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PubMed1993

Inhibition of natural killer cell activity by therapeutic levels of theophylline.

Theophylline, as used for the treatment of asthma and chronic obstructive pulmonary disease, may have several effects, including direct bronchodilation, improvement in diaphragmatic and ciliary function, and possibly immune modulation. In this study, we quantified the capacity for theophylline to inhibit natural killer (NK) cells and investigated the mechanism(s) that mediate this inhibition. Theophylline at 10 micrograms/ml and 20 micrograms/ml inhibited the tumoricidal activity of isolated peripheral blood lymphocytes (PBL) by 19 +/- 5% and 36 +/- 6%, respectively (n = 6). Using fluorescence-activated cell sorting, we purified NK cells from PBL and tested theophylline's effects on the kinetics of tumor lysis (Vmax) and on tumor binding. Theophylline at 20 micrograms/ml reduced Vmax by 40 +/- 9% but had no effect on tumor binding. We compared the effects of theophylline, which is both a phosphodiesterase (PDE) inhibitor and an adenosine receptor (AdR) antagonist, with agents that range from relatively pure AdR antagonists to pure PDE inhibitors. Inhibition of NK activity occurred only with PDE inhibitors. We also extracted lymphocyte PDE and observed a direct correlation (r2 = 0.99) between theophylline's activity as a PDE inhibitor and its capacity to inhibit NK activity. These results suggest that theophylline inhibits NK cytotoxicity through its activity as a PDE inhibitor. The clinical relevance of these findings awaits further study.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Development in lung function of the affected side after repair of congenital diaphragmatic hernia.

The widespread use of newly developed techniques including extracorporeal membrane oxygenation (ECMO) has led to the survival of a number of patients with congenital diaphragmatic hernia (CDH) and associated hypoplastic lung. However, it is not fully recognized whether the hypoplastic and small lung of the affected side has the ability to develop its function after repair of CDH. The authors studied the lung function of 32 patients with CDH in whom these new methods were used. Two parameters, lung volume and pulmonary perfusion amount, were used to evaluate lung function. The former (checked by computed tomography scan) was used to evaluate the size of lung; the latter (checked by perfusion scintigram) was used to assess vascular density. The patients were divided into two groups, based on values of alveolar-arterial difference in oxygen content (AaDo2) at the time of admission. In group A (AaDo2 < 500 mm Hg; 12 cases), whose respiratory distress was mild and could be managed with ventilator care alone, the mean lung volume value for the affected side was 86% of the contralateral lung value from the initial study, and reached 93% at the time of follow-up study. The perfusion amount also exceeded 80% of the contralateral lung value from the initial study. Thus, it is likely that group A's affected-side lung is not small and has developed at a rate similar to that of the contralateral lung. However, in group B patients (AaDo2 > 500 mm Hg; 20 cases), who had severe respiratory distress at the admission and were managed with new techniques including ECMO, both lung volume and perfusion amount of the affected side initially were low in all cases (ie, mean values were 61% and 53% of contralateral-lung values, respectively). At the time of follow-up, the lung volume had increased in most cases (mean value, 88% of the contralateral lung value), but the perfusion amount of the affected side had not increased in most cases. It remained low, or decreased to below the initial value; the mean was 53% of the contralateral lung value. The initial mean perfusion: volume ratio (87%) had decreased significantly (to 62%) by the time of follow-up. This tendency was exaggerated in the 11 ECMO cases. These data might indicate that in most group B cases, the lung of the affected side has little ability to develop arterial branches, or certainly will be delayed in comparison to the contralateral lung, and that enlargement of lung volume may depend on overexpansion or emphysematous change rather than cellular growth. The present data also suggest that, in group B cases, total lung function will depend on the contralateral lung for a relatively long time.

Child↗
PubMed1990

Anatomic and functional abnormalities of the esophagus in infants surviving congenital diaphragmatic hernia.

