Biomedical subjects

Stefan Matecki

Publications and source records attributed to Stefan Matecki.

16 recordsLinked to original sources

PubMed2006

Clinical effects of heliox administration for acute bronchiolitis in young infants.

OBJECTIVE: To assess the effect of heliox, a helium-oxygen mixture, on respiratory distress symptoms in young infants. DESIGN: Prospective, randomized, double-blind study. SETTING: Pediatric ICU (PICU) of a university hospital. PATIENTS: Twenty infants, all < 3 months old, admitted to the PICU with moderate-to-severe acute respiratory syncytial virus bronchiolitis. INTERVENTIONS: All infants were randomly and blindly assigned to inhale either heliox or an air-oxygen mixture (airox) for 1 h under an oxyhood. MEASUREMENTS AND RESULTS: After 1 h, the respiratory distress score was significantly lower in the heliox group compared with the airox group (3.05 vs 5.5, p < 0.01), with a significant reduction in accessory muscles use (p < 0.05) and expiratory wheezing (p < 0.01). In contrast, inspiratory breath sounds and cyanosis did not significantly differ between groups. The ex-premature infants of the heliox group had a higher respiratory distress score at baseline compared with the term infants of this group (5.8 vs 5.2, p < 0.05) and a comparable decrease in the score at 60 min. CONCLUSIONS: In young infants, even those born prematurely, heliox breathing induced a rapid reduction in accessory muscles use and expiratory wheezing. Further studies are needed to confirm the decreased respiratory muscle work of breathing during heliox inhalation in this population.

Acute Disease↗

PubMed2005

Effects of short vs. prolonged mechanical ventilation on antioxidant systems in piglet diaphragm.

OBJECTIVE: Prolonged controlled mechanical ventilation (MV) is known to induce diaphragmatic oxidative stress that seems to be an important factor reducing force-generating capacity. To better understand the cellular mechanisms involved, this work examined the effect of short vs. prolonged MV on antioxidant defense in the diaphragm. DESIGN AND SETTING: Prospective, randomized, controlled animal study in a university laboratory. METHODS: Eleven piglets (15-20 kg) were assigned to one of two groups: a long-MV group (n=6) ventilated for 3 days or a short-MV group (n=5) ventilated for 3 h. Force frequency curves of the transdiaphragmatic pressure (Pdi) were obtained in vivo by phrenic nerve pacing. Oxidative stress was evaluated by thiobarbituric reactive substance (TBARs) content and the enzymatic antioxidant activity of both superoxide dismutase (SOD) and glutathione peroxidase (GPx) in samples of diaphragm. RESULTS: Pdi decreased in the long-MV group by 30-35% over the 3 days at all frequencies compared to the short-MV group. Diaphragm TBARs content was significantly higher and SOD activity lower in long-MV animals than in short-MV animals after 72 h. GPx activity tended to be lower in diaphragms from long-MV animals, but this difference was not significant. CONCLUSIONS: This study shows that 3 days of MV in piglets is associated with a decrease in antioxidant activity which could emphasize oxidative stress and both contribute to the diaphragm dysfunction caused by MV.

Animals↗

PubMed2005

Volume-guaranteed pressure-support ventilation facing acute changes in ventilatory demand.

OBJECTIVE: To compare volume support ventilation (VSV) in which the pressure support level is continuously adjusted to deliver a preset tidal volume, with pressure support ventilation (PSV), in terms of patient behavior and ventilator response when ventilatory demand was increased by addition of dead space to the circuit. DESIGN AND SETTING: Randomized cross-over study in an intensive care unit university hospital. INTERVENTIONS: We assessed in ten patients being weaned off mechanical ventilation the effect of increasing the ventilatory demand by adding a heat-and-moisture exchanger to augment the dead space with a fixed level of PSV and VSV. MEASUREMENTS AND RESULTS: Arterial blood gases, breathing pattern, and respiratory effort parameters at the end of each of the four steps. Adding dead space significantly increased minute ventilation and PaCO2 values with both PSV and VSV. Indexes of respiratory effort (pressure-time index of respiratory muscles and work of breathing) increased with both ventilatory modes after dead-space augmentation. This increase was 2.5-4 times with VSV than with PSV and induced overt respiratory distress in two patients. The assistance delivered during VSV decreased significantly after dead-space augmentation, from 15.0+/-6.5 to 9.1+/-4.8 cmH2O, whereas no change occurred with PSV. CONCLUSIONS: With a fixed level of VSV, but not of PSV, an increase in ventilatory demand results in a decrease in the pressure support provided by the ventilator, opposite to the desired response. VSV may conceivably result in respiratory distress in clinical settings.

