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Biocompatibility of peritoneal dialysis fluids: long-term exposure of nonuremic rats.

OBJECTIVES: Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model. METHODS: Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 microm), vascular density, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) beta1 mRNA expression were determined. Submesothelial collagen concentration was estimated by van Gieson staining. RESULTS: Submesothelial tissue thickness and vascular density, mediated by VEGF and TGFbeta production, in the diaphragmatic peritoneum increased significantly in rats exposed to any PD fluid. Gambrosol induced a marked increased fibrosis of the hepatic peritoneum. A significant increase in high mesothelial cells was observed in the Gambrosol group only. Net ultrafiltration was reduced in the Gambrosol and in the glucose-free groups compared to untreated controls. Small solute transport was unchanged, but all groups exposed to fluids showed significantly increased lymph flow. CONCLUSIONS: Our results show that long-term exposure to different components of PD fluids leads to mesothelial cell damage, submesothelial fibrosis, and neoangiogenesis. Mesothelial cell damage could be connected to the presence of GDP; the other changes were similar for all fluids. Peritoneal transport characteristics did not change in any consistent way and the neoangiogenesis observed was not paralleled by increased solute transport.

Animals↗

Comparison of segmental and global ejection fraction in ischaemic heart disease.

In order to evaluate whether segmental ejection fraction (SEF) is a better index of left ventricular (LV) performance than global ejection fraction (EF), 25 patients with significant coronary stenosis and normal EF were studied. SEF was estimated from the LV cineangiogram after dividing the LV into eight segments by means of a long axis and three equally spaced chords perpendicular to it. The area of a given segment was measured in the end-diastole and the end-systole and SEF was calculated by determining the percent decrease in area for each segment. 12 out of the 25 patients presented hypokinesis, akinesis or dyskinesis of at least two segments; the inferior apical and both diaphragmatic segments were the regions most frequently affected. In 7 patients, these abnormalities were compensated by hyperkinesis of two or three other segments, whereas in the remaining 5 patients contraction abnormalities were not accompanied by hyperkinesis in spite of a normal EF. It is concluded that SEF is a more sensitive index of regional LV function than EF in patients with ischaemic heart disease.

Coronary Disease↗

[Volume reduction surgery in emphysema].

Volume reduction surgery (VRS) is a new procedure based on the concept that relieving hyperinflation in emphysema improves diaphragmatic and chest wall mechanics and ventilation perfusion mismatch. We present our early experience with 16 patients who underwent VRS from August 1995 to June 1996. Patient selection was based on: PFT, CT scan, V/Q scan, ABG's and 6-min walk. After pulmonary rehabilitation, operation was by median sternotomy and bilateral lung shaving. Pulmonary function improved significantly. FEV1 increased from 0.68 +/- 0.2 to 1.0 +/- 0.2 L (p < 0.01) and FVC increased from 1.7 +/- 0.5 to 2.7 +/- 0.5 L (p < 0.017). Total lung capacity decreased from 129% +/- 24% to 108% +/- 20% (p < 0.03). 6-min walk increased from 221 +/- 90 to 404 +/- 123 meters (p < 0.001). Complications included 1 death, prolonged air leak in 7 cases and infection in 2. Quality of life improved substantially in 12 of the 16 cases; in 3 cases there was only slight improvement and in 1 the condition became worse. Volume reduction surgery is a promising surgical solution in selected patients with advanced emphysema.

Adult↗

Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung.

