Synergistic behavior of inspiratory muscles after diaphragmatic fatigue in the newborn

We studied diaphragmatic and intercostal muscle activity and the pattern of motion of rib cage and abdomen after diaphragmatic muscle fatigue in 15 newborn infants (birth wt 1,251 +/- 424 g, mean +/- SD). Rib cage and abdominal motion were monitored with magnetometers and intercostal and diaphragmatic electromyograms (EMG's) with surface electrodes. Twelve infants showed a total of 66 episodes of muscle fatigue identified by EMG frequency spectrum analysis. Two patterns of responses to fatigue were observed. In the first case, five infants consistently recruited their intercostal muscles; this was followed by a normalization of the diaphragmatic frequency spectrum. In these infants, recruitment of intercostal muscles successfully prevented any clinical deterioration. In the second, seven infants showed no change in their intercostal muscle activity, and diaphragmatic fatigue was followed by apnea. We conclude that in newborn infants the synergistic behavior of the diaphragm and intercostal muscles can maximize the performance of these muscles and, in some infants, seems to prevent development of apnea.     

Determinants of the tension-time index of inspiratory muscles in children with cystic fibrosis

1. Hypertension secondary to renal disease was studied in non-pregnant and pregnant ewes to determine whether there were any changes in arterial pressure and the distribution of cardiac output and, in particular, whether uteroplacental blood flow was affected. 2. In six non-pregnant, chronically catheterized, uninephrectomized ewes, a reduction in renal blood flow (RBF) to 40-50% of control caused hypertension within 3 h. This was maintained for as long as RBF was reduced (72 h) and returned to control 24 h after the occluder around the renal artery was released. When this experiment was repeated in 16 uninephrectomized pregnant ewes (118-134 days gestation) hypertension occurred within 3 h and was sustained for as long as RBF was reduced (between 24 and 72 h). Arterial pressure returned to control within 24-72 h of restoring RBF. 3. Compared with non-pregnant ewes, pregnant ewes had similar arterial pressures, higher cardiac outputs (CO; P < 0.001) and heart rates (HR; P < 0.001), lower total peripheral resistances (TPR; P < 0.001) and similar blood flows to brain, ovary, pancreas, kidney and spleen. Splenic vascular resistance (VR) was greater (P = 0.006), gut blood flow was greater (P < 0.05) and gut VR was less (P < 0.05). Myoendometrial blood flow/g was greater (P < 0.005) and myoendometrial VR was less (P = 0.006). 4. In pregnant sheep with renal clip hypertension, there was no change in CO and HR, but TPR increased (P < 0.01), as did plasma renin activity. Gut, brain, pancreatic and myoendometrial VR were increased as long as RBF was reduced; in addition, myoendometrial VR remained high for the rest of the experiment. Placental blood flow was unchanged at 3 h; 24-72 h later it was reduced (P < 0.05) and remained low. Placental VR was increased 24-72 h after RBF was restored when ewes were again normotensive. 5. Thus, one-clip, one-kidney renal hypertension in the pregnant ewe was due to increased TPR associated with a fall in uteroplacental blood flow that persisted even when RBF was restored and ewes were normotensive. This reduction in uteroplacental blood flow could account for the high foetal morbidity and mortality that occurs in pregnant women with renovascular hypertension.     

Effect of hypoxia on the pressure developed by inspiratory muscles during airway occlusion

