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Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity.

Breathing at very low lung volumes might be affected by decreased expiratory airflow and air trapping. Our purpose was to detect expiratory flow limitation (EFL) and, as a consequence, intrinsic positive end-expiratory pressure (PEEPi) in grossly obese subjects (OS). Eight OS with a mean body mass index (BMI) of 44 +/- 5 kg/m2 and six age-matched normal-weight control subjects (CS) were studied in different body positions. Negative expiratory pressure (NEP) was used to determine EFL. In contrast to CS, EFL was found in two of eight OS in the upright position and in seven of eight OS in the supine position. Dynamic PEEPi and mean transdiaphragmatic pressure (mean Pdi) were measured in all six CS and in six of eight OS. In OS, PEEPi increased from 0.14 +/- 0.06 (SD) kPa in the upright position to 0.41 +/- 0.11 kPa in the supine position (P < 0.05) and decreased to 0.20 +/- 0.08 kPa in the right lateral position (P < 0.05, compared with supine), whereas, in CS, PEEPi was significantly smaller (<0.05 kPa) in each position. In OS, mean Pdi in each position was significantly larger compared with CS. Mean Pdi increased from 1.02 +/- 0.32 kPa in the upright position to 1.26 +/- 0.17 kPa in the supine position (not significant) and decreased to 1. 06 +/- 0.26 kPa in the right lateral position (P < 0.05, compared with supine), whereas there were no significant changes in CS. We conclude that in OS 1) tidal breathing can be affected by EFL and PEEPi; 2) EFL and PEEPi are promoted by the supine posture; and 3) the increased diaphragmatic load in the supine position is, in part, related to PEEPi.

Adult↗

Dyspnea and diaphragmatic fatigue in patients with chronic obstructive pulmonary disease. Responses to theophylline.

This study sought answers to 2 questions: (1) Is severe dyspnea to the point of exhaustion regularly accompanied by diaphragmatic fatigue in patients with moderately severe chronic obstructive pulmonary disease (COPD)? (2) When diaphragmatic fatigue occurs in such patients, does theophylline prevent or delay its onset? Eight eucapnic patients with moderately severe COPD were subjected to 2 different stresses to the point of severe dyspnea requiring cessation of the stress. The stresses were cycle exercise and inspiratory resistive breathing, the latter requiring a tidal Pdi equal to 60% of Pdimax. Despite incapacitating dyspnea, objective evidence of diaphragmatic fatigue was not encountered during cycle exercise. During inspiratory resistive breathing, diaphragmatic fatigue was encountered in all patients as defined by consistent inability to attain a target Pdi during final moments of the resistance run. Patients were uniformly extremely dyspneic at this point. In neither stressful maneuver did oral sustained-release theophylline show a convincing or significant advantage over placebo when administered in a randomized double-blind crossover protocol. These results suggest that the diaphragmatic fatigue encountered in this sort of COPD patient may be of predominantly central rather than peripheral (myogenic) origin and that theophylline may not be effective in this type of fatigue.

Diaphragm↗

Nursing perspectives in the management of infants and children requiring thoracic surgery.

Nurses who care for infants and children undergoing thoracic surgery must function and make decisions which take into account a multiplicity of complex data. This necessitates a background of knowledge, skill and intuition which guides their nursing practice. The principles of holistic care in which the total needs of the infant and child are met within the context of the family are seen as an important approach to patient care. Selected perspectives in the care of infants with congenital and acquired thoracic anomalies are discussed, in particular infants with congenital diaphragmatic hernia and oesophageal atresia. The preparation of children for chest surgery and the postoperative nursing management are outlined and include aspects of pain management, physiotherapy and chest drain care.

Chest Tubes↗

Intercellular adhesion molecule (ICAM-1) response after major neonatal surgery.