1. During fetal life the lung develops as a liquid-filled organ. This liquid is produced by the fetal lung and leaves via the trachea from where it is either swallowed or enters the amniotic sac. Fetal lung liquid plays a crucial role in the growth and development of the lungs by maintaining them in a distended state. It is now recognized that the retention of liquid within the future airways is required to maintain the lungs at an appropriate level of expansion in order to stimulate their growth. Indeed, it is likely that most, if not all, of the conditions and malformations that lead to inadequate growth of the fetal lung do so by reducing the volume of lung liquid and hence the degree of lung expansion. 2. The volume of fetal lung liquid is principally regulated by the resistance to lung liquid efflux through the fetal upper airway and by the presence of diaphragmatic activity associated with fetal breathing movements (FBM). During non-breathing periods, the relatively high resistance offered by the upper airway to the efflux of lung liquid opposes the loss of liquid from the lung, thereby maintaining fetal lung expansion. During episodes of FBM, when the larynx is actively dilated and the resistance to lung liquid efflux is reduced, lung liquid leaves the lungs at an increased rate. However, selective inhibition of diaphragmatic muscle activity in the foetus leads to a reduction in lung liquid volume, rather than an increase. This finding indicates that during periods of FBM, rhythmical contractions of the diaphragm retard the loss of lung liquid and help to maintain lung expansion when the upper airway resistance is reduced. It is now apparent that the maintenance of lung expansion by FBM is the basis for their role in promoting fetal lung growth. 3. Successful transition from intra-uterine to extra-uterine life is dependent upon the clearance of liquid from the fetal lungs at the time of birth so that the lungs may effectively function as an organ of gas exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Baclofen-induced block of the Hering-Breuer expiratory-promoting reflex in rats.

Baclofen, a gamma-aminobutyric acid (GABA) agonist acting on GABAB receptors, has profound effects on respiratory function. We tested a hypothesis that GABAB receptors are involved in modulation of the respiratory reflexes mediated by pulmonary slowly adapting stretch receptors. Urethane-anesthetized (1.2-1.6 g/kg; i.p.) Wistar rats with body weight 230-320 g were breathing room air supplemented with oxygen. The gas mixture was applied to the T-shaped tracheal cannula at a flow rate of 1.5 L/min. The head of the animals was mounted in a stereotaxic apparatus, and the medulla was exposed. We recorded integrated diaphragmatic EMG (Di) and tracheal and arterial blood pressures. Injections of 100 nL of saline into the nucleus tractus solitarii (NTS) preceded injections of 60 or 110 pmol baclofen in group 1 (n = 14), and 2.8 nmol CGP 35348, a GABAB receptor antagonist, in group 2 (n = 5). Saline had no effects on baseline Di. Occlusion of the tracheal cannula caused an increase in tracheal pressure to 8 cmH2O (1 cmH2O = 98.1 Pa) and provoked a prolongation of expiration (the Hering-Breuer expiratory-promoting reflex) in all drug-free rats. Baclofen abolished the Hering-Breuer reflex in all rats. CGP 35348 reversed the block of the reflex. In group 2, CGP 35348 prevented the effects of baclofen, and alone did not affect respiration. These results support our hypothesis and suggest that GABAB receptors are present on the medullary pathway of slowly adapting mechanoreceptor input. However, GABAB receptors in the rat NTS may not be involved in modulation of the fundamental respiratory function.

Animals↗

High-frequency intratracheal pulmonary ventilation: improved gas exchange at lower airway pressures.

PURPOSE: Conventional ventilation in the neonatal intensive care unit causes iatrogenic injury to fragile newborn lungs, especially those with preexisting pathology or prematurity. Intratracheal pulmonary ventilation (ITPV), developed by Dr Theodor Kolobow and associates at the National Institutes of Health (NIH), incorporates a continuous flow of humidified gas through a reverse thrust catheter positioned at the distal end of the endotracheal tube. In animal studies ITPV was shown to facilitate gas exchange at low peak pressures by reducing physiological dead space, facilitating exhalation, and enhancing CO2 elimination. The specific aims of this project were (1) to invent a new ITPV-specific ventilator; (2) to optimize gas exchange in a newborn animal model at low airway pressures using higher frequency ITPV; and (3) to demonstrate efficacy and improved ventilation at lower airway pressures in a prematurity model. METHODS: (1) A new ventilator had to be constructed. The first prototype is microprocessor driven, incorporating controls for flow, pressures, and concentrations of gases. The ventilator has the capability to vary Fio2, respiratory rate (0 to 15 Hz), and inspiratory-expiratory I:E ratio. (2) Prototype testing was performed. Newborn lambs (n = 3, 6 to 7 kg) underwent tracheotomy and placement of arterial and venous lines. Lambs were initially supported on conventional mechanical ventilation (CMV). Animals were allowed to achieve steady state with measurements of baseline vital signs, arterial blood gases, and ventilatory settings. ITPV was instituted at a rate of 100 breaths per minute and flow adjusted to achieve lower peak carinal pressures than obtainable on conventional ventilation. In a stepwise fashion, respiratory rate, I:E ratio, and ITPV flows were varied while initially maintaining Paco2 constant, and then allowing improvement. (3) These experiments were repeated in preterm lambs (n = 6, 1.8 to 3.6 kg). RESULTS: At the time of transition from CMV to ITPV (rate, 100, I:E, 1:3), gas exchange was maintained despite a documented drop in average peak carinal pressure for the newborn lambs from 28.3 cm H2O on CMV to 10.3 cm H2O on ITPV (P = .028). The average peak carinal pressure fell even further at higher ITPV rates with adjustments in I:E ratio. For the premature lambs, peak carinal pressures also fell significantly on ITPV (44 to 32 cm H2O, P = .002) with corresponding significant improvement in ventilation (Paco2 from 52.2 to 31.9 mm Hg, P = .029). CONCLUSIONS: (1) Our new ITPV ventilator operates at rates and I:E ratios previously unobtainable. (2) In newborn and premature lambs ITPV functions most effectively at higher rates with higher gas flow rates and with longer exhalation, providing significantly improved gas exchange at significantly lower peak carinal pressures. (3) ITPV may prove beneficial in achieving gas exchange in newborns while avoiding barotrauma. Based on these data, we have initiated human clinical studies of ITPV in newborns with congenital diaphragmatic hernia or prematurity to improve gas exchange and reduce barotrauma in the neonatal intensive care unit.