Patients with colitis and ileocolitis of unknown etiology from two previously reported series have been combined and the follow-up studies have been extended to compare the long term postoperative courses of ulcerative colitis (UC) and Crohn's disease of the colon (CDC). The combined and updated series of 176 patients, 99% of whom could be traced, provided a mean postoperative follow-up period for UC of 14 years (5 to 31) and CDC of 13.1 years (5 to 36). There were highly significant associations between generally accepted clinical and distributional features of UC and CDC and microscopic findings generally regarded as reliable for each. However, because of spectrum of features was found in each entity, neither clinical and distributional nor microscopic features alone are sufficient for diagnosis in every case. There were no differences in gross or disease-related mortality in UC and CDC whatever the method of diagnosis. After anastomotic procedures in CDC a recurrence rate of 73% was found. After proctocolectomy the ileostomy revision rate (considering all types of those which required further excision of ileum) was higher in CDC than UC whether the diagnoses were based on microscopic, clinical, or combined criteria, but the differences reached statistical significance only in the comparison of "clinical UC", with "clinical CDC". Moreover, after the first 2 postoperative years, the risk of having an ileostomy revision in UC and CDC (combined criteria) per patient year follow-up was virtually identical and there were no cases of short bowel syndrome. Differences in the clinical courses of UC and CDC after colectomy and ileostomy are of degree and do not reflect the ultimate course or potential for rehabilitation. Decisions regarding surgical therapy should be made independent of the diagnosis of UC or CDC.     

Lung volume reduction surgery for severe emphysema

In hairless mice, a moderate vitamin-A deficiency, without any clinical signs or weight changes, reduces the activity of soluble cytoplasmic hepatic transglutaminase without affecting the membrane form of the enzyme. This attack of soluble transglutaminase appears to be a biological marker of early deficiency. The relations between this disturbance and the hepatocyte sensitivity to aggressors at this stage are discussed.     

Lung volume reduction surgery for severe emphysema

BACKGROUND: We report mid-term results after 25 consecutive lung volume reduction operations (LVRS) for the treatment of severe dyspnea due to advanced emphysema. METHODS: Study design: patients were studied prospectively up to 12 months after surgery. Setting: preoperative evaluation, surgery and postoperative care took place in our university hospital. Patients: patient selection was based on severe dyspnea and airway obstruction despite optimal medical treatment, lung overinflation and completed rehabilitation programme. Patients with severe hypercarbia (PCO2>50 mmHg) were excluded. Nineteen rehabilitated patients who fulfilled our inclusion criteria but postponed or denied LVRS were followed up clinically. Interventions: LVRS was performed bilaterally in 22 patients (median sternotomy) and unilaterally in 3 patients (limited thoracotomy). Measures: Outcome was measured by dyspnea evaluation, 6-minute-walking distance and pulmonary function tests. RESULTS: Twelve months postoperatively dyspnea and mobility improved significantly (MRC score from 3.3+/-0.7 to 2.12+/-0.8, 6-min-walk from 251+/-190 to 477+/-189 m). These results were superior compared to the results of the conservatively treated patients. Significant improvement could also be documented in airway obstruction (FEV1 from 960+/-369 to 1438+/-610 ml) and overinflation (TLC from 133+/-14 to 118+/-21% predicted and RV from 280+/-56 to 186+/-59% predicted). CONCLUSIONS: LVRS is an effective and promising treatment option for selected patients with end-stage emphysema and could be offered as an alternative and / or bridge to lung transplantation.     

Lung volume reduction surgery as an emergency and life-saving procedure

Lung volume reduction surgery (LVRS) is emerging as a promising and unique therapeutic option for rigorously selected patients with severe debilitating emphysema. A 51 yr old man with generalized emphysema developed bilateral pneumothoraces during his first holiday abroad. Due to respiratory insufficiency, intubation and mechanical ventilation were necessary. In total, six chest tubes were inserted but massive air leak persisted and his respiratory condition deteriorated due to bronchopneumonia and sepsis. The patient was transferred to Belgium. As a last resort, bilateral LVRS was performed through a median sternotomy. The most diseased areas of the upper lobes containing the air leak were resected bilaterally and a pleurectomy was associated. Three months after operation, there was a remarkable improvement in spirometric values with an increase in forced expiratory volume in one second of almost 100%. The results were sustained after a follow-up of 18 months. In this dramatic case, lung volume reduction surgery proved to be effective, and was even a life saving procedure.     

