Breathing pattern in sarcoidosis and idiopathic pulmonary fibrosis.

We measured the volume and time components of the breathing cycle together with the P.1 in 16 sarcoidosis and 9 IPF patients. Patients in the IPF group were older, and their lung functions revealed a more restrictive pattern with small TLC, VC, and higher elastance values. We observed that in the two groups of patients there was a significant correlation between VT, f, and P.1 and lung elastance, and that the stiffer IPF patients had higher drive parameters. Hence, the main factor affecting the breathing pattern in both groups is the influence of the elastic load on the control of breathing. A significant relationship was also found between %VD/VT and elastance. We then compared the f values of the 16 sarcoidosis and 9 IPF patients with those of elastically loaded normal subjects. At equivalent levels of elastance, even though the patients and the normals showed qualitatively similar changes, the patients tended to have higher frequencies for the equivalent elastic load. In conclusion, ventilatory and drive parameters in interstitial lung diseases increased as a function of the elastic load, this load being greater in IPF than in sarcoidosis. Inflammation may stimulate the vagal receptors to increase the frequency of breathing, but this requires further study.

Optimal diaphragmatic blood perfusion.

The intrabreath time course of phrenic artery blood perfusion (Qpha) was studied in five anesthetized dogs. The diaphragm was paced with submaximal levels of stimulation at various duty cycles (DC) to achieve tension-time index below and above the fatigue threshold (0.03-0.60). Left Qpha was measured via Doppler technique during control (inactive diaphragm) and during two submaximal levels of bilateral phrenic nerve stimulation sustained for 1 min. Measurements were done when Qpha reached steady state in each run. The frequency of pacing of each run was 10/min, and the DC ranged from 0.1 to 0.9 in 0.1 increments. Shortening of costal and crural segments was measured by sonomicrometry. It was found that Qpha during the diaphragmatic contraction phase (QphaC) was a sigmoidal function of DC and was not affected by the levels of transdiaphragmatic pressure (Pdi) explored (34-64% of maximal Pdi). Qpha during the diaphragmatic relaxation phase (QphaR) was a parabolic function of the DC, reaching an optimal value at DC of approximately 0.3 at any given Pdi. QphaR increased significantly with the preceding level of Pdi. QphaT (the sum of QphaC and QphaR) was a parabolic function of DC, reaching peak values at DC of 0.4-0.6 and then decreasing. This function was similar at two levels of Pdi. Post-pacing hyperemia was directly related to tension-time index greater than 0.20.

Automatic assessment of electromyogram quality.

Power spectrum analysis of the diaphragm electromyogram (EMGdi) is time consuming, and no criteria have been developed to objectively quantify contamination of the signal. The present work describes a set of computer algorithms that automatically select EMGdi free of the electrocardiogram and numerically quantify the common artifacts that affect the EMGdi. The algorithms were tested 1) on human EMGdi (n = 5) obtained with esophageal electrodes positioned at the level of the gastroesophageal junction, 2) on EMGdi obtained in mongrel dogs (n = 5) with intramuscular electrodes in the costal diaphragm, and 3) on computer-simulated power spectra. For authentic and simulated power spectra, indexes were obtained by the algorithms and were able to quantify signal disturbances induced by noise, electrode motion, esophageal peristalsis (in humans), and non-QRS complex-related electrocardiogram activity. With the index inclusion thresholds set to levels that allowed for a high signal acceptance rate with relatively small artifact-induced fluctuations (10-15%) of the EMGdi center frequency, the computer algorithms were found to be as reliable as or more reliable than other methods, including careful visual selection of the time domain signals by experienced analysts. In conclusion, the frequency domain application of computer algorithms offers a reliable and reproducible means to objectively quantify the sources that contaminate the interference pattern EMG.

Contraction-dependent modulations in regional diaphragmatic blood flow.