Animals↗

Abnormal vascular tone in infants and children with lung hypoplasia: Findings from cardiac catheterization and the response to chronic therapy.

OBJECTIVE: We describe four cases of chronic pulmonary hypertension in infants and children with chronic lung disease and pulmonary hypoplasia due to severe congenital diaphragmatic hernia (CDH) or congenital cystic adenomatoid malformation (CCAM). We report data from cardiac catheterization under various conditions: baseline respiratory support and room air, hyperoxic and inhaled nitric oxide challenge. We further report cardiac catheterization measures after chronic pulmonary vasodilator therapy with sildenafil alone or a combination of sildenafil and inhaled nitric oxide (three patients). DESIGN: Case series. SETTING: Tertiary academic center. PATIENTS: Infants and children ages 0-11 yrs with CDH (n = 3) or CCAM (n = 1) with evidence of chronic pulmonary hypertension by echocardiogram and cor pulmonale (n = 3). INTERVENTIONS: Catheterization and pulmonary vasodilator therapy. MEASUREMENTS AND MAIN RESULTS: Pulmonary vascular resistance, pulmonary arterial pressure, and changes in these measures were assessed. A 20% change in pulmonary vascular resistance was considered a clinically significant response. Ten catheterizations were performed in four patients. All patients had elevated pulmonary vascular resistance and pulmonary arterial pressures at initial catheterizations and significant vasodilation during inhaled nitric oxide. CONCLUSIONS: Chronic lung disease following pulmonary hypoplasia from CDH and CCAM is associated with abnormal pulmonary vascular tone in infants and children with evidence of chronic pulmonary hypertension. Chronic pulmonary vasodilator therapy may improve pulmonary vascular function and enhance lung growth in infants and children who are treated during their period of potential for rapid lung growth.

Cardiac Catheterization↗

Respiratory volume-timing relationship during sustained elevation of functional residual capacity.

In 7 spontaneously breathing dial-urethane anesthetized cats a negative pressure was produced around the thorax and abdomen to increase the functional residual capacity (FRC) by about 1 tidal volume for up to 60 min. A tracheal cannula was connected to a resistive manifold for selective loading of inspiration or expiration. Two resistive loads and tracheal occlusion were presented six times each at control FRC (FRCc), after 60 min at elevated FRC (FRCe) and 30 min after return to FRCc. Inspiratory and expiratory durations (TI and TE) were measured from diaphragmatic EMG. We observed that TI at FRCe (0.88 +/- 0.11 sec) was not significantly shorter than TI at FRCc (1.06 +/- 0.14 sec). Tracheal occlusion at FRCe caused a shorter TI (1.37 +/- 0.15 sec) than at FRCc (1.79 +/- 0.21 sec) (P less than 0.05). The slope (m) of the VI-TI relationship generated by the resistive loads at FRCe was steeper (m = -65 +/- 7 ml X sec-1) and shifted upward from the VI-TI curve at FRCc (-50 +/- 6 ml X sec-1) (P less than 0.05). The VE-TE relationship at FRCe was not significantly changed from control. Thirty minutes following return to FRCc, TI was still slightly shorter (0.96 +/- 0.11 sec) than the initial TI at FRCc. We conclude: (1) The slope of the VI-TI relationship is determined to a great extent by the total lung volume. However, under the conditions of sustained elevation of FRC, this relationship is influenced by the partial adaptation of slowly adapting pulmonary receptors SARs. (2) The increased SAR activity at end expiration during FRCe may not influence the control of TE.