Effects of fenoterol on inspiratory effort sensation and fatigue during inspiratory threshold loading

We studied the effects of a single dose of fenoterol on the relationship between inspiratory effort sensation (IES) and inspiratory muscle fatigue induced by inspiratory threshold loading in healthy subjects. The magnitude of the threshold was 60% of maximal static inspiratory mouth pressure (PI,mmax) at functional residual capacity, and the duty cycle was 0.5. Subjects continued the threshold loaded breathing until the target mouth pressure could no longer be maintained (endurance time). The intensity of the IES was scored with a modified Borg scale. Either fenoterol (5 mg) or a placebo was given orally 2 h before loading in a randomized double-blind crossover protocol. The endurance time with fenoterol (34.4 +/- 8.6 min) was longer than that with the placebo (22.2 +/- 7.1 min; P < 0.05). The ratio of high- to low-frequency power of the diaphragmatic electromyogram (EMGdi) decreased during loading; the decrease was less with fenoterol (P < 0.05). The EMGdi also decreased with loading; the decrease was greater on fenoterol treatment (P < 0.01). The PI,mmax and maximal transdiaphragmatic pressure (Pdi) were similarly decreased after loading on either treatment. The intensity of the IES rose with time during loading in both groups but was lower with fenoterol than with the placebo (P < 0.05). The ratio of Pdi to integrated activity of the EMGdi increased with fenoterol (P < 0.05). Fenoterol treatment increased both superimposed Pdi twitch and Pdi twitch of relaxed diaphragm and decreased the value of (1-superimposed Pdi twitch/Pdi twitch of relaxed diaphragm). Thus we conclude that in normal subjects fenoterol reduces diaphragmatic fatigue and decreases the motor command to the diaphragm, resulting in a decrease in IES during inspiratory threshold loading and a prolongation of endurance.     

Lung volume reduction or lung transplantation for end-stage pulmonary emphysema?

OBJECTIVE: As the waiting period for lung transplant (LT) candidates with end-stage pulmonary emphysema (COPD) continues to increase, there is a need for alternative treatments to reduce the morbidity and mortality associated with COPD. We hypothesized that lung reduction (LR) may avoid the need for subsequent LT in patients on the waiting list that are also candidates for LR. METHODS: From July 1994 to December 1995, 20 patients received LR as alternative to LT. The average age was 58 +/- 7 years; 11 were males. Eighteen patients had primary COPD and two had alpha-1 antitrypsin deficiency. Eighteen LRs were thoracoscopic (two bilateral and 16 unilateral) and two were done through a median sternotomy. RESULTS: At a follow-up of 32 +/- 4 months, 19 patients are alive (19/20 = 95%). Fifteen patients (15/20 = 75%) are currently off the LT list and doing well: FEV1 is 40 +/- 18% predicted at 2 years compared with 22.7 +/- 6% before LR (P < 0.001); FVC is 84 +/- 13% at 2 years compared with 55 +/- 7% (P < 0.001) and the RV is 145 +/- 59% compared with 270 +/- 58% (P < 0.001). One patient (5%) required extra-corporeal membrane oxygenation (ECMO) after LR to the contralateral side of the first procedure and subsequently died. Two patients (10%) are currently listed for LT because of persistent symptoms. One patient (5%) in whom deterioration was secondary to exposure to toxic fumes, underwent successful LT. One patient (5%) is doing well from the pulmonary standpoint but is being worked up for new severe coronary artery disease (CAD). The freedom from LT is 95% (19/20) and the freedom from repeat LR is 85% (17/20). CONCLUSIONS: LR has the potential to offer an effective palliative alternative to LT in 75% of selected patients up to 32 months of follow-up. Widespread use of bilateral LR is anticipated to further improve the results.     