As more infants with congenital diaphragmatic hernia (CDH) survive by means of extracorporeal membrane oxygenation (ECMO), new clinical observations are being made. We report anatomic and functional abnormalities of the esophagus in these infants. Twenty-two of 30 infants with CDH survived. Three of 7 non-ECMO-treated infants and 14 of 17 ECMO-treated infants had an air- or fluid-filled mediastinal mass that was confirmed by an upper gastrointestinal series as ectatic esophagus. Contrast studies demonstrated severe gastroesophageal reflux. Intra-esophageal pH monitoring confirmed significant reflux (Euler scores greater than 50) in 69% of tested patients. Prolonged acid clearance in most patients implied abnormal peristalsis. Hydramnios was correlated to the observed esophageal abnormalities, being present in 13 of 16 infants with an available amniotic history. All patients had symptomatic gastroesophageal reflux managed without antireflux surgery and were discharged 36 +/- 2 days after initiation of feeding. Follow-up (range: 7 to 56 months; mean: 32 months) showed that weight gain in affected children was slower than in those not affected. All but one are asymptomatic. Repeat upper gastrointestinal series shows persistent ectasia but less gastro-esophageal reflux. Gastroesophageal reflux/ectasia is a new observation with CDH. The associated hydramnios may result from proximal foregut obstruction by kinking the gastroesophageal junction with CDH. The radiographic appearance can be quite unusual. Clinical manifestations of gastro-esophageal reflux are manageable without surgery but may account for the observed compromised growth.

Dilatation, Pathologic↗
PubMed1977

Inhibition of bipolar demand pacemaker by diaphragmatic myopotentials.

This report describes inhibition of a normally functioning bipolar demand pulse generator by diaphragmatic myopotentials. Transient pacemaker suppression occurred repeatedly with deep respiration, straining, the Valsalva maneuver, coughing, sneezing and laughing. When the magnet was applied, none of these maneuvers inhibited the pacemaker. Extensive investigations ruled out an intermittent electrode problem such as a wire fracture or insulation break. Sensing of diaphragmatic myopotentials should be considered in the differential diagnosis of unexplained pacemaker pauses.

Action Potentials↗
PubMed1985

Effects of position on respiratory muscle function during CO2 rebreathing.

The effects of changing from the sitting to supine position on respiratory muscle function was assessed during CO2 rebreathing. Gastric (Pg), pleural (Ppl) and transdiaphragmatic (Pdi) pressures and thoracoabdominal motion were monitored. Diaphragmatic EMG was measured by a bipolar esophageal electrode and quantitated as a moving time average (EMGdi). From sitting to supine, in only 2 of 7 subjects (group A) the diaphragm gained a mechanical advantage as evident by an increased slope of the Pdi versus EMGdi relationship not present in the other 5 subjects (group B). At high levels of ventilation while sitting, only group B increased expiratory abdominal muscle activity leading to a more favorable diaphragm length and a passive descent of the abdomen-diaphragm on inspiration. In the supine position functional residual capacity progressively increased in all subjects and the above abdominal pattern was not seen. We conclude that during upright CO2 rebreathing the recruitment of the expiratory abdominal muscles assists diaphragmatic function by placing the diaphragm in an advantageous pressure generating configuration.

