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Congenital diaphragmatic hernia prevents absorption of distal air space fluid in late-gestation rat fetuses.

We hypothesized that congenital diaphragmatic hernia (CDH) may decrease distal air space fluid absorption due to immaturity of alveolar epithelial cells from a loss of the normal epithelial Na+ transport, as assessed by amiloride and epithelial Na+ channel (ENaC) and Na-K-ATPase expression, as well as failure to respond to endogenous epinephrine as assessed by propranolol. Timed-pregnant dams were gavage fed 100 mg of nitrofen at 9.5-day gestation to induce CDH in the fetuses, and distal air space fluid absorption experiments were carried out on 22-day gestation (term) fetuses. Controls were nitrofen-exposed fetuses without CDH. Absorption of distal air space fluid was measured from the increase in 131I-albumin concentration in an isosmolar, physiological solution instilled into the developing lungs. In controls, distal air space fluid absorption was rapid and mediated by beta-adrenoceptors as demonstrated by reversal to fluid secretion after propranolol. Normal lung fluid absorption was also partially inhibited by amiloride. In contrast, CDH fetuses continued to show lung fluid secretion, and this secretion was not affected by either propranolol or amiloride. CDH lungs showed a 67% reduction in alpha-ENaC and beta-ENaC expression, but no change in alpha1-Na-K-ATPase expression. These studies demonstrate: 1) CDH delays lung maturation with impaired distal air space fluid absorption secondary to inadequate Na+ uptake by the distal lung epithelium that results in fluid-filled lungs at birth with reduced capacity to establish postnatal breathing, and 2) the main stimulus to lung fluid absorption in near-term control fetuses, elevated endogenous epinephrine levels, is not functional in CDH fetuses.

Absorption↗

Estrogen treatment and gonadal function in the regulation of lipoprotein lipase.

Lipoprotein lipase (LPL) activity was measured in adipose tissue, heart and diaphragm in Sprague--Dawley rats after estrogen therapy or orchiectomy. Enzyme activity was measured by incubation of tissue fragments with a triolein emulsion in the presence of serum and heparin. In confirmation of other work, depression of adipose tissue LPL followed estradiol treatment in pharmacologic or near-physiologic doses. Cardiac and diaphragmatic muscle LPL were increased. Estrogen-treated male animals showed growth retardation. However, they gained weight steadily and did not show significant differences in serum insulin, glucose of D-beta-hydroxybutyrate. The effects of estradiol in male animals were reversed by sequential fasting and re-feeding. At times during growth and aging in normal female rats, adipose tissue activity was decreased while cardiac and skeletal muscle activities were increased relative to males of the same age or body weight. Castration of male rats failed to reproduce the effect of estrogens on tissue lipoprotein lipase. These in vitro data suggest that exogenous estrogens may shift the flux of triglyceride fatty acids from storage in the adipose organ toward incorporation by muscle. These, and other data, raise the possibility that physiological estrogen secretion exerts a tonic influence over the synthesis and ultimate destination of triglyceride fatty acids.

Adipose Tissue↗

Right hemi-diaphragm paralysis following cardiac radiofrequency ablation.

Diaphragm paralysis may occur after traumatic phrenic nerve injury. Here we report three patients in whom right hemi-diaphragmatic paralysis developed after cardiac radiofrequency ablation. We hypothesise that local focused thermal energy at the time of the ablation may have caused direct neuronal damage by axonal coagulation necrosis. The prognosis for this type of injury may be reasonably good; two of the three patients fully recovered diaphragm function by 1 year.

Adult↗

Pulmonary arterial Doppler velocimetry in fetuses with lung hypoplasia.

