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Expiratory patterns during sleep in normal full-term and premature neonates.

Airflow (V), tidal volume (TV), and EEG polygraphic recordings were performed in 30 normal full-term newborns (FTN) and in 10 premature newborns (PN). Besides the classical expiratory flow (CEF), a retarded expiratory flow (REF) was observed: a phase of slow flow ending with a sharp increase. REF was mostly encountered in quiet sleep (QS) in FTN. During REF, Te and Ttot became longer; Ti became shorter, with an increase in TV. In QS, sighs were more numerous in FTN with a high percentage of REF. Expiratory sudden short arrests of airflow (SSAA), less than or equal to 2 s, during expiration were more frequent in active sleep (AS) in FTN. REF may be due to some obstruction or to postinspiratory diaphragmatic activity; variations in functional capacity may also be involved.

Electroencephalography↗

Down-regulation of thyroid transcription factor-1 gene expression in fetal lung hypoplasia is restored by glucocorticoids.

The thyroid transcription factor (TTF)-1 has an essential role in lung morphogenesis and development. It is involved in the transcription of surfactant proteins (SP), which are critical in respiratory function. Neonates with congenital diaphragmatic hernia die of respiratory failure caused by pulmonary hypoplasia with associated biochemical immaturity. To gain new insights into the causes of this disorder and the effect of prenatal hormonal treatment on reducing mortality in these infants, we evaluated the expression of TTF-1 as marker of lung morphogenesis and SP-B as marker of lung maturity. Using a rat model of lung immaturity, we show that TTF-1 and SP-B messenger RNA (mRNA) levels are drastically reduced in congenital lung hypoplasia. Interestingly, prenatal dexamethasone (Dex) treatment increased both TTF-1 and SP-B mRNAs over control levels when administered to rats with lung hypoplasia, but it had no effect on TTF-1 or a moderate effect on SP-B mRNA when administered to control rats. TRH alone also increases TTF-1 and SP-B mRNA levels but to a lesser extent than Dex. When administered together with Dex, TRH counteracts the induction observed with the glucocorticoid. The decrease in TTF-1 mRNA levels in lung hypoplasia is paralleled by a down-regulation of TTF-1 protein levels, as well as by a decrease in the TTF-1/DNA complex when the TTF-1-binding site of the SP-B promoter was used as a probe. Both parameters were reestablished after glucocorticoid treatment. Moreover, the regulation of TTF-1 gene expression described in this report is accompanied by the same regulation in its promoter activity, as demonstrated in transfection experiments performed in H-441 human lung-derived adenocarcinoma cells. In conclusion, our data demonstrate, for the first time, that lung hypoplasia and the associated respiratory dysfunction caused by SP-B deficiency are caused, in part, by down-regulation of TTF-1 gene expression. The observations that prenatal glucocorticoid treatment induces the expression of TTF-1 supports routine in utero glucocorticoid treatment of patients expected to have lung hypoplasia.

Adenocarcinoma↗

Bilateral diaphragmatic paralysis following topical cardiac hypothermia.

Topical cardiac hypothermia has been shown to be a safe and effective means of providing protection for the ischemic myocardium during aortic cross-clamping. We report herein two cases of postoperative bilateral diaphragmatic paralysis which we believe resulted from hypothermic injury to the phrenic nerves. After open-heart surgery, both patients experienced prolonged weaning from assisted ventilation and severe orthopnea. Return of normal diaphragmatic and phrenic nerve function was demonstrated in one patient ten months after surgery. Failure to correctly interpret the respiratory failure and orthopnea led to confusion and erroneous types of therapy. Awareness of this complication should lead to improved care and postoperative management of patients.

Adult↗

[Expression of mRNA and protein of ubiquitin in diaphragmatic muscle in burned rats with sepsis in early stage].

OBJECTIVE: To study the expressions of mRNA and protein of ubiquitin in diaphragmatic muscle in burned rats with sepsis. METHODS: The model of burn sepsis was replicated by subjecting the rats to 30 percent total body surface area (TBSA) III degree burn followed immediately by administration of endotoxin (6 mg/kg) into the peritoneal cavity. The rats were randomly divided into 2-and 6-hour groups and a normal control group, with 9 rats in each group. The expressions of ubiquitin mRNA in the diaphragmatic muscle was determined with Northern blot analysis. The expressions of ubiquitin protein in the diaphragmatic muscle were assayed with immunohistochemical method. RESULTS: The expressions of the ubiquitin mRNA (2.4 kb and 1.2 kb) in diaphragmatic muscle of burn rats with sepsis were significantly higher than that of normal control group, especially the 2.4 kb stripe (all P<0.01). A notable increase in the expressions of the ubiquitin mRNA was found in the 6-hour group compared with the 2-hour group (all P<0.01). The expressions of the ubiquitin protein in diaphragmatic muscle of burn rats with sepsis were significantly increased after injury compared with the normal control group. CONCLUSION: The expressions of mRNA and protein of ubiquitin in diaphragmatic muscle are continuously increased soon after injury, suggesting that the protein degradation rate is increased in burn with sepsis. The finding is helpful in the study of the change in metabolism of diaphragmatic muscle and respiratory function.