Defensiveness and perception of external inspiratory resistive loads in asthma

This paper introduces a model which incorporates fetal thymus organ culture (FTOC) from NOD mice to replicate thymic development of diabetogenic T cells. NOD fetal pancreas organ culture (FPOC) co-cultured with 13-16 day NOD FTOC for an additional 14-21 days produced less insulin than FPOC cultured alone. Insulin production from the FTOC of non-diabetic strains C57BL/6 and BALB/c was not inhibited by co-culture with FTOC from their syngeneic counterparts. Sections of the NOD co-cultures showed peri-islet infiltration with lymphocytes. Insulin reduction by FTOC/FP co-culture was prevented by co-culture of the NOD FT with FT from immunologically incompetent C.B-17 SCID/SCID mice. Co-culture of NOD FP with NOD FT prior to the development of T cells prevented generation of diabetogenic FTOC. Thus, early exposure of NOD T cell precursors to the thymic stromal elements of C.B-17 SCID/SCID FT or to islet antigens can negatively select for diabetogenic T cells or activate immuno-regulatory cells that can suppress diabetogenic T cell activity. The addition of blocking F(ab')2 fragments of anti-CD3epsilon monoclonal antibody to NOD FTOC/FP co-cultures prevented insulin reduction, implicating a role for TcR-mediated recognition in this "in vitro IDDM" model. The addition of activating whole anti-CD3epsilon caused the complete ablation of insulin production in FTOC/FP co-cultures from all strains tested. Transfer of unprimed syngeneic FTOC cells to prediabetic NOD mice prevented the onset of IDDM while transfer of islet-cell primed FTOC/FP cells slightly increased disease incidence. These data suggest that while diabetogenic T cells are present in the FT, they are normally suppressed, even after organ culture. However, these cells can induce the destruction of islet cells, in vitro and in vivo, if they are appropriately activated with pancreatic tissue.     

The effect of positive endexpiratory pressure, peak inspiratory pressure, and inspiratory time on functional residual capacity in mechanically ventilated preterm infants

In mechanical ventilation of preterm infants, positive endexpiratory pressure (PEEP) is widely used to prevent alveolar collapse, maintain functional residual capacity (FRC) and improve oxygenation. Prolongation of inspiratory time (ti) and increase of peak inspiratory pressure (PIP) are also used for this purpose. We investigated the effect of variations of PEEP, PIP and ti on FRC in ten infants with hyaline membrane disease and onset of bronchopulmonary dysplasia (BPD, n = 7), pulmonary hypertension (n = 1), pulmonary hypoplasia (n = 1) or severe BPD (n = 1) (gestational age 24-39 weeks, median 26 weeks; birth weight 590-2960 g, 785 g; chronological age 7 84 days, 19 days; weight 689-4650 g, 1185 g). FRC, measured using the sulphur hexafluoride washout technique, was between 6.2 and 48.3 ml/kg (median 21.5 ml/kg). PEEP was changed stepwise 2-5 times in each patient (median 3) and mean airway pressure (MAP) was modified independently of PEEP by changing PIP 0 2 times (median 1) and ti 0(2 times (median 2). Changes of FRC correlated well with modifications of PEEP in each patient (r = 0.90, range 0.71 0.99). The slope factors of linear correlations had a median value of 2.94 ml/cm H20 per kg, which was significantly different from zero (P < 0.01) and significantly higher than the slope factors of linear correlations between FRC and MAP after modifications of PIP or ti (P < 0.01). The latter two were statistically not different from zero. The quotients deltaFRC/deltaMAP were significantly higher after adjustments of PEEP than after adjustments of PIP or ti (P < 0.01). The time lag between the change of PEEP and the stabilization of FRC on a new level ranged from 2 to 14 min (median 5). CONCLUSION: FRC is mainly determined by PEEP but not by PIP or ti. Stabilization of FRC after a change of PEEP can last up to 14 min. Its duration is unpredictable and has to be waited for when testing pulmonary function in ventilated preterm infants.     

High-frequency oscillation and centroid frequency of diaphragm EMG during inspiratory loading

Exposure of progenitor cells with chondrogenic potential to recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7] may be of therapeutic interest in the regeneration of articular cartilage. Therefore, in this study, we examined the influence of rhOP-1 on cartilage formation by human perichondrium tissue containing progenitor cells with chondrogenic potential in vitro. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [³5;S]sulfate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [³5;S]sulfate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microgram/ml. Histology revealed that explants treated with 20-200 microgram/ml rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. These results suggest that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells to stimulate chondrocytic differentiation and production of cartilage matrix in vitro provide a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus, rhOP-1 may promote early steps in the cascade of events leading to cartilage formation. Therefore, rhOP-1 could be an interesting factor for regeneration of cartilage in articular cartilage defects.     

