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Prenatal glucocorticoids and exogenous surfactant therapy improve respiratory function in lambs with severe diaphragmatic hernia following fetal tracheal occlusion.

Fetal tracheal occlusion (TO) accelerates lung growth and can reverse severe lung hypoplasia associated with diaphragmatic hernia (DH), however, lung compliance (Cl) and respiratory gas exchange remain abnormal. We determined the individual and combined effects of prenatal glucocorticoids (GC) and exogenous surfactant therapy (S) on postnatal pulmonary function in lambs with DH that underwent prolonged TO. DH was created in 22 fetal sheep at 65 d of gestation and TO performed at 110 d. Eleven DH/TO animals received prenatal GC (betamethasone, 0.5 mg/kg) 48 h before delivery; six GC-treated and five non-GC lambs were administered surfactant (Infasurf, 3 mg/kg) at birth. Six sham-operated lambs served as controls. Lambs were delivered at 139 d gestation and ventilated for 2 h. GC or surfactant therapy alone significantly improved respiratory gas exchange, Cl, and ventilatory efficiency index. Total lung capacity was normalized only in DH/TO lambs that received both GC and S.

Animals↗

Surgical anatomy of the diaphragm and the phrenic nerve.

In this article, the anatomy of the diaphragm and phrenic nerves is discussed, together with related surgical implications. Since the major cause of phrenic nerve injury is surgery, usually for congenital or acquired heart disease, incisions in the diaphragm that do not injure major branches of the phrenic nerve are also discussed. Diaphragmatic plication is usually required in infants less than 3 months of age, and older children may be managed by ventilatory support if electrophysiologic studies document the possibility of return of nerve function. In adults with normal pulmonary function, unilateral diaphragmatic paralysis is usually asymptomatic.

Adult↗

[Functional state of the diaphragm during several non-drug methods of the treatment of chronic pulmonary insufficiency].

The study compared the effect of conventional therapy of aggravated chronic obstructive bronchitis (COB), inpatient oxygen treatment of large duration (OT), normobaric hypoxic stimulation (NBHS), inspiratory resistance on the diaphragmatic muscle function in COB patients with chronic pulmonary insufficiency. The function was assessed at stimulation electromyography of the diaphragm. The latter reflected enhanced bioelectric activity of the diaphragm in response to OT and inspiratory resistive training as shown by increased time parameters. Conventional COB treatment induced no changes in the myographic picture. Long-term response to NBHS needs further investigations.

Bronchitis↗

Lung function after repair of congenital diaphragmatic hernia.

To study lung development after repair of congenital diaphragmatic hernia 20 patients operated on between 1960 and 1976 were followed-up at 6-22 years of age. All had had an uneventful postoperative course, had no concomitant disease and were subjectively well with an ordinary physiological performance. The investigation showed a mean increase of residual volume by one third of predicted normal values. Fractional perfusion and ventilation were reduced by 20% on the hernia side compared with the contralateral side. Functional impairment owing to pulmonary hypoplasia was ruled out by the existence of a normal working capacity and maintenance of a normal alveolar gas exchange during exercise on a high work load.

Child, Preschool↗

Resting and exercise cardiorespiratory function in survivors of congenital diaphragmatic hernia.

Our objective was to study exercise capacity and cardiorespiratory response to exertion in survivors of congenital diaphragmatic hernia (CDH). This was a cross-sectional cohort study of 23 CDH survivors, aged 10-16 years, and 23 gender- and age-matched controls. Exercise testing was performed on a cycle ergometer, with cardiac output measurements made using exponential CO2 rebreathing. Pretest cardiorespiratory assessment was done by echocardiography and pulmonary function testing. Statistical analysis was performed using Student's t-test, regression analysis, and longitudinal model computing with spatial covariance structure. No echocardiographic evidence for pulmonary hypertension was found at rest (right ventricular systolic pressures, 27 +/- 6 mmHg). Mean pulmonary artery diameter on the side of the CDH was significantly smaller than contralaterally, but was within normal range (z-score, 0 +/- 1.1 vs. 1.2 +/- 1.6, P < 0.01). Exercise capacity was mildly reduced in CDH compared to controls and predictive data (maximum workload, 77% +/- 12% vs. 91% +/- 16% of predicted, P < 0.01). Cardiorespiratory response to exertion was not significantly different between groups. In conclusion, most adolescent CDH survivors have nearly normal exercise capacity and cardiorespiratory response to exertion. This study may prove useful in comparisons with future cohorts comprising more severely affected individuals now surviving due to improved neonatal care.