Animals↗

[The effect of sedation on pulmonary function].

Opioids, benzodiazepines and hypnotics all affect central respiratory drive, muscular activity of the oropharynx, thoracic wall and diaphragm, bronchomotor tone and pulmonary vascular resistance (PVR), and may thus influence respiratory function during sedation and weaning. Opioids and benzodiazepines will attenuate hypercapnic and hypoxic stimulation of the respiratory centres. Compromise of respiratory drive must also be anticipated with ketamine, in view of recent evidence contradicting earlier findings of central respiratory stimulation. Coordinated muscular activity of the oropharynx is important for airway patency. Since this mechanism is impaired more by benzodiazepines than by ketamine the latter may be advantageous during weaning. Respiratory frequency and tidal volume are both diminished by opioids, benzodiazepines and propofol. The differential impact on intercostal and diaphragmatic muscle activity may prove important in COPD and emphysema. With ketamine spontaneous respiration is increased. Gas distribution and airway pressures are influenced by bronchomotor tone. Bronchodilator effects are well known to arise with ketamine, but have also been demonstrated with benzodiazepines, propofol and some opioids. PVR is a critical factor in respiratory insufficiency. An increase in PVR with ketamine has been found during spontaneous respiration. Since evidence for pulmonary vasodilation during controlled ventilation has been recorded in humans and in vitro experiments, sedation regimens applied in respiratory insufficiency can also include ketamine.

Analgesics↗

Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic.

BACKGROUND/PURPOSE: In 1990, the authors began a multidisciplinary follow-up clinic for congenital diaphragmatic hernia (CDH) patients. Although the nonpulmonary complications associated with CDH have been reported previously from this clinic, the purpose of this report is to detail the pulmonary outcome in survivors of CDH with severe pulmonary hypoplasia. METHODS: Between 1990 and 1999, one hundred patients were seen in the clinic. Before hospital discharge, all patients had baseline tests performed, which were repeated per protocol at clinic during follow-up. The data were analyzed by regression analysis to identify and determine the impact of factors on outcomes associated with the long-term pulmonary morbidity. RESULTS: The average birth weight was 3.16 kg (+/-0.7) with a mean Apgar score of 7 (+/- 2) at 5 minutes. Forty-one patients had an antenatal diagnosis performed. Extracorporeal membrane oxygenation (ECMO) was utilized in 29 patients, and a patch repair was required in 32, whereas 16 patients received both. Average time to extubation was 20.7 (+/- 20) days and mean time to discharge was 59.7 (+/- 61) days. Regression analysis showed that both the need for ECMO and a patch repair were independent predictors of delay in extubation (P <. 001, R(2) = 36%), and delay in discharge from the hospital (P =.001, R(2) = 29%). ECMO also was significantly correlated with the need for diuretics at discharge (P <.001, R(2) = 18%), and with the presence of left-right mismatch (P =.009, R(2) = 9%) and V/Q mismatch (P =.005, R(2) = 11%) on subsequent pulmonary ventilation-perfusion examinations. Sixteen patients required O(2) at discharge, and diuretics were necessary in 43 patients. Seventeen patients at discharge required bronchodilators, and during the first year an additional 36 required at least transient therapy. Similarly, 6 patients at discharge required steroids, and an additional 35 patients required at least transient therapy during the first year. Chest x-rays, although frequently abnormal, had little correlation with clinical outcome, but did influence medical therapy. V/Q scans had limited utility in patient management, and the presence of V/Q mismatch was not highly specific for future obstructive airway disease. Nevertheless, V/Q mismatch was sensitive for obstructive airway disease assessed by spirometry. Twenty-five patients over 5 years of age performed pulmonary function tests (PFTs), which showed 72% normal PFT results and 28% with evidence of obstructive airway disease. Before January 1997, 2 of 8 patients who required urgent treatment in the emergency department (ED) were admitted to the intensive care unit (ICU) secondary to acute respiratory distress. After the implementation of respiratory syncytial viral prophylaxis in January 1997, 8 patients were treated in the ED for acute respiratory distress, but none required admission to the ICU. CONCLUSIONS: Pulmonary problems continue to be a source of morbidity for survivors of CDH long after discharge. The need for ECMO and the presence of a patch repair are both predictive of more significant morbidity, but the data clearly show that non-ECMO CDH survivors also require frequent attention to pulmonary issues beyond the neonatal period. These data show the need for long-term follow-up of CDH patients preferably with a multidisciplinary team approach.