The study of maximal nasal inspiratory flow in humans

During inspiration through one nostril, airflow becomes limited to a maximal level (VImax) when the transmural pressure (Ptm) at a flow-limiting site (FLS) falls below a critical level (Ptm'). We compared two methods for measuring the Ptm' of the nasal FLS. Each of six subjects (four normal and two with allergic rhinitis out of season) performed multiple inspirations through one nostril as we varied the resistance at the nasal opening. Studies were performed after application of a topical decongestant without activation of the alae nasi. We determined Ptm' by regressing the resulting values of VImax on the corresponding transnasal pressure gradients (Regression Method). We also measured Ptm' directly using pressure catheters to measure the pressure surrounding the FLS and the lateral pressure near the FLS at VImax (Catheter Method). The mean value of Ptm' by the Regression Method was -3.8 +/- 3.2 (SD) cmH2O. The value by the Catheter Method with the catheter just downstream from the nasal FLS was -3.5 +/- 2.9 cmH2O, which correlated closely with the Ptm by the Regression Method (r = 0.98). Our findings suggest that the Ptm' of the nasal airway can be determined by either method. The Catheter Method, however, requires only one inspiratory effort for each determination and simultaneously localizes the nasal FLS.     

Load dependence of secondary diaphragm inflammation and injury after acute inspiratory loading

Neural transplantation as an experimental therapy for Parkinsonian patients has been shown to be effective in several clinical trials. Further benefit, however, may be expected if the grafting is combined with a treatment of neurotrophic factors thus improving the survival and growth of grafted embryonic dopaminergic neurons. Continuous trophic support may be needed and therefore requires the long-term delivery of neurotrophic factors to the brain. We demonstrate here that the implantation of polymer-encapsulated cells genetically engineered to continuously secrete glial cell line-derived neurotrophic factor to the adult rat striatum improves dopaminergic graft survival and function. Near complete compensation of 6-hydroxydopamine-induced rotation was already achieved within 3 weeks postgrafting in rats that received glial cell line-derived neurotrophic factor-releasing capsules in addition to dopaminergic cell grafts of cultured tissue. Rats without trophic factor supply showed only little recovery at the same time point and sham grafted rats showed no recovery. The number of tyrosine hydroxylase-immunoreactive cells per graft was increased 2.6-fold in the presence of glial cell line-derived neurotrophic factor 6 weeks postgrafting. Similarly, tyrosine hydroxylase-immunoreactive fibers around the graft were increased by 53%. Moreover, these fibers showed a preferential growth towards the trophic factor-releasing capsule. Taken together, these results provide evidence that encapsulated genetically engineered cells are an effective means of long-term trophic factor supply into the adult rat brain and that the delivery of glial cell line-derived neurotrophic factor can sustain dopaminergic graft function and survival.     

The effects of pulmonary rehabilitation combined with inspiratory muscle training on pulmonary function and inspiratory muscle strength in elderly patients with chronic obstructive pulmonary disease]