Adolescent↗

[Severity and prognosis of congenital diaphragmatic hernia from the viewpoint of perioperative respiratory function].

We studied severity and prognosis of congenital diaphragmatic hernia (CDH) by using preductal arterial blood gas analysis (BGA) and pulmonary function tests (PFTs) in 29 newborn infants. CDH was diagnosed within 24 hours of life, and surgical repair was performed through an abdominal approach after a period of stabilization. The infants were classified into the following three groups based on the highest preoperative alveolar-arterial oxygen tension difference (A - aDO2) and the lowest arterial carbon dioxide pressure (PaCO2) values; Group A (n = 15) : A - aDO2 < 500 mmHg, PaCO2 < 40 mmHg, Group B (n = 7) : A - aDO2 > or = 500 mmHg, PaCO2 < 40 mmHg, Group C (n = 7) : A - aDO2 > or = 500 mmHg, PaCO2 > or = 40 mmHg. Furthermore, the patients were classified into the following three groups based on the preoperative respiratory system compliance (Crs) and forced vital capacity (FVC) values; Group D (n = 8) : Crs < 0.5 ml.cmH2O-1.kg-1, FVC < 10 ml.kg-1, Group E (n = 4) : Crs < 0.5 ml.cmH2O-1.kg-1, FVC > or = 10 ml.kg-1, Group F (n = 17) : Crs > or = 0.5 ml.cmH2O-1.kg-1, FVC > or = 10 ml.kg-1. The mortality in the Group C was significantly higher than in the Group A and B, and the preoperative Crs and FVC values in the Group C were significantly lower than the other groups. The mortality in the Group D and E were significantly higher than the Group F. In conclusion, it is suggested that the preoperative Crs value less than 0.5 ml.cmH2O-1.kg-1 indicates severe pulmonary hypoplasia and is critical for survival.

Blood Gas Analysis↗

Respiratory muscle function in myasthenia gravis.

Global respiratory muscle function and diaphragmatic strength were assessed and compared with quadriceps femoris muscle strength in 17 patients with generalized mild-to-moderate myasthenia gravis and breathlessness. Initial measurements, made 10 h after the last dose of oral anticholinesterase therapy, demonstrated reduced maximal static expiratory (52.4 +/- 26.8% predicted) and inspiratory (54.0 +/- 23.5% predicted) mouth pressures in 16 patients, and reduced quadriceps femoris muscle strength in all cases. Vital capacity (VC) (70.9 +/- 19.0% predicted) was abnormal in 12 patients. Transdiaphragmatic pressure recorded during maximal sniffs (sniff Pdl) was reduced in eight patients, whereas pressure recorded during bilateral phrenic nerve stimulation at 1 Hz (twitch Pdi) was reduced in only three. There was no relationship between the grade of myasthenia or the severity of dyspnea and any of the measurements of respiratory muscle strength. After the administration of edrophonium hydrochloride (Tensilon), there was a significant increase in maximal static expiratory and inspiratory mouth pressures in quadriceps muscle strength and in sniff Pdi. The small increase in VC was not significant, and twitch Pdi increased in only one patient. Phrenic nerve conduction time was normal before and after Tensilon. Two patients with severe long-standing myasthenia showed no improvement in any measurement after Tensilon. We conclude that expiratory and inspiratory muscle weakness was not uncommon in patients with myasthenia gravis. Respiratory muscle strength improved after Tensilon. Vital capacity was a less sensitive measure of respiratory muscle strength than were respiratory mouth pressures and sniff Pdi. Diaphragmatic involvement was not detected by twitch Pdi unless the weakness was severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fibrillins 1 and 2 perform partially overlapping functions during aortic development.