Extracorporeal Membrane Oxygenation↗

Nutritional supplementation for stable chronic obstructive pulmonary disease.

BACKGROUND: Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES: To conduct a systematic review of randomised controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. Searches are current as of March 2004. SELECTION CRITERIA: Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS: Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS: Eleven studies recruiting 352 participants met the inclusion criteria. Eight papers were considered as high quality. Two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. AUTHORS' CONCLUSIONS: Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.

Enteral Nutrition↗

Kinematic modeling of single muscle fiber during diaphragm shortening.

Understanding the kinematics of the diaphragm muscle at the single fiber level is important in understanding the mechanics of its membrane. Nevertheless, the geometric parameters of single muscle fiber contraction remain poorly understood. We modeled the kinematics of a single muscle fiber of the diaphragm to determine the relationships among fiber shape, perimeter of the fiber cross-section, and apparent surface area of the fiber during muscle shortening. We used the models to identify which constraints on the geometric parameters are most consistent with physiological data on diaphragmatic muscle shortening. Our kinematic models use isovolumic fibers with elliptical cross-sections, and these models have the following properties: (1) constant cross-sectional shape, (2) inextensible cross-sectional perimeter, (3) constant cross-sectional transverse dimension, or (4) constant apparent surface area. These models were investigated during muscle shortening of the diaphragm from functional residual capacity to total lung capacity. The model that matches physiologic data best has zero transverse strain and has a relationship between fiber shape and muscle shortening consistent with published data on single muscle fiber mechanics.

Anatomy, Cross-Sectional↗

Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema.

BACKGROUND: Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. METHODS: We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. RESULTS: Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with alpha1-antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P = 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/F(I)O2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9+/-14.6 hours vs 40.4+/-3.9, P = 0.02, ANOVA) and longer lengths of stay (19.3+/-2.1 days vs 13.7+/-1.3, P = 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. CONCLUSION: Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation.

Acute Disease↗

Effects of diaphragm shortening on the mean action potential conduction velocity in canines.

1. The present study was designed to test if the mean muscle fibre action potential conduction velocity (VAPC) in the costal diaphragm changes with muscle length, in spontaneously breathing mongrel dogs. 2. VAPC was determined by the electromyogram (EMG) power spectrum 'dip' method, which is based on the bipolar electrode transfer function. A bipolar EMG electrode with a 20 mm fixed interelectrode distance was sutured to the costal diaphragm in the fibre direction, and in a region with a low density of motor endplates. Diaphragm length was measured with piezoelectric crystals positioned next to the EMG electrode. Seven dogs were vagotomized and spinally anaesthetized in order to increase diaphragmatic shortening, reduce velocity of shortening and abolish possible cross-talk signals from adjacent muscles. 3. Our results showed that VAPC in the canine costal diaphragm was 3.4 m s-1 and was not significantly related to diaphragmatic shortening.

Action Potentials↗

Mechanics of the canine diaphragm.