APACHE↗

PubMed2005

The effect of respiratory muscle training with CO2 breathing on cellular adaptation of mdx mouse diaphragm.

The aim of our study was to investigate the cellular mechanisms induced by hypercapnic stimulation of ventilation, during 6 weeks/30 min per day, in 10 mdx and 8 C57BL10 mice (10+/-0.2 months old). Ten mdx and eight C57BL10 mice served as control group. This respiratory training increases in vitro maximal tetanic tension of the diaphragm only in mdx mice. Western blot analysis of diaphragm showed: (1) an over-expression of alpha-dystrobrevin in mdx and C57BL10 training group compared to control group (8100+/-710 versus 6100+/-520 and 2800+/-400 versus 2200+/-250 arbitrary units); (2) a decrease in utrophin expression only in mdx training group compared to control group (2100+/-320 versus 3100+/-125 arbitrary units). Daily respiratory muscle training in mdx mice, induces a beneficial effect on diaphragm strength, with an over-expression of alpha-dystrobrevin. Further studies are needed to determine if, in absence of dystrophin, the over-expression of alpha-dystrobrevin could be interpreted as a possible pathway to improve function of dystrophic muscle.

Adaptation, Physiological↗

PubMed2005

Changes in respiratory muscle endurance during puberty.

The evaluation of respiratory muscle endurance provides clinically useful information on muscle function, especially in children with respiratory and neuromuscular diseases. However, endurance may be lower in young children than in older children because of the major physical changes of puberty. We thus compared respiratory muscle endurance in 15 healthy pre- and peripubertal children (S1-S2/P1 group) and 14 healthy children near the end of the pubertal process (S4P4 group). All performed a respiratory muscle endurance test threshold load fixed at 50% of the individual maximal inspiratory pressure; (Pi(max)), using a standardized method with a controlled breathing pattern. No significant difference was found between groups for Pi(max). The mean endurance time limit for the S1-S2/P1 group was 138 +/- 20 sec. The S4P4 group was able to breathe with the threshold valve for more than 20 min (1,200 sec) without task failure, except for one girl (385 sec). This study shows that inspiratory muscle endurance is significantly lower in children in early puberty compared to children at the end of the pubertal process. If the underlying mechanisms are not well-known, the present study revealed that if we use the same inspiratory load in prepubertal children as in adults during clinical testing, we are likely to underestimate the susceptibility to task failure of their respiratory muscles. To define a fatigue threshold for the respiratory muscles, as a function of age, thus appears clinically important in further studies, particularly for the management of children with respiratory diseases.

Adolescent↗

PubMed2005

Optimization of regional intraarterial naked DNA-mediated transgene delivery to skeletal muscles in a large animal model.

Effective gene therapy for muscular dystrophy will likely require intravascular administration. Although plasmid DNA (pDNA) contained within a large volume and rapidly infused into a major artery can achieve gene transfer within downstream muscles, this is associated with substantial muscle edema. Here we hypothesized that excessive edema-related increases in intramuscular pressure (IM pressure) developed during intraarterial pDNA injections could hinder successful gene delivery. Accordingly, we monitored IM pressure during injection of pDNA carrying a LacZ transgene into the femoral artery of rats and pigs. Large variations in IM pressure were found between different muscles. There was a significant inverse relationship between IM pressure and the subsequent level of gene transfer to muscle. Modification of the injection protocol to reduce IM pressure led to greatly increased pDNA-mediated gene expression and reduced muscle damage in pigs. Under the most optimized conditions, average transfection within eight different muscles of the pig hind limb amounted to 22% of all fibers, attaining a maximum of 60% in the gastrocnemius muscle. We conclude that IM pressure monitoring is a simple and useful procedure, which can be applied in both small and large animals to help optimize pDNA-mediated gene transfer to skeletal muscles by the intraarterial route.

Animals↗

PubMed2004

Regenerative capacity of the dystrophic (mdx) diaphragm after induced injury.