Fibrillin-rich microfibrils are extracellular assemblies that impart structural properties to the connective tissue. To elucidate the contribution of fibrillin-rich microfibrils to organogenesis, we have examined the vascular phenotype of a newly created strain of mice that completely lacks fibrillin-1 and the consequences of combined deficiency of fibrillins 1 and 2 on tissue formation. The results demonstrated that fibrillins 1 and 2 perform partially overlapping functions during aortic development. Fbn1-/- mice died soon after birth from ruptured aortic aneurysm, impaired pulmonary function, and/or diaphragmatic collapse. Analysis of the neonatal Fbn1-/- aorta documented a disorganized and poorly developed medial layer but normal levels of elastin cross-links. Transcriptional profiling revealed that aneurysm progression in Fbn1 null mice is accompanied by unproductive up-regulation of gene products normally involved in tissue repair and vascular integrity, such as plasminogen activator inhibitor-1, activin A, and cysteine-rich angiogenic protein 61. In contrast to Fbn1-/- mice, Fbn2 null mice had a well developed and morphologically normal aortic wall. However, virtually all Fbn1-/-;Fbn2-/- embryos and about half of the Fbn1+/-;Fbn2-/- embryos died in utero and displayed a significantly more severe vascular phenotype than Fbn1-/- mice. Consistent with a specialized function of fibrillin-2, electron microscopy visualized ultrastructurally different microfibrils in Fbn1 null compared with control cell cultures. Collectively, these data demonstrate that involvement of fibrillin-2 in the initial assembly of the aortic matrix overlaps in part with fibrillin-1 and that continued fibrillin-1 deposition is absolutely required for the maturation and function of the vessel during neonatal life.

Activins↗

Pleural bupivacaine placement for optimal postthoracotomy pulmonary function: a prospective, randomized study.

OBJECTIVE: To determine dependent chest tube losses of bupivacaine with paravertebral versus interpleural administration, thereby helping to explain the significant differences in pulmonary function that exist between these two techniques. DESIGN: A prospective, randomized study. SETTING: A single hospital. PARTICIPANTS: Twelve adult patients undergoing posterolateral thoracotomies. INTERVENTIONS: Paravertebral or interpleural administration of bupivacaine. MEASUREMENTS AND MAIN RESULTS: Analgesia, as assessed by visual analog pain scores and patient-controlled morphine requirements, was similar in both groups. Postoperative spirometric values were significantly better at most times with the paravertebral route of administration. Dependent chest tube bupivacaine losses were approximately four times higher in the interpleural group. CONCLUSION: Local anesthetic on the diaphragm might actively impair respiratory function through diaphragmatic and abdominal muscle weakness, while failing to contribute to pain relief.

Aged↗

Asynchronous respiratory activity of the diaphragm during spontaneous breathing in the lamb.

1. Direct simultaneous recordings from chronically implanted electrodes in different parts of the diaphragm were made in young lambs in which laryngeal adductor (thyroarytenoideus) and intercostal electromyograms, airflow, tracheal pressure and electrocorticogram and electro-oculograms for behavioural state were also recorded.2. An asynchrony of diaphragmatic contraction occurred which was dependent on sleep state. The vertebral portion showed maximal post-inspiratory activity while the lateral paratendinous portion usually terminated abruptly with end-inspiration, reciprocating closely with the onset of expiratory laryngeal adductor activity during quiet sleep. The contraction of the sternal portion was similar to the vertebral portion. In active (rapid eye movement) sleep there was no expiratory laryngeal constriction and post-inspiratory activity occurred in all portions of the diaphragm. During the characteristic bursts of rapid breathing in active sleep all post-inspiratory activity disappeared and the diaphragm contracted synchronously.3. General anaesthesia (Halothane/N(2)O or Nembutal) abolished expiratory laryngeal adductor activity and the discharge pattern became similar in all parts of the diaphragm.4. Intrathoracic vagotomy of Xylocaine blockade below the recurrent laryngeal nerves abolished post-inspiratory activity in all parts of the diaphragm, in contrast to the effect on expiratory laryngeal adductor activity which increased.5. Sustained ;tonic' electromyographic activity was often recorded from the costal and to a lesser extent the paratendinous portion of the diaphragm. This activity related to adjacent intercostal activity:ipsilateral intercostal blockade with local anaesthetic (Xylocaine 1%) abolished both the intercostal and the ;tonic' activity of the costal margins of the diaphragm. Conversely ipsilateral phrenic nerve blockade abolished all but the ;tonic' activity which related to intercostal activity.6. Interpretation of the respiratory activity of the diaphragm could not be made adequately from conventionally placed electrodes (i.e. costal, sternal slip or surface) during spontaneous breathing in unanaesthetized lambs. Simultaneous recordings showed that while expiratory flow and duration were actively controlled by expiratory laryngeal adductor activity and the diaphragm, the latter performed asynchronously. While both laryngeal and diaphragmatic expiratory functions were substantially under vagal control, the former increased and the latter decreased with reduced vagal input.