Surgical stress induces systemic endocrine-metabolic responses that influence the function of endothelial cells (EC) to cause various systemic reactions. Intercellular adhesion molecule (ICAM)-1 is an adhesion molecule that plays an important role in inflammation, and increased expression of ICAM-1 on EC is a reflection of EC activation. In this study, we investigated the ICAM-1 response to surgical stress in neonates undergoing major surgery. Fifteen neonates (mean age at surgery: 3.5 +/- 1.2 days) were divided into two groups according to indications for surgery: Group I: Congenital diaphragmatic hernia without persistent pulmonary hypertension (n = 5); Group II: Gastrointestinal surgery [n = 10: duodenal atresia (n = 3), intestinal atresia (n = 6), and esophageal atresia (n = 1)]. Serum samples were obtained preoperatively, immediately after completion of surgery (time zero), and 24, 48, 72, 96, and 120 h after surgery to measure ICAM-1 levels using an enzyme-linked immunosorbent assay, C-reactive protein (CRP), and white blood cell count (WBC). Postoperative recovery was uneventful in all cases. ICAM-1 levels in both groups increased significantly within 24 h of surgery (Group I: P = 0.0038, Group II: P = 0.0320). In Group I, ICAM-1 peaked 72 h postoperatively while in Group II it continued to rise until 96 h postoperatively. The difference between peak levels reached was not significant. CRP was first detected 24 h postoperatively in both groups and continued to increase until 48 h postoperatively. Again, the difference between peak levels reached was not significant. No significant changes in WBC were observed in either group. We found that ICAM-1 increases in response to surgical stress in neonates, although there was no significant difference in levels. However, surgical stress as represented by serum ICAM-1 would appear to last longer with intestinal surgery than with non-intestinal surgery. Further research is required to establish the usefulness of ICAM-1 as an easily detectable substance associated with endothelial damage that reflects the host's response to major surgical stress.

Biomarkers↗

Theoretical analysis of chest wall mechanics.

A mathematical model of the chest wall partitioned into rib cage, diaphragmatic and abdominal components is developed consistent with published experimental observations. The model describes not only the orthodox chest wall movements (rib cage and abdomen expand together during inspiration) of the quietly breathing standing adult, but also Mueller maneuvers (inspiration against an occluded airway opening) and the paradoxical breathing patterns (rib cage contracts while abdomen expands during inspiration) observed in quadriplegia and in the newborn. The abdomen is inferred to act as a cylinder reinforced by the abdominal muscles functioning similarly to bands around a barrel. The rib cage and abdominal wall are inferred to act not as though they were directly attached to one another, but as though they were being pressed together by the skeleton. Furthermore, transabdominal pressure is visualized as acting, not across the rib cage isolated from the diaphragm, as has been suggested previously, but instead, across the combined rib cage and diaphragm acting as a deformable unit containing the lungs.

Abdomen↗

Interaction between upper airway negative pressure pulses and CO2 on breathing pattern.

The interaction between CO2 and negative pressure pulses on breathing pattern was investigated in 10 anesthetized, spontaneously breathing rabbits. The upper airway was functionally isolated into a closed system. A servo-respirator triggered by the inspiratory activity of the diaphragm was used to apply pressure pulses of -15 cmH2O to the isolated upper airway in early inspiration while the animal was breathing room air, 100% O2, 6% CO2 in O2, or 9% CO2 in O2. The negative pressure pulses produced a reversible inhibition of inspiration in most trials with resultant increase in inspiratory duration (TI); no change was observed in peak diaphragmatic electromyogram (Dia EMG) or expiratory duration, whereas a decrease was seen in mean inspiratory drive (peak Dia EMG/TI). This prolongation of inspiratory duration and decrease in mean inspiratory drive with negative pressure pulses persisted at higher levels of CO2; the slopes of the test breaths were not significantly different from that of control breaths. These results suggest that upper airway negative pressure pulses are equally effective in altering the breathing pattern at all levels of CO2.

Animals↗

[Picking up and analysis of the surface myoelectric signals of respiratory muscule].

In this paper, we introduce the technique used to obtain the surface diaphragmatic EMG and monitor respiratory activity. The signals are picked up from the ECG electrodes. By using an ECG masking system based on a digital processor, the dominant effect of the ECG (that is R-wave, P-wave and T-wave) was removed. Initial clinical measurements indicate this EMG method is more direct and effective than others for monitoring respiratory activity. It is hoped that this method can be used to monitor the development of respiratory function.