Duchenne muscular dystrophy is characterized by myofiber necrosis, muscle replacement by connective tissue, and crippling weakness. Although the mdx mouse also lacks dystrophin, most muscles show little myofiber loss or functional impairment. An exception is the mdx diaphragm, which is phenotypically similar to the human disease. Here we tested the hypothesis that the mdx diaphragm has a defective regenerative response to necrotic injury, which could account for its severe phenotype. Massive necrosis was induced in mdx and wild-type (C57BL10) mouse diaphragms in vivo by topical application of notexin, which destroys mature myofibers while leaving myogenic precursor satellite cells intact. At 4 h after acute exposure to notexin, >90% of diaphragm myofibers in both wild-type and mdx mice demonstrated pathological sarcolemmal leakiness, and there was a complete loss of isometric force-generating capacity. Both groups of mice showed strong expression of embryonic myosin within the diaphragm at 5 days, which was largely extinguished by 20 days after injury. At 60 days postinjury, wild-type diaphragms exhibited a persistent loss ( approximately 25%) of isometric force-generating capacity, associated with a trend toward increased connective tissue infiltration. In contrast, mdx diaphragms achieved complete functional recovery of force generation to noninjured values, and there was no increase in muscle connective tissue over baseline. These data argue against any loss of intrinsic regenerative capacity within the mdx diaphragm, despite characteristic features of major dystrophic pathology being present. Our findings support the concept that significant latent regenerative capacity resides within dystrophic muscles, which could potentially be exploited for therapeutic purposes.

Animals↗

PubMed2004

Therapeutic gene transfer to dystrophic diaphragm by an adenoviral vector deleted of all viral genes.

Duchenne muscular dystrophy is caused by defects in the dystrophin gene, and the mdx mouse is the most frequently employed genetic model of this disease. It is well known that different muscle groups do not respond in the same way to dystrophin deficiency. In particular, the mdx mouse diaphragm exhibits severe morphological and functional changes not found in other mdx muscles. Use of early generation adenoviral vectors to deliver genes to the diaphragm in immunocompetent mdx mice has been associated with substantial functional toxicity and a rapid loss of transgene expression. Here we determined the response to dystrophin gene replacement in the mdx diaphragm using a "gutted" adenoviral vector that contains the coding sequence of two full-length dystrophin genes and is deleted of most viral DNA sequences. At 1 wk postdelivery of the vector, 23.6 +/- 4% of total fibers in the injected diaphragm bundle expressed dystrophin at the sarcolemma, which remained stable over the study duration of 30 days without the need for continuous immunosuppression. Treated diaphragms showed a significantly improved resistance to the abnormal force deficits induced by high-stress muscle contractions, the latter being a functional hallmark of dystrophin-deficient muscle. This functional amelioration was achieved despite the presence of mildly increased inflammation (CD4+ and CD8+ lymphocytes) within the vector-treated diaphragms. To our knowledge, this is the first demonstration that a viral vector can achieve reversal of functional abnormalities in the dystrophic diaphragm via therapeutic dystrophin gene transfer without the need for sustained immunosuppressive therapy.

Adenoviridae↗

PubMed2004

Sustained improvement of muscle function one year after full-length dystrophin gene transfer into mdx mice by a gutted helper-dependent adenoviral vector.

Dystrophin gene transfer using helper-dependent adenoviral vectors (HDAd) deleted of all viral genes is a promising option to treat muscles in Duchenne muscular dystrophy (DMD). Previously, we reported high-level dystrophin expression and functional correction of dystrophin-deficient (mdx) mouse muscle 60 days after gene transfer with an HDAd encoding two full-length murine dystrophin cDNAs (referred to as HDCBDysM). In the present study, we tested the long-term efficacy of HDCBDysM by examining muscle contractility parameters and the stability of dystrophin expression 1 year after injection into neonatal mdx muscles. At this point, HDCBDysM-treated muscles averaged 52% dystrophin-positive fibers. Treated muscles also displayed significantly greater isometric force production as well as greater resistance to the force deficits and damage caused by eccentric contractions. The level of protection against eccentric contraction-induced force deficits correlated with the percentage of dystrophin-positive fibers. Furthermore, HDCBDysM treatment restored the dystrophin-glycoprotein complex (DGC) to the sarcolemma and improved other aspects of mdx muscle histopathology examined (central nucleation, muscle hypertrophy, and mononuclear [phagocytic] cell infiltration). These improvements occurred despite the induction of a humoral response against murine dystrophin. Our results indicate that major therapeutic benefits of HDCBDysM are maintained for a long period of the animals' lifespan and suggest that HDCBDys holds promise for treating DMD by gene therapy.

Adenoviridae↗

PubMed2003

Preferential diaphragmatic weakness during sustained Pseudomonas aeruginosa lung infection.