Abdominal Muscles↗
PubMed2004

Cardiopulmonary anatomy and function in long-term survivors of mild to moderate congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: In the last decades, several studies regarding cardiopulmonary sequelae in survivors of congenital diaphragmatic hernia (CDH) have been published, but results often are conflicting, and controversies still exist. The aim of this study was to assess cardiopulmonary anatomic and functional outcome in a group of long-term survivors of CDH of mild to moderate degree. METHODS: Twenty-four children aged 8.15 +/- 2.80 years underwent clinical examination with growth assessment, chest radiographs, echocardiography, pulmonary perfusion scintigraphy, static lung volumes measurement, and spirometry. RESULTS: Mean Z scores of weight for age and height for age were within normal values. Echocardiography showed normal anatomy and function in all but 3 patients with isolated CDH, in whom minor alterations were detected. Mean perfusion to the affected side was significantly lower (45.16 +/- 5.30%; P <.0001) but still within normal range. Four children showed a substantial impairment of perfusion to the hernia side. The mean spirometric values and pulmonary volumes were normal. However, a mild restrictive pattern was evident in 6 children (27.3%), an obstructive pattern in 3 (13.6%), and a mixed obstructive and restrictive impairment in 1. CONCLUSIONS: Hypoplastic lungs of mild to moderate CDH survivors continue to cause pulmonary morbidity in some children many years after the correction of the defect. In particular, lung perfusion appears to be impaired in 20% of the patients and pulmonary function in 45%, without any significant cardiac or developmental sequelae. The negative correlation between FEV1 and duration of ventilation at presentation (r = -0.49; P =.026) may be caused by the consequences of lung hypoplasia, but initial ventilatory management may contribute to increased pulmonary morbidity. Relationship between perfusion and FEF25-75 (r = 0.61; p = 0.004) could reflect an equivalent degree of reduction in the caliber of distal airways and pulmonary vascular tree.

Abnormalities, Multiple↗
PubMed1995

Functional classification of afferent phrenic nerve fibres and diaphragmatic receptors in cats.

1. Single afferent fibres with receptive fields in the diaphragm (272 units) dissected from the right phrenic nerve were classified according to the following properties: reaction to contraction of the diaphragm, resting activity, conduction velocity, location and properties of receptive fields, and reaction to injection of bradykinin and lactic acid into the internal thoracic artery. Nine additional fibres dissected from the phrenic nerve had receptive fields outside the diaphragm. The experiments were performed on chloralose-anaesthetized cats. 2. Ninety-six fibres (36%) had high resting activity when unloaded by contraction of the diaphragm, had low-threshold receptive fields in the muscle and were mostly group II and III fibres. They probably innervated muscle spindles. 3. Eighty-eight fibres (32%) were vigorously activated by contraction of the diaphragm. They had low-threshold receptive fields located in the musculotendinous border and central tendon. Their conduction velocity was in the range for group II and III fibres. We infer that they may innervate tendon organs. 4. Eighty-eight fibres (32%) were slightly affected or not affected by diaphragmatic contraction. They had low- and high-threshold receptive fields located mostly in the muscular part of the diaphragm, and negligible resting activity. Most of them were group III and IV afferent fibres and were activated when bradykinin and lactic acid were applied to their receptive fields. Possibly these low- and high-threshold receptors innervated diaphragmatic ergo- and nociceptors, respectively. 5. Sensory outflow from the diaphragm was found to be somatotopically organized, so that fibres with receptive fields in the sternocostal portion were predominantly located in the upper phrenic nerve root, and those with lumbar receptive fields were in the lower root. 6. It is concluded that the phrenic nerve contains fibres from several distinct classes of sensory receptors: muscle spindles, tendon organs, ergoceptors and nociceptors. The sensory diaphragmatic outflow to the spinal cord is somatotopically organized.

Afferent Pathways↗
PubMed1991

Diaphragmatic electromyogram power-spectral analysis as a function of reduced end-expiratory lung volume.

We examined the centroid frequency (Fc) of the electromyogram power-frequency spectra from the costal (EMGco) and crural (EMGcr) diaphragms at functional residual capacity and at reduced end-expiratory lung volume (EELV) (induced by abdominal banding) in six anesthetized newborn piglets. EMGco and EMGcr were recorded from bipolar electrodes embedded in the costal and crural diaphragms respectively. A fast Fourier transformation of ECG free EMGco and EMGcr was used to compute the power-frequency spectra and calculate the Fc of EMGco and EMGcr. The nitrogen washout technique was used to measure EELV. Abdominal banding induced a reduction in EELV of 30.6% functional residual capacity (range 22-39%). The mean Fc of EMGcr was not significantly altered by the reduction in EELV, whereas the mean Fc of the EMGco fell in every animal at reduced EELV by 13 +/- 8% of baseline Fc (p less than 0.05). We conclude that alterations in lung volume alone can determine changes in the EMGco power spectrum and Fc. Investigators performing EMGco power spectral analysis should consider EELV status when interpreting their findings.

