Effects of fatigue on the length-tetanic force relationship of the rat diaphragm.

It has been established that the in vivo operating length of the diaphragm corresponds to a wide range of the ascending limb of its length-tetanic force relationship. To investigate the length-dependent effects of fatigue on maximum force production, we constructed length-tetanic force relationships of rat costal diaphragm strips in vitro before and after fatigue induced by repetitive supramaximal electrical field stimulations at optimal length. Two levels of fatigue were studied (i.e., force reductions of 40 and 65% at optimal length). Results indicate that fatigue, when evaluated with high-frequency stimulations, causes a proportionately larger decrease in tetanic force at short muscle lengths as seen by a smaller control force-to-fatigue force ratio and an apparent shift in the length at which active force is zero. A possible explanation for the results obtained is failure of propagation of membrane depolarization into the t-tubule system at short muscle lengths, which is aggravated by fatigue evaluated by high-frequency stimulation.

Influence of global inspiratory muscle fatigue on breathing during exercise.

We evaluated the effect of global inspiratory muscle fatigue (GF) on respiratory muscle control during exercise at 30, 60, and 90% of maximal power output in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. Esophageal and gastric pressures, anteroposterior displacement of the rib cage and abdomen, breathing pattern, and perceived breathlessness were measured. Induction of GF had no effect on the ventilatory parameters during mild and moderate exercise. It altered, however, ventilatory response to heavy exercise by increasing breathing frequency and minute ventilation, with minor changes in tidal volume. This was accompanied by an increase in perceived breathlessness. GF significantly increased both the tonic and phasic activities of abdominal muscles that allowed 1) the diaphragm to maintain its function while developing less pressure, 2) the same tidal volume with lesser shortening of the rib cage inspiratory muscles, and 3) relaxation of the abdominal muscles to contribute to lung inflation. The increased work performed by the abdominal muscles may, however, lead to a reduction in their strength. GF may impair exercise performance in some healthy subjects that is probably not related to excessive breathlessness or other ventilatory factors. We conclude that the respiratory system is remarkably adaptable in maintaining ventilation during exercise even with impaired inspiratory muscle contractility.

Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2.

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.

Three-dimensional reconstruction of the in vivo human diaphragm shape at different lung volumes.

The ability of the diaphragm to generate pressures at different lung volumes (VLs) in humans may be determined by the following factors: 1) its in vivo three-dimensional shape, radius of curvature, and tension according to Laplace law; 2) the relative degree to which it is apposed to the rib cage (i.e., zone of apposition) and lungs (i.e., diaphragm dome); and 3) its length-force properties. To gain more insight into these factors we have reconstructed from nuclear magnetic images the three-dimensional shape of the diaphragm of four normal subjects under supine relaxed conditions at four different VLs: residual volume, functional residual capacity, functional residual capacity plus one-half of the inspiratory capacity, and total lung capacity. Under our experimental conditions the shape of the diaphragm changes substantially in the anteroposterior plane but not in the coronal one. Multivariate regression analysis indicates that the zone of apposition is dependent on both diaphragm shortening and lower rib cage widening with lung inflation, although much more on the first of these two factors. Because of the changes in anteroposterior shape and expansion of the insertional origin at the costal margin with lung inflation, the data therefore suggest that the diaphragm may be more accurately modeled by a "widening piston" (Petroll's model) than a simple "piston in a cylinder" model. A significant portion of the muscular surface is lung apposed, suggesting that diaphragmatic force has radial vectors in the dome and vectors along the body axis in the zone of apposition. The muscular surface area of the diaphragm decreased linearly by approximately 41% with VL from residual volume to total lung capacity. Diaphragmatic fibers may shorten under physiological conditions more than any other skeletal muscle. The large changes in fiber length combined with limited shape changes with lung inflation suggest that the length-twitch force properties of the diaphragm may be the most important factor for the pressure-generating function of this respiratory muscle in response to bilateral phrenic shocks at different VLs.

Effect of fatigue on diaphragmatic function at different lung volumes.

The transdiaphragmatic pressure twitches (PdiT) in response to single maximal shocks delivered bilaterally to the phrenic nerves were recorded as a function of lung volume when the diaphragm was fresh and when fatigued. All relationships were linear and negatively sloped (all r greater than 0.85). From these relationships PdiT was found to decrease with fatigue more rapidly and to recover more quickly at high than at low lung volumes. Complete recovery of PdiT at all lung volumes was greater than 1 h. Contraction and relaxation rate constants of PdiT did not change significantly with fatigue. We conclude that fatigue affects diaphragm contractility more at high than at low lung volumes and that changes in diaphragm contractility are best reflected in the measurement of PdiT as a function of lung volume.

[Evaluation of ultrasonography in the diagnosis of cirrhosis. Retrospective studies of 100 consecutive tests]. / Evaluation de l'ultrasonographie dans le diagnostic des cirrhoses. Etude rétrospective de 100 examens consécutifs.