Animals↗

The effect of anesthesia and surgery on diaphragmatic lymph vessel flow after endotoxin in sheep.

Increases in diaphragmatic lymph vessel flow (Qdi) may be important in preventing ascites because diaphragmatic lymph vessels drain the peritoneal space. However, lymphatic vessel function may be depressed in anesthetized, open chested animals. To test this hypothesis, we cannulated diaphragmatic lymph vessels in five sheep which were anesthetized with 1-2% halothane. We performed a thoracotomy and cannulated a diaphragmatic lymph vessel in each sheep. Then we infused 0.75-1.0 micrograms/kg of E. coli endotoxin intravenously and we measured Qdi and the lymph protein concentration for 2-4 hrs. The data were compared to previously reported data for five unanesthetized sheep (J. Appl. Physiol. 62:706-710, 1987). At baseline Qdi = 0.8 +/- 0.7 (SD) in the anesthetized sheep and 1.0 +/- 0.8 ml/hr in the unanesthetized sheep. After endotoxin, Qdi increased to 4.5 +/- 3.1 ml/hr in the unanesthetized sheep (p less than 0.05) but Qdi did not change in the anesthetized sheep. However, the lymph protein concentration increased similarly in each group, indicating that endotoxin caused the same degree of injury in each group. Our results indicate that diaphragmatic lymph vessel function is depressed in anesthetized, open chested sheep.

Analysis of Variance↗

[Functionally satisfying reconstruction of a combined abdominal, chest wall and diaphragmatic defect with corium following sternum tumor resection].

In a patient, suffering from a chondrosarcoma in the lower sternum, and having undergone radical tumor resection, we had to reconstruct the thoracic wall, the abdominal wall, and the diaphragm. This was done with autologous corium. We report on the advantages of this material and at the same time refer to that of a complete physiologic reconstruction of the diaphragmatic dome seems impossible if accompanied by defects of the thorax and the abdominal wall. Fitting a corset appears necessary as an external support.

Abdominal Muscles↗

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

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

Adult↗

Unilateral agenesis of the diaphragm.

During a period of 4 1/2 years, 37 infants with congenital diaphragmatic hernia were treated. The overall survival rate was 68%. Survival depended more on cardiopulmonary function than the size of the diaphragmatic defect. There was little evidence that infants with agenesis of the diaphragm formed a special group with a poor prognosis, and four of the ten patients with unilateral agenesis survived. A Dacron prosthesis is recommended as a substitute for the missing diaphragm.

Diaphragm↗

Diaphragmatic thickness-lung volume relationship in vivo.

To characterize the relationship of changes in diaphragmatic thickness during contraction to changes in lung volume, we developed a technique to measure diaphragm thickness based on M-mode ultrasonography. First, diaphragmatic thickness was measured in situ at necropsy with ultrasound and verified by measuring the same resected segment of diaphragm by ruler (correlation coefficient = 0.93, slope = 0.97). The technique of imaging the diaphragm in living subjects was developed by using a 15-MHz transducer coupled to an M-mode echocardiograph. Ten normal male volunteers were studied while sitting. The ultrasound transducer was held between the ribs in the ninth lateral interspace, and tidal volume was measured by spirometry. The thickening fraction (TF) was calculated as TF = (thickness at peak inspiration - thickness at end expiration)/thickness at end expiration for each of a series of different sized breaths. The function, TF vs. lung volume, for a range of volumes was linear for each subject and had intrasubject reproducibility with intersubject variability. We conclude that diaphragmatic TF is related to function as determined by lung volume, and this may prove to be a useful technique for in vivo studies of diaphragmatic function.

Diaphragm↗

Demonstrating the effect of theophylline treatment on diaphragmatic movement in chronic obstructive pulmonary disease patients by MR-fluoroscopy.

INTRODUCTION: The purpose of this study was to determine the increase in diaphragmatic excursion of patients with chronic obstructive pulmonary disease (COPD) treated with theophylline by MR-fluoroscopy which is an innovative method to demonstrate effectiveness of this treatment. MATERIALS AND METHODS: Investigations were performed on a 0.3 T open MR unit. MR-fluoroscopy images of 30 patients with COPD were obtained before and after theophylline treatment. Diaphragmatic movement values were recorded for evaluation. RESULTS: The response of the diaphragmatic movement in COPD patients treated with theophylline was evaluated by MR-fluoroscopy and an increase of 48% in diaphragmatic contractility was determined after the treatment. The increase in contractility was found to be parallel with respiratory function tests and clinical status. CONCLUSION: Diaphragmatic movement and response to the medical therapy in patients with COPD can be evaluated by MR-fluoroscopy method which can allow accurate measurements.

Adult↗

Optimal diaphragmatic blood perfusion.