Blood flow (Q) of the diaphragm was measured simultaneously with Doppler probes placed on diaphragmatic veins and an artery and by direct volumetric measurements obtained from cannulation of diaphragmatic blood vessels. The Doppler converting coefficients obtained were 6.27, 7.25, 4.21, and 41.07 ml.min-1.kHz-1 for left phrenic artery flow (Qpha), phrenic vein flow (Qphv), internal mammary vein flow (Qimv), and azygos vein flow (Qazv), respectively. The time course of Qpha, Qphv, Qimv, and Qazv after imposed patterns of diaphragmatic contraction was measured in nine anesthetized dogs. Each pattern consisted of various combinations of transdiaphragmatic pressure (Pdi), frequency of pacing (f), and duty cycle obtained by bilateral phrenic nerve stimulation. The dogs were prepared with chests open and loosely casted abdomens. Qpha, Qphv, Qimv, and Qazv were measured at rest (control, passive diaphragm, mechanical ventilation) and at two submaximal levels of stimulation (30 and 60% of Pdimax). The f was 10 or 30 cycles/min and the duty cycle was 0.25, 0.50, and 0.75. The results show 1) Qpha, Qphv, Qimv, and Qazv reached stable values (equilibration) after 30-36 s of pacing; 2) the steady Qpha, Qphv, and Qimv were linearly related to Pdi, and they were related by a parabolic function to duty cycle, whereas Qazv was not significantly affected by Pdi and increased linearly as a function of the duty cycle; 3) the diaphragmatic blood drainage was approximately 60% through the intercostal veins leading into the azygos trunk, 25% through the phrenic vein, and 15% through the internal mammary vein during pacing of the diaphragm at a duty cycle of 0.50 and 60% Pdimax; and 4) for a given pacing pattern, Qpha and Qphv increased with f, but Qimv and Qazv did not.

Costal and crural diaphragm in early inspiration: free breathing and occlusion.

Changes in length of costal and crural segments of the canine diaphragm were measured by sonomicrometry within the first 100-300 ms of inspiration during CO2 rebreathing in anesthetized animals. Both segments showed small but significant decreases in end-expiratory length during progressive hypercapnia. Although both costal and crural segments showed electromyographic activity within the first 100 ms of inspiration, in early inspiration crural shortening predominated with minimal costal shortening. Neither segment contracted isometrically early in inspiration in the presence of airway occlusion. The amount of crural shortening during airway occlusion exceeded costal shortening; both segments showed increased shortening with prolonged occlusion and increasing CO2. Costal and crural shortening at 100 ms was not different for unoccluded and occluded states. These observations suggest that neural control patterns evoke discrete and unequal contributions from the diaphragmatic segments at the beginning of an inspiration; the crural segment may be predominately recruited in early inspiration. Despite traditional assumptions about occlusion pressure measurement (P0.1), diaphragm segments do not contract isometrically during early inspiratory effort against an occluded airway.

Velocity of shortening of inspiratory muscles and inspiratory flow.

Respiratory muscle length was measured with sonomicrometry to determine the relation between inspiratory flow and velocity of shortening of the external intercostal and diaphragm. Electromyographic (EMG) activity and tidal shortening of the costal and crural segments of the diaphragm and of the external intercostal were recorded during hyperoxic CO2 rebreathing in 12 anesthetized dogs. We observed a linear increase of EMG activity and peak tidal shortening of costal and crural diaphragm with alveolar CO2 partial pressure. For the external intercostal, no consistent pattern was found either in EMG activity or in tidal shortening. Mean inspiratory flow was linearly related to mean velocity of shortening of costal and crural diaphragm, with no difference between the two segments. Considerable shortening occurred in costal and crural diaphragm during inspiratory efforts against occlusion. We conclude that the relation between mean inspiratory flow and mean velocity of shortening of costal and crural diaphragm is linear and can be altered by an inspiratory load. There does not appear to be a relationship between inspiratory flow and velocity of shortening of external intercostals.

Costal and crural diaphragm function during panting in awake canines.

During natural panting for thermal regulation, the pattern of activation of the major respiratory muscles, including costal and crural diaphragm segments, is not known. We measured diaphragm segmental length, shortening, and electromyographic (EMG) activity in five chronically implanted canines awake and breathing spontaneously at rest and during a mild dry heat stress. During panting, minute ventilation increased fourfold from 5.07 l/min and respiratory rate increased from 16.9 to 192.8 breaths/min or 3.2 Hz. During panting, end-expiratory length of both costal and crural segments decreased, concurrent with significant increases in end-expiratory EMG. With the onset of panting, tidal costal shortening decreased significantly from 6.29% of end-expiratory length to 3.54%, whereas crural shortening decreased from 6.04 to 2.46%. Meanwhile, segmental EMG tended to increase during panting. During panting, intrabreath costal and crural segmental function revealed differential activation; the costal segment shortened in concert with inspiratory flow, whereas peak crural shortening occurred in expiration, almost 180 degrees out of phase with costal. The divergence in segmental shortening during panting was accompanied by a lesser shift in timing of segmental EMG. In the awake spontaneously panting canine, asynchronous costal and crural shortening may enhance gas mixing in a manner analogous to high-frequency ventilation.

