velocity decreased to 78 +/- 10 and 63 +/- 8% (SE) of control for the costal and crural diaphragms, respectively. We conclude that the reduction in diaphragmatic shortening is the main determinant of the reduced delta Pdi and VT during lung inflation and relate this to what is currently known about diaphragmatic contractile properties.

Decreased diaphragm activity has been demonstrated after cholecystectomy in humans (Am. Rev. Respir. Dis. 127: 431-436, 1983). To investigate the mechanism(s) of postoperative diaphragm dysfunction we have established a dog model. Three groups of mongrel dogs were studied under general anesthesia: six dogs received no surgery (control); nine dogs underwent upper abdominal surgery (cholecystectomy); and six dogs underwent lower abdominal surgery (pseudoappendectomy). Diaphragm function was assessed by changes in transdiaphragmatic pressure swings, the ratio of changes in gastric to esophageal pressure swings, and the ratio of changes in abdominal to rib cage diameters during quiet tidal breathing. In the upper abdominal surgery group there were significant postoperative decreases in all parameters of diaphragm function and an increase in minute ventilation and respiratory frequency. However, there were no significant postoperative changes in the parameters of diaphragm function in the control or lower abdominal surgery groups. These studies establish that general anesthesia is not responsible for the reduced diaphragm activity seen postoperatively and that diaphragm function is not affected by lower abdominal surgery in dogs.

In this study diaphragmatic length changes were measured during quiet breathing and during augmentation of breathing with hypoxia and hypercapnia in supine anesthetized dogs. The breathing pattern and the VT-TI relationship during hypoxia were different than those during hypercapnia. The crural diaphragm shortened more than the costal diaphragm with both stimuli, and the amount of shortening in relation to the tidal volume implied that there was considerable distortion of the chest wall during hyperventilation. The velocity of shortening of both parts of the diaphragm at similar levels of ventilation was greater during hypoxia than hypercapnia. The velocities found with hyperventilation suggested that force-velocity considerations did not reduce force generation. Hypoxic stimulation resulted in a reduction in the resting length of both parts of the diaphragm, and was associated with a positive shift in baseline pleural pressure which implied gas trapping. The large tidal diaphragmatic shortening found with augmented breathing and the shorter resting length with hypoxia indicated that length-force properties are important in force generation.