The intrabreath time course of phrenic artery blood perfusion (Qpha) was studied in five anesthetized dogs. The diaphragm was paced with submaximal levels of stimulation at various duty cycles (DC) to achieve tension-time index below and above the fatigue threshold (0.03-0.60). Left Qpha was measured via Doppler technique during control (inactive diaphragm) and during two submaximal levels of bilateral phrenic nerve stimulation sustained for 1 min. Measurements were done when Qpha reached steady state in each run. The frequency of pacing of each run was 10/min, and the DC ranged from 0.1 to 0.9 in 0.1 increments. Shortening of costal and crural segments was measured by sonomicrometry. It was found that Qpha during the diaphragmatic contraction phase (QphaC) was a sigmoidal function of DC and was not affected by the levels of transdiaphragmatic pressure (Pdi) explored (34-64% of maximal Pdi). Qpha during the diaphragmatic relaxation phase (QphaR) was a parabolic function of the DC, reaching an optimal value at DC of approximately 0.3 at any given Pdi. QphaR increased significantly with the preceding level of Pdi. QphaT (the sum of QphaC and QphaR) was a parabolic function of DC, reaching peak values at DC of 0.4-0.6 and then decreasing. This function was similar at two levels of Pdi. Post-pacing hyperemia was directly related to tension-time index greater than 0.20.

Animals↗

Contributions of changing rib cage--diaphragm interactions to the ventilatory depression of halothane anesthesia.

The ventilatory response to CO2 was subdivided into that portion due to increasing rib cage expansion, and that due to increased diaphragmatic descent. Five children were studied, awake, and anesthetized with halothane, 0.8-0.9%. During anesthesia there was a 67+/-8% reduction (mean+/-SE) in the slope of the response of overall ventilation to an increase in CO2. This was primarily due to an 89+/-8% reduction in the recruitment of rib cage ventilation (P less than .001). There was no significant change in the slope of the diaphragmatic response (anesthetized value 19+/-21% less than control), although the response curve was shifted to the right so that a higher CO2 concentration was needed to stimulate a given level of diaphragmatic excursion. Additional measurements of the inspiratory intercostal electromyogram in three adult subjects documented a rapid, profound depression of intercostal activity with halothane anesthesia that was associated with a marked decrease in rib cage ventilation. The authors conclude that a major component of the ventilatory depression associated with halothane anesthesia results from the preferential suppression of intercostal muscle function with relative sparing of diaphragmatic activity.

Adolescent↗

[Quantitative study of a SEM image processing system on the absorptive mesothelium of the diaphragmatic peritoneum].

SEM and a medical image processing system attached to SEM were used to study the peritoneal mesothelium on mice diaphragm. The absorptive mesothelium was first reported owing to its function and morphology. The absorptivity of diaphragmatic peritoneum was surveyed by the measurement of the area of the absorptive mesothelium. The arrangement of the absorptive mesothelium on diaphragmatic peritoneum was block-like with abnormal distribution, and the maximum and minimum areas of the block were 1153 microns 2 and 66 microns 2. But the absorptive mesothelium on left and right half diaphragm were normally distributed. The average areas of the absorptive mesothelium on all diaphragm, left half diaphragm and right half diaphragm were 432.6 microns 2, 270.5 microns 2 and 512.0 microns 2 respectively. The distributive law of the absorptive mesothelium was costal portion > sternum portion > vertebral column portion. The average absorptivity of all diaphragmatic peritoneum was 29.2%, but that of left and right half diaphragmatic peritoneum were 17.4% and 32.9% respectively.

Absorption↗

Assist-control mechanical ventilation attenuates ventilator-induced diaphragmatic dysfunction.

Controlled mechanical ventilation induced a profound diaphragm muscle dysfunction and atrophy. The effects of diaphragmatic contractions with assisted mechanical ventilation on diaphragmatic isometric, isotonic contractile properties, or the expression of muscle atrophy factor-box (MAF-box), the gene responsible for muscle atrophy, are unknown. We hypothesize that assisted mechanical ventilation will preserve diaphragmatic force and prevent overexpression of MAF-box. Studying sedated rabbits randomized equally into control animals, those with 3 days of assisted ventilation, and those with controlled ventilation, we assessed in vitro diaphragmatic isometric and isotonic contractile function. The concentrations of contractile proteins, myosin heavy chain isoform, and MAF-box mRNA were measured. Tetanic force decreased by 14% with assisted ventilation and 48% with controlled ventilation. Maximum shortening velocity tended to increase with controlled compared with assisted ventilation and control. Peak power output decreased 20% with assisted ventilation and 41% with controlled ventilation. Contractile proteins were unchanged with either modes of ventilation; myosin heavy chain 2X mRNA tended to increase and that of 2A to decrease with controlled ventilation. MAF-box gene was overexpressed with controlled ventilation. We conclude that preserving diaphragmatic contractions during mechanical ventilation attenuates the force loss induced by complete inactivity and maintains MAF-box gene expression in control.

Actins↗