Analog-Digital Conversion↗

Small intestinal physiology and pathophysiology.

The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents to uniformly and evenly expose them to the mucosal surface, and to propel them distally at a rate that allows optimal absorption of food components, and reabsorption of bile. Most of these functions are performed by individual phasic contractions. In humans, the phasic contractions are largely disorganized in time and space. These contractions may cause mixing and agitation of luminal contents with slow distal propulsion. Occasionally, an individual contraction of large amplitude and long duration migrates over several centimeters and may rapidly propel the contents over this distance. In general, the spatial and temporal relationships of individual phasic contractions become less organized distally, resulting in a slower propulsion rate in the distal small intestine than in the proximal small intestine. The migrating clustered contractions generated after a meal may also be propulsive, but because of their unpredictable and irregular occurrence, their precise role in postprandial propulsion is incompletely understood. Rapidly migrating contractions may occur when the electrical control activity is obliterated by pharmacologic agents or during parasitic infections. Their effects on motility are not known yet. Between meals, when digestion is complete, the small intestine generates migrating motor complexes that help keep the small intestine clean by dislodging debris from the villi and dumping them into the colon. This may prevent decay of these materials in the small intestine and limit their contribution to bacterial overgrowth. Giant migrating contractions may perform a similar function in the distal small intestine as well as return any refluxed fecal material back to the colon. However, the major role of giant migrating contractions may be, in pathologic states, associated with abdominal cramping and diarrhea. Giant migrating contractions are associated with mass movements. Vomiting is preceded by a retrograde giant contraction. This contraction rapidly empties the contents of the proximal half of small intestine into the stomach in preparation for vomitus expulsion by contraction of abdominal and diaphragmatic muscles. The three basic mechanisms of control of spatial and temporal patterns of contractions are myogenic, neural, and chemical.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Correction of congenital diaphragmatic hernia in utero, V. Initial clinical experience.

Review of our experience with 45 cases of prenatally diagnosed congenital diaphragmatic hernia (CDH) confirms that most fetuses (77%) will not survive despite optimal pre- and postnatal care. Polyhydramnios, associated anomalies, early diagnosis, and a large volume of herniated viscera (including liver) are associated with a particularly dismal prognosis. After extensive experimental work demonstrated the efficacy, feasibility, and safety of repair in utero, we attempted to salvage six highly selected fetuses with severe CDH by open fetal surgery. Five had liver incarcerated in the chest: three died at operation because attempts to reduce the liver compromised umbilical venous return. In one, a Goretex diaphragm was constructed around the liver, but the baby died after birth. The last two fetuses, one with incarcerated liver, were successfully repaired. Both demonstrated rapid growth of the lung in utero, had surprisingly good lung function after birth despite prematurity, had the abdominal patch removed at 2 weeks, and subsequently died of nonpulmonary problems (an unrelated nursery accident in one and intestinal complications in the other). The only maternal complication was amniotic fluid leak and preterm labor. All six women are well and four have had subsequent normal children. From this phase I experience, we conclude that fetal surgery appears safe for the mother and her reproductive potential, that fetal CDH repair is feasible in selected cases, and that the fetal lung responds quickly after decompression. However, fetal repair remains a formidable technical challenge.

Adolescent↗

Diaphragmatic activity induced by cortical stimulation: surface versus esophageal electrodes.