This study was carried out in order to assess the value of ultrasonography in the diagnosis of cirrhosis. One hundred patients were studied within 2 weeks of the histological diagnosis of the liver disease (cirrhosis 49, acute or chronic hepatitis: 23, fatty liver: 16, normal liver: 12). Ultrasonic patterns were classified by a second examiner according to 5 hepatic criteria (volume, outline, echogenicity, attenuation of the ultrasound beam, enlargement of caudate lobe) and 3 extrahepatic criteria (dilatation of the portal vein, ascites, splenomegaly), leading to a ultrasonic diagnosis. Cirrhosis was diagnosed in 36 out of 49 patients (73 p. 100) by the echographist whereas clinical and biological data lead to diagnosis in only 27 out of these 49 patients (P = 0.057). Hepatocellular carcinoma was diagnosed only in 2 out of 5 patients. Splenomegaly (0.60) and caudate lobe enlargement (0.59) were the signs whose predictive value was the best for this group of patients. The ratio thickness of caudate lobe/global hepatic thickness (as measured on a sagittal cut through the inferior vena cava) allowed for easy assessment of caudate lobe size. The mean value of this ratio was significantly different (P less than 0.001) in the cirrhotic group (0.38 +/- 0.07) when compared to the non-cirrhotic one (0.28 +/- 0.06). Ratios greater than 0.35 were not seen in subjects with normal livers, nor were ratios greater than 0.40 seen in non-cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Function of the diaphragm during exercise]. / Czynnosc przepony podczas wysilku.

We examined the control of respiratory muscles with emphasis on the diaphragm during exercise at 30%, 60% and 90% of maximal working capacity in normal subjects. Control of the diaphragm was quantified by plotting transdiaphragmatic pressure (Pdi), its electromyographic activity (Edi) and its power (Wdi = Pdi x Dab/Ti) vs. workload and Pdi, an index of shortening velocity of diaphragmatic fibres (Dab/Ti) and Wdi vs. Edi. We observed that increase in Pdi (approximately 2-fold) from rest to heavy exercise was inadequately small comparing to increases in minute ventilation (approximately 9-fold) and Edi (approximately 4.5-fold). We hypothesized and confirmed that Wdi might increase even though Pdi decreased due to increasing Dab/Ti and expresses more closely diaphragmatic contribution to inspiratory effort during exercise than Pdi. Significantly augmented shortening velocity of the diaphragm suggests that it acts predominantly as a flow generator during exercise. It is strongly assisted in this task by abdominal muscles. The responsibility for generating inspiratory pressures falls on the inspiratory rib cage muscles. This arrangement may however impair diaphragm's performance even in healthy subjects as indicated by reduced Pdi twitch after exercise.

[Effect of respiratory muscle fatigue on their function during exercise]. / Wplyw zmeczenia miesni oddechowych na ich czynnosc podczas wysilku.

We evaluated the effect of global inspiratory muscle fatigue (GF) on respiratory muscle control during exercise at 30%, 60%, and 90% of maximal power output in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. Respiratory pressures, breathing pattern, and perceived breathlessness were measured. Induction of GF had no effect on the ventilatory parameters during mild and moderate exercise. It altered, however, ventilatory response to heavy exercise by increasing breathing frequency and minute ventilation, with minor changes in tidal volume. This was accompanied by an increase in perceived breathlessness. GF significantly increased both the tonic and phasic activities of abdominal muscles that allowed 1) the diaphragm to maintain its function while developing less pressure, 2) the same tidal volume with lesser shortening of the rib cage inspiratory muscles, and 3) relaxation of the abdominal muscles to contribute to lung inflation. The increased work performed by the abdominal muscles may, however, lead to a reduction in their strength. GF may impair exercise performance in some healthy subjects that is probably not related to excessive breathlessness or other ventilatory factors. The respiratory system is remarkably adaptable in maintaining ventilation during exercise even with impaired inspiratory muscle contractility.

[Indications of enteral nutrition in pancreatic disorders]. / Indications de la nutrition entérale dans les affections pancréatiques.

In the treatment of disorders of the pancreas, artificial nutrition must satisfy nutritional requirements while avoiding stimulation of exocrine pancreatic juice observed during oral feeding. Although total parenteral nutrition (PN) induces pancreatic hyposecretion or weak pancreatic stimulation, enteral nutrition (EN) whether elementary or semi-elementary type stimulates pancreatic secretion and the release of CCK, with weaker stimulation in case of intrajejunal feeding. In acute pancreatitis, semi-elemental EN by jejunal feeding has successfully been used in the treatment of moderately serious cases, once the acute phase of the disease has been passed. Although PN remains the best indication for the treatment of pancreatic fistula, several studies have reported the closure of pancreatic fistulas during elementary enteral feeding administered by jejunal route. In the treatment of chronic pancreatitis, EN especially provides nutritional support for very undernourished patients, most often in the preoperative context. Finally, in children suffering from cystic fibrosis of the pancreas, prolonged sessions of EN provide marked improvement in the nutritional and respiratory status of these patients.