It has been suggested that pulmonary rehabilitation compined with inspiratory muscle training (IMT) might improve pulmonary function and respiratory muscle strength in elderly patients with chronic obstructive pulmonary disease (COPD). To test this hypothesis, inspiratory muscle strength (PImax), expiratory muscle strength (PEmax) and resting pulmonary function were measured in 13 elderly patients with COPD (aged 70.3 +/- 2.7 years). Inspiratory muscle training (IMT) was performed for 15 min twice a day, using a pressure threshold device, for a total of 12 weeks. The inspiratory threshold was set at 15% of maximal inspiratory pressure (PImax) for each individual. Pulmonary rehabilitation was performed for 12-h sessions over a 12-week period. Patients with COPD were assigned randomly to two groups: pulmonary rehabilitation combined with IMT (group A) (n = 7), and conventional pulmonary rehabilitation only (group B) (n = 6). Functional residual capacity (FRC) decreased significantly from 4.3 +/- 0.4 L at baseline to 3.9 +/- 0.4 L after rehabilitation (p < 0.01), Vp significantly increased from 4.6 +/- 0.8 L/sec at baseline to 5.1 +/- 0.7 L/sec after rehabilitation (p < 0.05) and the PImax increased significantly from 51.5 +/- 5.4 cmH2O at baseline to 80.9 +/- 7.0 cmH2O after rehabilitation (p < 0.02) in group A. However, these variables did not change in group B. There was no improvement in the 10-minutes walking distance of group A, but there was a significant increase in that of group B. It can be concluded that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD.     

The diaphragm and respiratory muscles

A rapid procedure for the purification of the redox-regulated chloroplast fructose-1,6-bisphosphatase [EC 3.1.3.11] from spinach leaf extract to homogeneity is described. No thiol-reducing agents were present during the purification and the enzyme is > 99% in the oxidized form. A rapid procedure to reduce and activate the Fru-1,6-P2ase by dithiothreitol in the absence of thioredoxin is described. Reduction activates the enzyme up to several hundred-fold when assayed at pH 8.0 with 2 mM Mg2+. The activity of the purified oxidized enzyme is unusually sensitive to changes in Mg2+ and H+ concentration. Tenfold changes in Mg2+ or H+ concentration lead to > 100-fold increases in activity. The recoveries of fructose-1,6-bisphosphatase activity as determined by the activity of the oxidized enzyme at pH 8.0/20 mM Mg2+; pH 9.0/2 mM Mg2+; pH 8/2 mM Mg2+ plus 0.1 mM Hg(II) or of the reduced enzyme at pH 8.0/2 mM Mg2+ are similar (approximately 40%) indicating that the major proportion of these activities in a leaf extract is catalyzed by the same enzyme. Moreover, antibodies raised against the purified enzyme inhibit all of the above activities in crude leaf extracts. The kinetic properties of the purified enzyme suggest that the oxidized Mg(2+)-dependent enzyme can play no significant role in photosynthetic carbon assimilation. A survey of some kinetic properties of Fru-1,6-P2ase activity in extracts of various photosynthetic organisms reveals that all 11 species examined possess a redox- and pH/Mg(2+)-stimulated Fru-1,6-P2ase, whereas Fru-1,6-P2ase in extracts of Taxus baccata (a gymnosperm), Chlorella vulgaris (a green alga), and the cyanobacterium Nostoc muscorum were not activated by Hg(II). The heat stability that proved useful in the purification of the spinach enzyme was conserved in both angiosperms and gymnosperms. The oxidized enzyme (which normally has no thiol groups accessible to 5,5'-dithio-bis[2-nitrobenzoic acid]) but not the reduced enzyme can be stimulated many hundred-fold by addition of extraordinarily low concentrations of Hg(II) to a complete assay mixture. With the aid of EDTA as a Hg(II) buffer, half-maximal stimulation was achieved at 2 x 10(-16) M free Hg(II). Methylmercury also stimulates the enzyme many hundred-fold at very low concentrations. The concentration for half-maximal stimulation by methylmercury was determined with a cyanide buffer to be approximately 10(-16) M. This, together with the high affinity of the enzyme for Hg(II), suggests that Hg(II) stimulates the enzyme by binding to an enzyme thiol group that be comes exposed in the catalytically active enzyme, thereby stabilizing the oxidized enzyme in an active conformation. By contrast, in the absence of Fru-1,6-P2 and either Mg2+ or Ca2+, Hg(II) (even at 2 x 10(-16) M) rapidly inactivates the oxidized Fru-1,6-P2ase. This inactivation is similar to the inactivation of Fru-1,6-P2ase that occurred at high pH (> 9) and which is also prevented by Fru-1,6-P2 and either Mg2+ or Ca2+. Although the Hg(II)- and high pH-inactivated oxidized enzyme has no activity, both forms of the enzyme can be activated by reduction. The usefulness of buffers to maintain low, defined Hg(II) and organic mercurial concentrations is discussed.     