Anesthesia, General↗

Management of fetal urinary tract anomalies detected by prenatal ultrasonography.

Over a three and a half year period 32 babies were referred with a urinary tract anomaly diagnosed by prenatal ultrasound. This diagnosis was subsequently confirmed in 19 infants by postnatal assessment. Three of 13 infants in whom the original diagnosis was incorrect were subsequently found to have intra-abdominal pathology but no urological anomaly, while the other 10 had lesions in the urinary tract but not those suggested prenatally. Nineteen of the 29 babies with urological abnormalities were clinically normal at birth; 20 underwent surgery. There were three deaths; two from a combination of renal and pulmonary failure secondary to posterior urethral valves, and a third (in an infant who had normal renal function) from diaphragmatic hernia and cardiac anomalies. Prenatal diagnosis was thought to have been of benefit in six patients, of probable benefit in 16, and of no benefit in seven.

Humans↗

Phrenic neuropathy in chronic renal failure.

BACKGROUND: Peripheral neuropathy and alterations in diaphragmatic muscle function are frequently caused by uraemia. Phrenic nerve function in patients with end stage renal failure, however, has not been examined to date. METHODS: An electrophysiological study of the phrenic nerve was performed to determine its possible involvement in 32 nondiabetic patients with end stage renal disease undergoing chronic haemodialysis. RESULTS: Seventeen patients had electrophysiological signs of peripheral neuropathy in at least one of the investigated nerves and 14 of the 17 showed pathological phrenic nerve latencies. Delayed phrenic nerve latencies correlated clearly with pathological peroneal nerve conduction velocities. CONCLUSIONS: Phrenic neuropathy is a frequent complication of uraemia.

Adolescent↗

Elevated diaphragm electromyogram during neonatal hypoxic ventilatory depression.

Diaphragmatic electromyogram (EMG) was obtained in eight 48-h-old unanesthetized monkeys while breathing air and then either of two different hypoxic gas mixtures (12 or 8% O2 in N2) for 5 min. Minute ventilation (VI) rose significantly above control levels by 1 min of hypoxemia while animals were breathing either of the hypoxic gas mixtures as tidal volume (VT) and slope and rate moving average EMG increased. The relative gains in VI were associated with comparable increases in diaphragmatic neural activity per minute (EMG/min = peak EMG X frequency) during this early phase of hypoxemia. VI subsequently fell to control levels (inspired O2 fraction = 12%, arterial PO2 = 23 +/- 3 Torr) or significantly below (inspired O2 fraction = 8%, arterial PO2 = 18 +/- 0.4 Torr) by 5 min of hypoxemia, secondary to changes in VT. Despite the decline in VI, slope and rate moving average EMG, and EMG/min remained statistically above control values by 5 min of hypoxemia, although there was a trend for EMG/min to decrease slightly from the 1-min peak response. These findings demonstrate that hypoxic-induced depression of neural input to the diaphragm is not independently responsible for the biphasic nature of the newborn ventilatory response, although it cannot be ruled out as a contributor. The fall in inspiratory volumes despite constant elevated EMG activity suggests the presence of a change in respiratory mechanics and/or an impairment in diaphragmatic contractile function without offsetting neural compensatory activity.

Animals↗

Relationship between axial motion and volume displacement of the diaphragm during VC maneuvers.