Evoked responses of the diaphragm can be induced by magnetic cortical stimulation and recorded by either surface or esophageal electrodes. The former recording system is tolerated better by the patient but has potential problems with the specificity of the diaphragmatic signal. This study compares the responses of the diaphragm to cortical stimulation that were recorded simultaneously with surface and esophageal electrodes on seven patients (61 +/- 4 yr) with chronic obstructive pulmonary diseases. Stimuli were delivered in three ventilatory conditions: at baseline, during deep breathing, and during voluntary panting. No differences were observed between results recorded by surface and esophageal electrodes [amplitude of the compound motor of the action potential (CMAP), 0.8 +/- 0.1 vs. 0.8 +/- 0.1 mV, NS; latency, 13.1 +/- 0.4 vs. 12.6 +/- 0.5 ms, NS]. In addition, significant correlations were found (CMAP, r = 0.77, P < 0.001; latency, r = 0.71, P = 0.002). The concordance analysis, however, indicated some dissimilarity between the recordings of the electrodes (CMAP, R1 = 0.31; latency, R1 = 0.26). These differences may be due to the area of the muscle mainly recorded by each electrode and/or to the additional activity from other muscles recorded by surface electrodes. On the other hand, the diaphragmatic responses observed in these patients with chronic obstructive pulmonary diseases were similar to those previously reported in healthy subjects.

Action Potentials↗

Sleep apnea syndrome. Can it induce hemodynamic changes?

Of 250 patients referred to the Stanford Sleep Disorders Clinic, 35 were diagnosed for a sleep induced apnea syndrome. Thirty of them (27 adults and 3 children) were nonobese and complained of a sleep disorder. In 12 patients (9 adults and 3 children) extensive cardiorespiratory workups were done during sleep and wakefulness. Three types of sleep induced apnea syndrome were identified: diaphragmatic (or central), obstructive and mixed. The diaphragmatic type was predominant in sleep apnea insomnia; obstructive was predominant in sleep apnea hypersomnia. Hemodynamic changes were documented during sleep. Tracheostomy, done in two cases, improved the sleep induced symptomatology.

Adult↗

Effect of acute starvation on rat diaphragm function.

The effects of 130 h of acute starvation on diaphragm contractility fatigue were studied in isolated rat diaphragm strip preparations with phrenic nerve stimulation. Compared with controls, starvation produced a reduction in body and diaphragm weights. Twitch and tetanic tensions were reduced by starvation; however, when the force was calculated as the strength (normalized for the weight or muscle cross-section area of the diaphragm), no difference was observed between the control and experimental groups. Starvation induced a significant downward shift in the force-frequency relationship, and also increased diaphragm fatigability, but it had no effect on twitch contraction and relaxation time. We conclude that 130 h of acute starvation decreases diaphragmatic force and endurance, but the strength does not change, because of the reducing diaphragmatic mass.

Animals↗

Distribution and location of slowly adapting pulmonary stretch receptors in the airways of cats.

The distribution and location of slowly adapting pulmonary stretch receptors (PSRs) that affect respiratory and cardiovascular functions were investigated in anaesthetized, artificially ventilated and thoracotomized cats. The location of the receptors was done by punctate stimulation and local mechanical stimulation after occlusion of the trachea at end-expiration (Exp). 84% of the slowly adapting PSRs were found to be located in the lung parenchyma. The occlusion technique alone was found to be of help only for a limited population of stretch receptors. The intrapulmonary distribution of PSRs revealed a greater percentage of receptors in the diaphragmatic lobe. No correlation was found between conduction velocity and receptor location. Both the slowly and rapidly conducting receptors were found to be scattered throughout the entire lung parenchyma. However, it was observed that while the majority of low threshold (LT) PSRs were located closer to the hilum of the lung, many of the higher threshold (HT) receptors were located farther away. In addition, when veratrine was administered into the pulmonary circulation, 83% of HT PSRs studied were stimulated by the drug, while only 25% of LT PSRs under study could be stimulated this way. The significance of the above findings is discussed.

Adaptation, Physiological↗

Excitatory cardiovascular and respiratory effects of baclofen in intact rats.