Animals↗
PubMed1995

Monitoring respiratory activity in neonates using diaphragmatic electromyograph.

The monitoring of the development of respiratory function in low-birth-weight or sick neonates is important in its overall treatment. The most direct approach to obtaining information on respiratory function is to monitor the activity of the diaphragmatic muscular system rather than measure the resultant change in lung volume or ventilator output, which cannot be guaranteed to be directly related to the neonate's own respiratory activity. The system was designed to assess the feasibility of monitoring respiratory activity in such neonates by measuring the diaphragmatic electromyograph. It is hoped that this system can be used to monitor the development of lung function and possibly, if reliability proves adequate, the synchronisation and control of ventilator assistance. To monitor the EMG, the dominant effect of the ECG was removed using a digital processor. Initial clinical measurements indicate that neonatal respiratory activity can be monitored by measuring the diaphragmatic EMG. Comparative measurements show the EMG method is faster in detecting the inspiratory phase of a breath. Measurements on ventilated neonates showed the presence of intermittent respiratory activity. It also is proposed that clinically relevant information may be deduced from the analysis of the morphology of the detected EMG waveform.

Diaphragm↗
PubMed1986

Late return of function after intrathoracic torsion of the spleen in congenital diaphragmatic hernia.

A case of late presentation of a left posterolateral diaphragmatic hernia in a four-year-old boy is reported. Shortly after incidental diagnosis of the diaphragmatic hernia, he was admitted with acute abdominal symptoms and laparotomy was performed. The stomach, small intestine, part of the colon, and the spleen were intrathoracic. There was a 720 degree torsion of the splenic pedicle. After reduction, the spleen was placed in the abdomen. At scintiscans 12 days and 14 weeks after operation, no certain splenic function was demonstrated, but at follow-up up 21/2 years later the splenic scan was normal.

Child, Preschool↗
PubMed1994

Diaphragmatic movement in hemiplegic patients measured by ultrasonography.

BACKGROUND: It is known that automatic breathing is controlled by centres in the lower brain stem, whereas volitional breathing is controlled by the cerebral cortical centres. In hemiplegia, lesions above the brain stem result in paralysis of limb muscles. This study was performed to determine whether the diaphragm might also be affected in patients with hemiplegia. METHODS: Studies were performed in six normal control subjects and in eight patients with complete hemiplegia caused by a lesion above the brain stem, all with no known chest disease. Full lung function tests were performed. Diaphragmatic excursion and inspired volume (VT) were measured simultaneously by M mode ultrasonography and respiratory airflow measurements. Recordings of diaphragmatic excursion were performed on each side separately during volitional and automatic breathing at a similar range of VT. RESULTS: Lung function tests lay within the normal range in all the control subjects. In the hemiplegic patients mean (SD) vital capacity was 79 (18)% and residual volume was 123(30)% of predicted. Total lung capacity and functional residual capacity were in the normal range. In the control subjects no significant difference in diaphragmatic excursion was found between volitional and automatic breathing for the same range of inspired volume. By contrast, there was a significant decrease in diaphragmatic excursion during volitional breathing compared with automatic breathing on the affected side in four of the eight hemiplegic patients. CONCLUSIONS: In four of eight hemiplegic patients reduced diaphragmatic movement was present on the paralysed side during volitional inspiration when compared with automatic inspiration. The hemidiaphragm may be involved on the affected side in patients with hemiplegia.

Aged↗
PubMed1996

Congenital diaphragmatic eventration: treatment and postoperative evaluation.

Three patients with congenital diaphragmatic eventration have been reported. The diagnosis was established by chest radiography which showed an abnormally elevated diaphragm. Additionally fluoroscopy, ultrasonography and pulmonary function tests were used. Diaphragmatic plication was performed in order to restore normal pulmonary parenchymal volume and the diaphragm was replaced in its normal localization. All the patients had been discharged in good condition following uneventful postoperative courses. In this study we discussed the etiology, diagnosis, treatment and postoperative courses of diaphragmatic eventration.