During semistatic inspiratory and expiratory vital capacity (VC) maneuvers, axial motion of the diaphragm was measured by lateral fluoroscopy and was compared with diaphragmatic volume displacement. Axial motion was measured at the anterior, middle, and posterior parts of the diaphragm, and the mean of these measurements was used. The volume displacement was calculated in two ways: first, from respiratory inductive plethysmograph-(Respitrace) derived cross-sectional area changes of rib cage and abdomen (Vdi,RIP) by means of a theoretical analysis described by Mead and Loring (J. Appl. Physiol. 53: 750-755, 1982) and, second, from fluoroscopically measured changes in position and anteroposterior surface of the diaphragm (Vdi,F). A very good linear relationship was found between Vdi,RIP and Vdi,F during inspiration as well as expiration (r greater than 0.95), indicating that the analysis of Mead and Loring was valid in the conditions of the present study. The diaphragmatic volume displacement (active or passive) accounted for 50-60% of VC. A very good linear relationship was also found between mean axial motion and volume displacement of the diaphragm measured with both methods during inspiration and expiration (r greater than 0.98). Our data suggest that, over the VC range, diaphragmatic displacement functionally can be represented by a pistonlike model, although topographically and anatomically it does not behave as a piston.

Adult↗

Mechanical ventilation results in progressive contractile dysfunction in the diaphragm.

These experiments tested the hypothesis that a relatively short duration of controlled mechanical ventilation (MV) will impair diaphragmatic maximal specific force generation (specific P(o)) and that this force deficit will be exacerbated with increased time on the ventilator. To test this postulate, adult Sprague-Dawley rats were randomly divided into one of six experimental groups: 1) control (n = 12); 2) 12 h of MV (n = 4); 3) 18 h of MV (n = 4); 4) 18 h of anesthesia and spontaneous breathing (n = 4); 5) 24 h of MV (n = 7); and 6) 24 h of anesthesia and spontaneous breathing (n = 4). MV animals were anesthetized, tracheostomized, and ventilated with room air. Animals in the control group were acutely anesthetized but were not exposed to MV. Animals in two spontaneous breathing groups were anesthetized and breathed spontaneously for either 18 or 24 h. No differences (P > 0.05) existed in diaphragmatic specific P(o) between control and the two spontaneous breathing groups. In contrast, compared with control, all durations of MV resulted in a reduction (P < 0.05) in diaphragmatic specific tension at stimulation frequencies ranging from 15 to 160 Hz. Furthermore, the MV-induced decrease in diaphragmatic specific P(o) was time dependent, with specific P(o) being approximately 18 and approximately 46% lower (P < 0.05) in animals mechanically ventilated for 12 and 24 h, respectively. These data support the hypothesis that relatively short-term MV impairs diaphragmatic contractile function and that the magnitude of MV-induced force deficit increases with time on the ventilator.

Animals↗

Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin.

Although it is known that endotoxin can induce diaphragmatic dysfunction, the mechanism of this effect is not fully understood. However, because the effects of endotoxin on other tissues appear to be mediated in part by free radicals, the present study sought to determine if free radicals may also contribute to the diaphragmatic dysfunction induced by endotoxin administration. Studies were performed on four groups of hamsters. One group of animals received intraperitoneal injections of endotoxin on the first and second days of study (i.e., 10 and 20 mg/kg, respectively). The second group received saline rather than endotoxin, the third group received both endotoxin and a free radical scavenger, PEG-SOD (2,000 U/kg given intraperitoneally every 12 h on Days 1 and 2), and the fourth group received PEG-SOD alone. All groups were killed on the third study day (i.e., 48 h after the initial injections). Diaphragmatic contractile function was assessed in vitro using muscle strips excised from the costal diaphragms of freshly killed animals; diaphragm samples were also assayed for malondialdehyde (MDA), a commonly used index of free-radical-mediated lipid peroxidation. MDA levels were higher in diaphragms from endotoxin-treated animals than from saline-treated control animals, and the contractility of diaphragm strips from endotoxin-treated animals was reduced when compared with strips from saline-treated control animals. Administration of PEG-SOD prevented MDA formation and contractile dysfunction in endotoxin-treated animals. Diaphragm contractility and MDA levels for animals given PEG-SOD alone were similar to those for saline-treated control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