Respiratory comfort of automatic tube compensation and inspiratory pressure support in conscious humans

OBJECTIVE: To compare the new mode of ventilatory support, which we call automatic tube compensation (ATC), with inspiratory pressure support (IPS) with respect to perception of respiratory comfort. ATC unloads the resistance of the endotracheal tube (ETT) in inspiration by increasing the airway pressure, and in expiration by decreasing the airway pressure according to the non-linear pressure-flow relationship of the ETT. DESIGN: Prospective randomized single blind cross-over study. SETTING: Laboratory of the Section of Experimental Anaesthesiology (Clinic of Anaesthesiology; University of Freiburg). SUBJECTS: Ten healthy volunteers. INTERVENTIONS: The subjects breathed spontaneously through an ETT of 7.5 mm i.d. Three different ventilatory modes, each with a PEEP of 5 cmH2O, were presented in random order using the Dr?ger Evita 2 ventilator with prototype software: (1) IPS (10 cmH2O, 1 s ramp), (2) inspiratory ATC (ATC-in), (3) inspiratory and expiratory ATC (ATC-in-ex). MEASUREMENTS AND MAIN RESULTS: Immediately following a mode transition, the volunteers answered with a hand sign to show how they perceived the new mode compared with the preceding mode in terms of gain or loss in subjective respiratory comfort: "better", "unchanged" or "worse". Inspiration and expiration were investigated separately analyzing 60 mode transitions each. Flow rates were continuously measured. The transition from IPS to either type of ATC was perceived positively, i.e. as increased comfort, whereas the opposite transition from ATC to IPS was perceived negatively, i.e. as decreased comfort. The transition from ATC-in to ATC-in-ex was perceived positively whereas the opposite mode transition was perceived negatively in expiration only. Tidal volume was 1220 +/- 404 ml during IPS and 1017 +/- 362 ml during ATC. The inspiratory peak flow rate was 959 +/- 78 ml/s during IPS and 1048 +/- 197 ml/s during ATC. CONCLUSIONS: ATC provides an increase in respiratory comfort compared with IPS. The predominant cause for respiratory discomfort in the IPS mode seems to be lung over-inflation.     

Control of abdominal muscles

Abdominal muscles serve many roles; in addition to breathing, especially at higher levels of chemical drive or at increased end-expiratory lung volumes, they are responsible for, or contribute to, such protective reflexes as cough, sneeze, and vomiting, generate the high intra-abdominal pressures necessary for defecation and parturition, are active during postural adjustments, and play an essential role in vocalization in many species. Despite this widespread involvement, however, their control has, with rare exceptions, received little attention for two major reasons. First, in most anesthetized or decerebrate preparations, they are relatively inactive at rest, in part because the position of the preparation (supine or prone with abdomen supported), reduces lung volume and, therefore, their activity. Second, unlike phrenic motoneurons innervating the diaphragm, identification of motoneurons to a particular abdominal muscle is difficult. At the lumbar level, a given motoneuron may innervate any one of the four abdominal muscles; at the thoracic level, they are also intermixed with those innervating the intercostals. The two internal muscles, the internal oblique and the transverse abdominis, respond more to increases in chemical or volume-related drive than the two external muscles, the rectus abdominis and external oblique; the basis for this differential sensitivity is unknown. Segmental reflexes at the thoracic and lumbar levels are sufficient to activate abdominal motoneurons in the absence of descending drive but the basis for these reflex effects is also unknown. Neuroanatomical experiments demonstrate many more inputs to, and outputs from, the nucleus retroambigualis, the brainstem region in which the premotor neurons are located, than can be accounted for by their respiratory role alone. These other connections likely subserve activities other than respiration. Studies of the multifunctional roles of the abdominal muscles, on the basis of recent work, hold considerable promise for improving our understanding of their control.