Infection with Pseudomonas aeruginosa plays a major role in the pulmonary inflammation and injury associated with cystic fibrosis. Lung inflammation may also lead to more widespread systemic effects on other organs. We tested the following hypotheses: (1) ongoing P. aeruginosa lung infection produces diaphragmatic and limb muscle weakness and (2) such muscle dysfunction is directly correlated with the level of pulmonary inflammation. Chronic bronchopulmonary infection with mucoid P. aeruginosa was induced in C57BL/6 mice. At Day 2 after infection, diaphragmatic force was decreased (37%) only in mice infected with a high dose of 1 x 10(6) cfu, whereas by Day 7 after infection, diaphragmatic force was similarly reduced (36%) even at a fivefold lower inoculating dose. No significant correlations were found between diaphragmatic weakness and pulmonary inflammation, as assessed by the number of neutrophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid. Moreover, in marked contrast to the diaphragm, no effects of P. aeruginosa infection on contractile function were observed in prototypical slow- and fast-twitch hindlimb muscles. We conclude that sustained lung infection with P. aeruginosa induces preferential weakness of the diaphragm, which is not directly correlated with the degree of pulmonary inflammation induced under these conditions.

Animals↗

PubMed2003

Respiratory pressures in boys from 11-17 years old: a semilongitudinal study.

We hypothesized that in children, maximal respiratory pressures increase with age and more during the pubertal growth spurt. The aim of this work was to follow maximal respiratory pressures, with a semilongitudinal study, in three groups of prepubertal, peripubertal, and postpubertal children in order to specify pressure changes with age and determine the contributions of growth and puberty. A semilongitudinal study was conducted in 44 boys assigned to three overlapping age groups: from 11-13 (prepubertal stage), from 13-15 (pubertal stage), and from 15-17 years (postpubertal stage). The children underwent annual testing for maximal respiratory pressures and spirometric values. Body mass, height, lean body mass assessed from four skinfold thicknesses, and stage of development were also evaluated. Maximal respiratory pressure increased significantly with growth from 11-17 years for maximal inspiratory pressure, and from 11-15 years for maximal expiratory pressure. We observed an increase in the slope of the regression lines between age and lean body mass during the pubertal growth spurt, without an increase in the slopes of the regression lines between age and respiratory pressures. In conclusion, the relationships between age and respiratory pressures are not modified by the growth spurt, indicating that anthropometric characteristics have little role in determining respiratory pressures.

Adolescent↗

PubMed2002

Post-extubation stridor in intensive care unit patients. Risk factors evaluation and importance of the cuff-leak test.

OBJECTIVE: To evaluate the incidence and identify factors associated with the occurrence of post-extubation stridor and to evaluate the performance of the cuff-leak test in detecting this complication. DESIGN: Prospective, clinical investigation. SETTING: Intensive care unit of a university hospital. PATIENTS: Hundred twelve extubations were analyzed in 112 patients during a 14-month period. INTERVENTION: A cuff-leak test before each extubation. MEASUREMENTS AND RESULTS: The incidence of stridor was 12%. When we chose the thresholds of 130 ml and 12% to quantify the cuff-leak volume, the sensitivity and the specificity of the test were, respectively, 85% and 95%. The patients who developed stridor had a cuff leak significantly lower than the others, expressed in absolute values (372+/-170 vs 59+/-92 ml, p<0.001) or in relative values (56+/-20 vs 9+/-13%, p<0.001). Stridor was associated with an elevated Simplified Acute Physiology Score (SAPS II), a medical reason for admission, a traumatic or difficult intubation, a history of self-extubation, an over-inflated balloon cuff at admission to ICU and a prolonged period of intubation. These results provide a framework with which to identify patients at risk of developing a stridor after extubation. CONCLUSION: A low cuff-leak volume (<130 ml or 12%) around the endotracheal tube prior to extubation is useful in identifying patients at risk for post-extubation stridor.

Airway Obstruction↗

PubMed2002

Effects of prolonged mechanical ventilation on respiratory muscle ultrastructure and mitochondrial respiration in rabbits.

OBJECTIVE: To investigate in rabbits whether prolonged mechanical ventilation (PMV) leads to ultrastructural changes in respiratory muscles and alters diaphragm mitochondrial respiration. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: We studied respiratory muscles of seven rabbits after 49+/-1 h of controlled mechanical ventilation. Ten nonventilated rabbits were used as a control group. MEASUREMENTS AND RESULTS: After mechanical ventilation electron-microscopic observations of the diaphragm and the external intercostal muscles revealed disrupted myofibrils, increased number of lipid vacuoles in the sarcoplasm, and smaller mitochondria with focal membrane disruptions. Volumetric and numerical densities of the mitochondria were significantly lower in the PMV group than the control group. Mitochondrial respiration was quantified in isolated diaphragm muscle-cell mitochondria using two respiratory substrates. There was no difference in oxygen consumption values in the three states of mitochondrial respiration between the two groups except for state 2 (basal state) with pyruvate/malate parameter (53.5+/-20 for the ventilated group vs. 33.8+/-10.2 nmol atom O/mg per minute for the control group). There was no significant difference between groups in ADP/O ratio or respiratory control ratio. CONCLUSIONS: PMV leads to respiratory muscle cell degeneration and minor changes in oxidative phosphorylation coupling in diaphragmatic mitochondria. These phenomena may mediate part of damage of respiratory muscles after inactivity related to PMV.