The rat has become the preferred animal model for study of the central control of the cardiorespiratory system. However, data in the literature suggest that the role of GABAB receptors in control of the respiratory timing may be different in rats from that in other species. Therefore in this study we investigated cardiorespiratory effects of repeated injections of 0.5 nM baclofen and 50 nM CGP35348, GABAB receptor agonist and antagonist, respectively, applied into the fourth ventricle of urethane-anesthetized intact, spontaneously breathing Wistar rats. Baclofen increased arterial blood pressure (ABP), heart rate, inspiratory time (Ti), and the rate of rise (Di/t) and peak amplitude of the integrated diaphragmatic EMG (Di). Expiration (Te) was unaffected. CGP35348 reversed the ABP and Di effects of baclofen and decreased Di/t and Te below their control values, whereas Ti remained prolonged. These excitatory effects of baclofen are consistent with previously reported effects of low i.v. doses of baclofen in cats, and suggest that GABAB receptors may modulate the depth and duration of inspiration. We conclude that the intact rat represents a suitable animal model for investigations of the integrated control of cardiorespiratory functions. To our knowledge this is the first investigation reporting excitatory effects of GABAB receptor stimulation on inspiratory activity in rats. The depressant effects of baclofen on the respiratory rhythm reported in the rat "isolated" brain in situ, and the neonatal rat brainstem--spinal cord in vitro seem to be unique for those specific preparations.

Animals↗

Human diaphragm remodeling associated with chronic obstructive pulmonary disease: clinical implications.

Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.

Adaptation, Physiological↗

Pulmonary elastic fibers in normal human development and in pathological conditions.

Normal human pulmonary elastic fiber development and development in some pathological conditions were examined using elastic stains by light microscopy, electron microscopy, and immunohistochemistry. In normal development elastic fibers, composed mainly of microfibrils, first appeared around primitive bronchioles at 10 weeks of gestation. As they matured, their appearance became more amorphous, and they extended into the peripheral alveolar walls. Development of elastic fibers was retarded in the hypoplastic lungs of the oligohydramnios syndrome, diaphragmatic hernia, and hydrops fetalis. Elastic development was also retarded in congenital pulmonary lymphangiectasia and in focal areas of lungs with pulmonary dysplasia. Distribution of well-developed elastic fibers was found around the dilated bronchioles and alveoli in cases of congenital cystic adenomatoid malformation and extralobar pulmonary sequestration. Elastic fibers were distributed irregularly and unevenly in the lungs of bronchopulmonary dysplasia and ventilated cases of Wilson Mikity syndrome. In addition, four very immature infants who had progressively deteriorating respiratory function showed an almost total lack of elastic fibers in their alveolar walls.

Chronic Disease↗

Optimal level of pressure support ventilation for recovery from diaphragmatic fatigue in rabbits.

OBJECTIVE: To determine whether there is an optimal level of pressure support ventilation (PSV) for recovery from acute diaphragmatic fatigue. DESIGN: Prospective laboratory trial. SETTING: Experimental laboratory. SUBJECTS: Twenty healthy adult New Zealand White rabbits. INTERVENTIONS: Diaphragmatic fatigue was induced with 50 Hz of phrenic nerve stimulation for 30 mins. Recovery was compared between inspiratory load + PSV of 0 cm H2O (L0), inspiratory load + PSV of 60 cm H2O (L60), inspiratory load + PSV of 80 cm H2O (L80), and PSV of 0 cm H2O without inspiratory load (SB) for 90 mins immediately after the end of the fatigue-inducing procedure. To add inspiratory load during the recovery phase, three pressure threshold valves, each having an opening pressure of -20 cm H2O, were used. MEASUREMENTS AND MAIN RESULTS: After the fatigue-inducing procedure, diaphragmatic electromyogram and transdiaphragmatic pressure remained at baseline in both SB and L60, decreased in L80, and increased in L0. Recovery was assessed by abdominal cavity pressure (Pabd) generated by high-frequency (100 Hz) and low-frequency (20 Hz) stimulation. Pabd at 100 Hz recovered to baseline in L60 and SB but not in L0 and L80 (69.1%, 81.3%, 100.3%, and 100.7% of the baseline at 90 mins for L0, L80, L60, and SB, respectively). Pabd at 20 Hz did not differ among ventilatory settings. CONCLUSION: There is an optimal range of PSV assist level to improve recovery from diaphragmatic fatigue. Recovery was hampered not only by inadequate PSV but also by excessive PSV.

Airway Resistance↗