Force-frequency relationships of in vivo human and in vitro rat diaphragm using paired stimuli.

Supramaximal stimuli, with time intervals of 100 ms (10 Hz) to 10 ms (100 Hz), were delivered in pairs to the phrenic nerves, bilaterally, in five seated normal subjects, while transdiaphragmatic pressure swings (Pdi,s) were recorded at relaxed end-expiratory lung volume with airways closed. In fresh diaphragms, Pdi,s increased between 10-20 Hz and reached a plateau between 20-30 Hz. Diaphragmatic fatigue decreased Pdi,s at all frequencies. Pdi,s was assumed to be the sum of two successive responses (T1+T2), T1 being constant at any frequency and equal to a single twitch, T2 being obtained by subtraction. We found that T2 amplitude, which was significantly reduced after fatigue, was fully returned to normal after 15 min rest at high, not at low, stimulation frequencies. The ratio of T2 at 10 Hz over 100 Hz (T2(10/100)) thus decreased from 1.33 +/- 0.05 before fatigue to 0.97 +/- 0.12 after fatigue, and to 0.81 +/- 0.06 after 15 min rest. Similar results were obtained in isolated rat diaphragmatic strips stimulated and fatigued in vitro, from which we found a highly linear relationship (r = 0.94, p < 0.001) between the ratio of T2(10/100) and that of tetanic force at 10 Hz over 100 Hz (P10/100). We conclude that phrenic nerve paired twitches provide similar information when obtained from phrenic tetanic stimulation in terms of diaphragmatic contractility, and the decrease in T2(10/100) ratio indicates diaphragm low frequency fatigue.

Assessment of diaphragm function using mouth pressure twitches in chronic obstructive pulmonary disease patients.

The relative invasiveness of the balloon catheter technique in measuring twitch transdiaphragmatic pressure (Pdit) limits its clinical use. By phrenic stimulation we obtained swings in mouth pressure (Pmt) in six COPD patients (age 50 to 72, FEV1 18 to 48% of predicted) at relaxed FRC (rFRC) and during graded inspiratory efforts (IE; twitch occlusion, TO). At rFRC, Pmt was damped and time lagged relative to the esophageal pressure twitch (Pes(t)), as if pressure had equilibrated through an RC system. Pmt was not correlated with Pdit. Conversely, Pmt and Pes(t) were always well matched during IE [Pmt = 0.971 (SEM +/- 0.028) Pes(t), r > 0.89], possibly in relation to a decrease in upper airway compliance or more uniform pleural pressure swings. Pmt decreased with the level of voluntary diaphragmatic contraction (Pdivol) in proportion to Pdit, reflecting a progressive increase in the level of diaphragm activation. During IE, Pmt was closely related to the voluntary mouth pressure in five subjects but not in the remaining subject, indicating intersubject variability in the level of diaphragmatic recruitment relative to other inspiratory muscles. We submit that measuring Pm during inspiratory efforts upon which bilateral phrenic stimulation is superimposed offers a relatively simple method for the assessment of diaphragm activation, potentially applicable in the clinical field.

Contractile properties of the human diaphragm during chronic hyperinflation.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS: In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS: At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS: The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.

Effects of fatigue, fiber length, and aminophylline on human diaphragm contractility.

The clinical relevance of methylxanthines as therapeutic agents for improving diaphragmatic contractility is controversial. In a double-blind, placebo-controlled trial, we investigated the effect of aminophylline on the contractility of fresh and fatigued human diaphragm at different lung volumes, and therefore as a function of fiber length. The diaphragmatic contractility of normal subjects was assessed by measurements of transdiaphragmatic pressure changes (Pdi,T) in response to single, bilateral, supramaximal phrenic-nerve shocks during relaxation from total lung capacity (TLC) to functional residual capacity (FRC). Fatigue was induced by resistive breathing. Therapeutic levels of theophylline were reached in all subjects. Under fresh (i.e., nonfatigue) conditions, aminophylline significantly increased Pdi,T at lung volumes above 75% of the inspiratory capacity (IC). Fatigue in the absence of aminophylline caused a disproportionately greater reduction of Pdi,T at high than at low lung volume (J. Appl. Physiol. 1992; 72:1064), which was rapidly reversible with rest. With aminophylline, the disproportionate decrease in diaphragmatic contractility at short fiber lengths was not observed. Aminophylline potentiates diaphragmatic contractility to a proportionately greater extent at short than at long fiber lengths, under both fresh and fatigued conditions. We explain these findings by known effects of muscle shortening, fatigue, and methylxanthines on excitation-contraction coupling mechanisms.