Animals↗

PubMed2002

Comparison of the effects of heat and moisture exchangers and heated humidifiers on ventilation and gas exchange during non-invasive ventilation.

OBJECTIVE: To compare the short-term effects of a heat and moisture exchanger (HME) and a heated humidifier (HH) during non-invasive ventilation (NIV). DESIGN: Prospective, clinical investigation. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-four patients with acute respiratory failure (ARF). INTERVENTION: Each patient was studied with a HME and a HH in a random order during two consecutive 20min periods of NIV. MEASUREMENTS AND RESULTS: Respiratory rate (RR), expiratory tidal volume (VTe) and expiratory minute ventilation (VE) were measured during the last 5 min of each period and blood gases were measured. Mean pressure support and positive end-expiratory pressure levels were, respectively, 15+/-4 and 6+/-2 cmH(2)O. VE was significantly greater with HME than with HH (14.8+/-4.8 vs 13.2+/-4.3 l/min; p<0.001). This increase in VE was the result of a greater RR for HME than for HH (26.5+/-10.6 vs 24.1+/-9.8 breaths/min; p=0.002), whereas the VT for HME was similar to that for HH (674+/-156 vs 643+/-148 ml; p=0.09). Arterial partial pressure of carbon dioxide (PaCO(2)) was significantly higher with a HME than with a HH (43.4+/-8.9 vs 40.8+/-8.2 mmHg; p<0.005), without significantly changing oxygenation. CONCLUSION: During NIV the increased dead space of a HME can negatively affect ventilatory function and gas exchange. The effect of HME dead space may decrease efficiency of NIV in patients with ARF.

Acute Disease↗

PubMed2002

Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy.

The aim of this study was to evaluate the effects of low intensity, home inspiratory muscle training on respiratory muscle endurance in children with Duchenne muscular dystrophy, using a double-blind protocol. The originality aspect of this study is the use of a reproducible method of endurance and of the same method for evaluation and training. We studied eight trained children (mean age 14.7+/-4.5 years) and eight control children (mean age, 12.6+/-1.8 years). For 6 weeks, children breathed twice a day for 10 min through a valve with either 30% (training group) or less than 5% (control group) of their maximum inspiratory pressure (P(imax)). The results showed (1) a 46% improvement in the time limit after training in the training group and no change in the control group and (2) a significant correlation between the total time of respiratory muscle training and the percentage of endurance improvement in the training group. We conclude that specific training improves respiratory muscle endurance in Duchenne muscular dystrophy and the effectiveness of training appears to be dependent on the quantity of training.

Adolescent↗

PubMed2002

Effect of prolonged undernutrition on rat diaphragm mitochondrial respiration.

Previous studies have shown that undernutrition induces an impairment of the respiratory muscle function in patients with chronic lung disease. To explain this, we hypothesized that undernutrition could decrease oxidative metabolism in the diaphragm. We therefore examined the effect of prolonged undernutrition on diaphragm mitochondrial oxygen uptake with pyruvate and palmitate as substrates in adult rats. Ten rats served as controls (CTL). Ten nutritionally deprived rats (ND) received 40% of their estimated daily nutrition. Five weeks of undernutrition induced a 33% decrease in state 3 respiration with pyruvate plus malate as substrate (993 +/- 171 versus 1488 +/- 167 nmol atomic O/mg/min, P < 0.01) and a 39% decrease with palmitate plus malate (516 +/- 89 versus 850 +/- 165 nmol atomic O/mg/min, P < 0.05). With succinate plus rotenone, there was no significant difference in the respiratory rate between groups. In the ND group, we found a significant decrease in citrate synthase activity (P < 0.01), and also in reduced nicotinamine adenine dinucleotide (NADH) dehydrogenase activity (P < 0.05), which cannot alone induce such a state 3 respiratory decrease. This showed that undernutrition in rat diaphragm does not induce an alteration in protein complexes I, II, III, and IV, or the F complex containing the mitochondrial ATPase of the electron transport chain. In conclusion, the main result of this study was that prolonged undernutrition induced a decrease in mitochondrial respiration secondary to a significant reduction in NADH generation by the Krebs cycle, which may affect respiratory muscle function with implications for patient care.

Animal Nutritional Physiological Phenomena↗