Child↗
PubMed1993

The effect of respiratory and lactic acidosis on diaphragm function.

The relative effects of respiratory and metabolic acidosis on diaphragm function are not known. To determine these effects, we compared the effects of respiratory and lactic acidosis on the contractile properties of the diaphragm. We estimated diaphragmatic performance from the change in transdiaphragmatic pressure after supramaximal stimulation of the phrenic nerves in an open-chested, casted-abdomen dog. Similarly, we stimulated the gastrocnemius motor nerve and examined force production and relaxation rate to determine if there was a difference in the response of this skeletal muscle. There was a fall in diaphragm performance with respiratory acidosis (77.1 +/- 16.9 cm H2O versus 93.8 +/- 15.0 cm H2O baseline), but not with lactic acidosis (96.7 +/- 15.7 cm H2O versus 93.8 +/- 15.0 cm H2O baseline); and the gastrocnemius was unaffected by either acidosis. The changes with respiratory acidosis were similar to those seen with diaphragmatic fatigue and had similar relaxation rate changes, suggesting that intracellular pH may play a mechanistic role in respiratory muscle fatigue. In addition, the absence of a respiratory acidosis effect on a non-diaphragmatic skeletal muscle's function represents another physiologic difference between the diaphragm and other skeletal muscles.

Acidosis, Lactic↗
PubMed1992

Sonographic measurement of diaphragmatic motion after coronary artery bypass surgery.

Forty-eight patients were prospectively evaluated following coronary artery bypass grafting (CABG) in order to determine values for diaphragmatic mobility by sonography, to compare diaphragmatic motion to chest x-ray findings, to relate diaphragmatic motion to pulmonary function tests, and to determine whether use of the left internal mammary artery (LIMA), aortic cross-clamp time, or other clinical variables were predictive of diaphragmatic dysfunction. Mean left diaphragmatic motion was 2.8 +/- 1.1 cm (range, 1.0 to 5.7 cm), mean right diaphragmatic motion was 3.9 +/- 1.1 cm (range, 1.8 to 6.4 cm), and ratio of left to right motion was 0.74 +/- 0.27 (range, 0.19 to 1.4). Forty-one patients had normally positioned diaphragms on the chest x-ray film; four of these had poor mobility by ultrasonography (< 1.6 cm). Of the seven elevated left hemidiaphragms on chest x-ray films, three had an excursion of 1.6 cm or more by ultrasonography. The mean FVC for all patients was 59 +/- 13 percent of predicted. There was no relationship between diaphragmatic mobility and FVC or negative inspiratory pressure. The diaphragmatic motion in 36 patients having LIMA grafting was similar to those without (2.7 +/- 1.2 cm [n = 36] vs 2.8 +/- 0.8 cm [n = 12], respectively). Aortic cross-clamp time and respiratory symptoms also did not correlate with diaphragmatic mobility. Sonography can be used in the evaluation of diaphragmatic motion after CABG and may be more accurate in detecting a poorly mobile diaphragm than is the chest x-ray film.

Coronary Artery Bypass↗
PubMed1996

Bilateral lung volume reduction surgery.

A new surgical approach, bilateral lung volume reduction surgery (LVRS), offers hope for select patients with chronic pulmonary emphysema (CPE). Bilateral LVRS procedures involve excision of emphysematous alveoli, which results in a 20% to 30% reduction in the volume of each lung. The goal of LVRS is to improve the respiratory mechanics of patients with CPE by reexpanding functional lung tissue compressed by overdistended emphysematous alveoli, restoring diaphragmatic mobility, and improving the bellows function of the chest wall structures. Patients undergoing bilateral LVRS procedures experience relief from chronic dyspnea and may note improved pulmonary functions and better quality of life.

Humans↗