Costal and crural diaphragm function during CO2 rebreathing in awake dogs.

If costal and crural diaphragm segments can perform as separate muscles, then CO2-stimulated ventilation may elicit differential segmental function. We studied diaphragm segmental length, shortening, and electromyogram (EMG) activity in 10 awake dogs chronically implanted with sonomicrometer transducers and EMG electrodes. During CO2 rebreathing, segmental shortening and EMG activity per whole tidal breath progressively increased, but segmental responses could not be differentiated at any level of CO2. With increasing CO2, resting end-expiratory length of both diaphragm segments increased. During the complete intrabreath inspiratory-expiratory cycle, costal and crural diaphragm revealed distinctive segmental function. At rest, crural shortening exceeded costal shortening in earliest inspiration, costal and especially crural shortening persisted into early expiration, and EMG activity of the crural segment was greater than that of the costal segment in earliest inspiration and showed more end-inspiratory/early expiratory [post-inspiratory inspiratory activity (PIIA)] activity. During CO2-stimulated breathing, neither segment shortened during the inspiratory flow of earliest inspiration. During CO2 rebreathing, shortening of the crural segment exceeded that of the costal segment during early inspiration and outlasted costal shortening during expiration; for both segments, shortening persisted after termination of inspiratory airflow. With increased CO2, EMG activity of the crural segment preceded that of the costal segment in earliest inspiration and was dominant into expiration, whereas costal EMG activity terminated abruptly with inspiratory flow. Thus, costal EMG PIIA was not evident during hypercapnia, whereas crural EMG PIIA was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of costal and crural diaphragm during progressive hypoxia or hypercapnia.

Because costal and crural diaphragm segments have different functional characteristics, ventilatory stimulation with hypoxia or hypercapnia may elicit differential segmental function. We report measurements of diaphragm segmental length, shortening, and electromyogram (EMG) activity from 11 canines that were chronically implanted with sonomicrometry transducers and EMG electrodes and then studied a mean of 18 days postimplantation while awake and breathing spontaneously during CO2 rebreathing and progressive isocapnic hypoxia. Ventilatory responses to hypercapnia and progressive hypoxia were moderate at 1.13 +/- 0.31 (SD) 1. min-1. mm-1 arterial Pco2 and -0.98 +/- 0.51 l. min-1.%arterial O2 saturation-1. When tidal values for breathing pattern and segmental function were compared at matching tidal volumes that correspond to mean CO2 of 49.4 arterial Pco2 and 77% arterial O2 saturation, there was no significant difference in resting length, tidal shortening, or tidal EMG of costal or crural segments. Intrabreath profiles of flow, shortening, and EMG activity at matched tidal volumes showed that 1) inspiratory flow during hypoxia was significantly greater during early inspiration, 2) crural EMG activity preceded costal EMG activity in early inspiration during both hypercapnia and hypoxia, 3) both segments showed increased postinspiratory inspiratory activity with stimulated ventilation, and 4) postinspiratory shortening and EMG were greatest for the crural segment during hypoxia. These results suggest that costal and crural diaphragm segments exhibit differential function during chemical stimulation, especially during postinspiration.

Recovery of diaphragm function after laparotomy and chronic sonomicrometer implantation.

If sonomicrometry transducers could be implanted permanently into the diaphragm, direct measurements of costal and crural length and shortening could be made during recovery from the laparotomy and then indefinitely in an awake, non-anesthetized mammal. We report results from six canines in which we successfully implanted transducers onto the left hemidiaphragm through a midline laparotomy and measured segmental shortening and ventilation at intervals through 22 days of postoperative recovery. After laparotomy, breathing pattern, including tidal volume, respiratory rate and mean inspiratory flow, stabilized by the 4th postoperative day (POD). Tidal shortening of costal and crural segments increased from 1.82 and 1.45% of end-expiratory length (%LFRC) on the 2nd POD to 5.32 and 8.56% LFRC, respectively, after a mean of 22 POD. Segmental shortening did not stabilize until 10 POD, and the recovery process displayed a sequence of segmental motions: lengthening, biphasic inspiratory lengthening-shortening, and increasing simple shortening. Three weeks after implantation, costal and crural segments were stable and shortening 5.32 and 8.56% LFRC, respectively, and capable of shortening 49% LFRC with maximal phrenic stimulation. In a pair of recovered animals, the initial postoperative dysfunction did not recur after a subsequent, simple laparotomy. At postmortem examination, the chronically implanted sonomicrometer transducers were found to have evoked only a thin fibrotic capsule within the diaphragm.