Diaphragmatic force-length behavior was assessed in anesthetized dogs using two techniques. One employed measurements in a diaphragm strip with intact nerve and blood supply; the second related transdiaphragmatic pressure (Pdi) to direct estimates of diaphragmatic tension from strain gauge arches during bilateral, tetanic, supramaximal phrenic nerve stimulation. In strip preparations the diaphragm exerted active force at lengths as short as 40% of resting in situ length (Lo), and maximal force was registered at a length averaging 25% greater than Lo. This suggested a broader effective length range for the diaphragm as compared to other skeletal muscles. In the intact preparation both Pdi and directly measured diaphragmatic tension were inversely related to lung volume and when they were used to calculate the diaphragm's effective radius of curvature (r), r was found to change little or decrease at large lung volumes rather than increase as theory would predict. These findings suggest that length tension characteristics outweigh geometric considerations in explaining the diaphragm's function in normal dogs and probably normal men.

Animals↗

Ventilatory muscle dysfunction in patients with bilateral idiopathic diaphragmatic paralysis: reversal by intermittent external negative pressure ventilation.

Bilateral idiopathic diaphragmatic paralysis (BIDP) may result in progressive ventilatory failure. To test the hypothesis that this is in part due to dysfunction of overtaxed inspiratory muscles, we studied 3 patients with BIDP before and after 2, 5, and 18 wk of daily intermittent external surface negative pressure ventilation (ENPV). The patients were evaluated using a zero to 10 functional score (FS) that graded dyspnea, orthopnea, capacity to perform activities of daily living, and ability to work. Pleural (Ppl), abdominal (Pab), and transdiaphragmatic (Pdi) pressures were used as an index of respiratory muscle function. All patients improved their functional score (FS increased 2, 6, and 6, respectively) and their pressure generating ability (Pplmax increased -18, -37, and -46 cm H2O, respectively). Forced vital capacity and functional residual capacity increased in the 2 patients ventilated for longer than 2 wk. These results indicate that ventilatory muscle dysfunction may result from chronic increased work of the inspiratory muscles and that it may improve after periods of intermittent ENPV. This may occur as early as 2 wk after initiation of therapy.

Adult↗

Effect of free radical scavengers on endotoxin-induced respiratory muscle dysfunction.

Recent studies have suggested that free radicals contribute to the diaphragmatic dysfunction observed in sepsis. However, previous work has not determined which species of free radicals are responsible for producing these effects or whether the intercostal muscles are affected similarly during sepsis. The purpose of this study was to examine these issues using a hamster model of endotoxin-mediated sepsis in which diaphragm and intercostal muscle function was assessed on muscle strips excised from these animals after killing. Several groups of animals were studied, including animals injected with (1) saline, (2) endotoxin, (3) endotoxin plus active PEG-SOD, a superoxide scavenger, (4) endotoxin plus active PEG-catalase, a hydrogen peroxide scavenger, (5) endotoxin plus DMSO, a hydroxyl scavenger, and (6) endotoxin plus denatured PEG-SOD. We found that endotoxin administration elicited significant reductions in diaphragm and intercostal muscle contractility. In each of the three groups of animals to which active free radical scavengers were administered, the effects of endotoxin were attenuated. Denatured PEG-SOD did not protect the respiratory muscles from endotoxin-mediated dysfunction, however. These data indicate that both the diaphragm and intercostal muscles are affected similarly by sepsis; moreover, several free radical species (superoxide ions, hydrogen peroxide, and hydroxyl ions) play a role in mediating this type of injury.

Animals↗

Nutritional support for individuals with COPD: a meta-analysis.

RATIONALE: Malnutrition in patients with COPD is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity, and higher mortality rate when compared to adequately nourished individuals with COPD. Nutritional support may therefore be a useful part of their comprehensive care. PURPOSE: To conduct a meta-analysis of randomized controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength, and functional exercise capacity in patients with stable COPD. METHODS: RCTs were identified from several sources, including the Cochrane Airways Group register of RCTs, a hand search of abstracts presented at international meetings, and consultation with experts. Two reviewers independently selected trials for inclusion, assessed quality, and extracted the data. Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. RESULTS: From 272 references, nine RCTs were ultimately included. Six articles were considered as high quality. Only two studies were double blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. CONCLUSION: Nutritional support had no effect on improving anthropometric measures, lung function, or functional exercise capacity among patients with stable COPD.

Combined Modality Therapy↗