Enhancement of signal quality in esophageal recordings of diaphragm EMG.

The crural diaphragm electromyogram (EMGdi) is recorded from a sheet of muscle, the fiber direction of which is mostly perpendicular to an esophageal bipolar electrode. The region from which the action potentials are elicited, the electrically active region of the diaphragm (EAR(di)) and the center of this region (EAR(di ctr)) may vary during voluntary contractions in terms of their position with respect to an esophageal electrode. Depending on the bipolar electrode's position with respect to the EAR(di ctr), the EMGdi is filtered to different degrees. The objectives of the present study were to reduce these filtering effects on the EMGdi by developing an analysis algorithm referred to as the "double-subtraction technique." The results showed that changes in the position of the EAR(di ctr) by +/- 5 mm with respect to the electrode pairs located 10 mm caudal and 10 mm cephalad provided a systematic variation in the EMG power spectrum center-frequency values by +/- 10%. The double-subtraction technique reduced the influence of movement of the EAR(di ctr) relative to the electrode array on EMG power spectrum center frequency and root mean square values, increased the signal-to-noise ratio by 2 dB, and increased the number of EMG samples that were accepted by the signal quality indexes by 50%.

Influence of tension time on muscle fiber sarcolemmal injury in rat diaphragm.

We hypothesized that the amount of sarcolemmal injury is directly related to the total tension time (TT(tot)), calculated as mean tension x total stimulation time. Diaphragm strips from Sprague-Dawley rats were superfused at optimal muscle length with Krebs containing procion orange to identify sarcolemmal injury. TT(tot) was induced by stimulation with 100 Hz for 3 min at duty cycles of 0.02, 0.15, 0.3, and 0.6, or with continuous contractions at 0.2, 0.4, 0.6, and 1.0 of maximal tension. A significant positive correlation between TT(tot) and the percentage of fibers with injured sarcolemma (r(2) = 0.63, P < 0.05) is seen. Stimulation (at 100 Hz, duty cycle = 1) resulted in fast fatigue with low injury, likely caused by altered membrane conductivity. Stimulations inducing the largest injury are those showing progressive force loss and high TT(tot), where injury may be due to activation of membrane degradative enzymes. The maximal tension measured at 20 min poststimulation was inversely related to the number of fibers injured, suggesting loss of force is caused by cellular injury.

Morphological and functional recovery from diaphragm injury: an in vivo rat diaphragm injury model.

Our objective was to develop an in vivo model to study the timing and mechanisms underlying diaphragm injury and repair. Diaphragm injury was induced in anesthetized rats by the application of a 100 mM caffeine solution for a 10-min period to the right abdominal diaphragm surface. Diaphragms were removed 1, 4, 6, 12, 24, 48, 72, and 96 h and 10 days after the injury, with contractile function being assessed in strips in vitro by force-frequency curves. The extent of caffeine-induced membrane injury was indicated by the percentage of fibers with a fluorescent cytoplasm revealed by inward leakage of the procion orange dye. One hour after caffeine exposure, 32.9 +/- 3.1 (SE) % of fibers showed membrane injury that resulted in 70% loss of muscle force. Within 72-96 h, the percentage of fluorescent cells decreased to control values. Muscle force, however, was still reduced by 30%. Complete muscle strength recovery was observed 10 days after the injury. Whereas diaphragmatic fiber repair occurred within 4 days after injury induction, force recovery took up to 10 days. We suggest that the caffeine-damaged rat diaphragm is a useful model to study the timing and mechanisms of muscle injury and repair.

Mechanisms of muscle fatigue.

The concept of muscle fatigue as a factor limiting muscle performance has evolved into one in which fatigue is avoided in order to protect the muscle from injury induced by over stimulation. No one mechanism accounts for all the changes in muscle performance occurring during fatigue. Research on pathophysiological factors limiting force production or shortening capacity during the fatigue process has widened to detailed electrophysiologic, metabolic and molecular aspects. All are extensively reviewed in the present paper. The known mechanisms are likely to be interdependent, synergistic, and integrated. A careful interpretation of individual research is implied, particularly when data from experimental animal models are translated to human beings.

Time-based gene expression programme following diaphragm injury in a rat model.

It was hypothesised that diaphragm injury activates a time-based programme of gene expression in muscle repair. Gene expression of different substances, such as proteases (calpain 94 (p94)), transcription factors (myogenin and cFos), growth factors (both basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-II), and structural proteins (myosin heavy chain (MHC) and titin), was quantified by RT-PCR in rat diaphragms exposed to caffeine-induced injury. Injured and noninjured (control) rat hemidiaphragms were excised at different time points (1-240 h). In injured hemidiaphragms, in comparison with control muscles, p94 expression levels peaked at 1 h post-injury (PI), cFos mRNA levels began to rise, after an initial dip, and peaked at 96 h PI, while myogenin mRNA levels started to increase as early as 12 h PI, IGF-II mRNA levels initially decreased until 48 h PI and increased thereafter, peaking at 72 h PI, bFGF mRNA levels rose to a maximum at 96 h PI, and MHC and titin mRNA levels were significantly elevated at 72 h PI. Caffeine-induced diaphragm injury is followed by a time-based expression programme of different genes tailored to meet muscle repair needs.

Load compensation in obese patients during quiet tidal breathing.

Seventeen eucapnic massively obese patients and eight normal subjects had their respiratory cycle parameters studied while breathing room air at rest. Despite large variations in the degree of obesity, our patients demonstrated normal mean inspiratory and expiratory flow rates, duty cycles, and minute ventilation. The maintenance of normal mean inspiratory flow rates was found to be dependent on an augmentation of neuromuscular drive (P0.1); furthermore, a strong positive correlation between percentage ideal body weight (i.e., the degree of obesity) and P0.1 was present. The obese were found to partition their tidal volume preferentially to their rib cage compartment, choosing to leave the abdominal compartment relatively immobile. Analysis of the diaphragmatic electromyogram revealed a persistence of activity into early expiration, the length of which also depended on the degree of obesity. These findings suggest that the diaphragm's volume-generating function in the obese is reduced, and furthermore the persistence of its activity in expiration serves to attenuate the rate of expiratory flow. No significant difference in any respiratory cycle parameter was found between simple obesity patients and formerly hypercapnic obese patients.

Chest wall distortion and regional lung volume distribution in erect humans.

Using 133Xe measured the regional distribution of FRC and of boluses administered at FRC in seated subjects during relaxation, lateral compression of the lower rib cage, and contraction of the inspiratory muscles so that mouth pressure was 50 cmH2O subatmospheric. Lateral compression increased apex-to-base differences of volume and bolus distribution, suggesting an increase of the apex-to-base gradient of pleural surface pressure. Changes in rib cage shape were measured with magnetometers and were qualitatively similar to those associated with increases in apex-to-base difference of pleural surface pressure in animals. Inspiratory effort decreased apex-to-base difference in volume and induced a similar trend in bolus distribution. Though changes in the rib cage shape were directionally similar, they were much smaller than those associated with decreased pleural surface pressure gradients in animals, and the changes in regional volume we observed were more likely due to forces generated by diaphragmatic contraction. These results were compatible with the apex-to-base gradient of pleural pressure being strongly influenced by shape adaptation between lung and chest wall.

The pattern of breathing in diffuse lung fibrosis.

The volume and time components of the breathing cycle together with the mouth occlusion pressure P0.1) were measured in 12 patients with chronic diffuse lung fibrosis (DLF) breathing air and in nine normal subjects matched for age and sex. In addition, static lung elastance was measured in all patients. It was found that in DLF the frequency of breathing (f) and P0.1 were positively correlated with lung elastance, whereas tidal volume (VT) decreased significantly with increasing elastance. Minute ventilation and mean inspiratory flow were independent of lung elastance. The VT and f of DLF reported in this paper and those from other published reports were compared with the VT and f of elastically loaded normal subjects. At equivalent levels of elastance, both DLF and loaded normal subjects show qualitatively similar changes. This data suggests that in DLF patients the inspiratory neuromuscular drive is increased as a function of their elastic load, the increase being sufficient to maintain alveolar ventilation within normal limits.