OBJECTIVE: The aim of the study was to examine Doppler flow velocity waveforms in the main stems of the pulmonary arteries in fetuses with autopsy-proven lung hypoplasia and to find out whether in these conditions typical patterns can be found. STUDY DESIGN: Doppler spectra were derived from the main stem of the right or left pulmonary artery in fetuses at high-risk for lung-hypoplasia. The following Doppler parameters were analyzed and compared to reference ranges: peak systolic velocity, acceleration time, time velocity integral, end-systolic reverse flow, pulsatility index (PI). Pulmonary hypoplasia was found in nine cases at autopsy after termination of pregnancy (19-23 weeks). According to etiology, three groups were considered: (A) bilateral renal malformations (n=4), (B) congenital diaphragmatic hernia (n=2), and (C) miscellaneous malformations including heart defects (n=3). RESULTS: The following Doppler parameters were found: normal values in end-systolic reversal flow in all cases, decreased peak systolic velocity and acceleration time in 3/9, decreased time velocity integral in 4/9 and increased pulsatility index in 6/9. Considering the etiology of pulmonary hypoplasia the pulsatility index was found to be the most sensitive, since all fetuses in groups A and B had an abnormal PI. CONCLUSIONS: Human fetuses with renal malformations and diaphragmatic hernia associated with lung hypoplasia show as early as 19-23 weeks of gestation an abnormal Doppler spectrum in the main stems of the pulmonary arteries. Increased PI is the best parameter to detect flow abnormality in this condition. Since the Doppler spectrum depends on cardiac anatomy and function, PI in lung hypoplasia seems to be reliable only when cardiac defects are absent.

Blood Flow Velocity↗

Optimal arrangement of magnetic coils for functional magnetic stimulation of the inspiratory muscles in dogs.

In an attempt to maximize inspiratory pressure and volume, the optimal position of a single or of dual magnetic coils during functional magnetic stimulation (FMS) of the inspiratory muscles was evaluated in twenty-three dogs. Unilateral phrenic magnetic stimulation (UPMS) or bilateral phrenic magnetic stimulation (BPMS), posterior cervical magnetic stimulation (PCMS), anterior cervical magnetic stimulation (ACMS) as well as a combination of PCMS and ACMS were performed. Trans-diaphragmatic pressure (Pdi), flow, and lung volume changes with an open airway were measured. Transdiaphragmatic pressure was also measured with an occluded airway. Changes in inspiratory parameters during FMS were compared with 1) electrical stimulation of surgically exposed bilateral phrenic nerves (BPES) and 2) ventral root electrical stimulation at C5-C7 (VRES C5-C7). Relative to the Pdi generated by BPES of 36.3 +/- 4.5 cm H2O (Mean +/- SEM), occluded Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and a combined PCMS + ACMS were 51.7%, 61.5%, 22.4%, 100.3%, and 104.5% of the maximal Pdi, respectively. Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and combined ACMS + PCMS were 38.0%, 45.2%, 16.5%, 73.8%, and 76.8%, respectively, of the Pdi induced by VRES (C5-C7) (48.0 +/- 3.9 cm H2O). The maximal Pdi(s) generated during ACMS and combined PCMS + ACMS were higher than the maximal Pdi(s) generated during UPMS, BPMS, or PCMS (p < 0.05). ACMS alone induced 129.8% of the inspiratory flow (73.0 +/- 9.4 L/ min) and 77.5% of the volume (626 +/- 556 ml) induced by BPES. ACMS and combined PCMS + ACMS produce a greater inspiratory pressure than UPMS, BPMS or PCMS. ACMS can be used to generate sufficient inspiratory pressure, flow, and volume for activation of the inspiratory muscles.

Animals↗

Muscular, bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract.

1. The effects of mechanical stimulation in the nose, epipharynx, laryngopharynx and tracheobronchial tree, and of chemical irritation of the nasal mucosa, were studied on various somatic and autonomic functions in cats.2. Action potentials were recorded from the diaphragm and rectus abdominis muscles of spontaneously breathing cats, and from the phrenic and lumbar nerves of paralysed, artificially ventilated cats. Expulsive processes such as sneezing and coughing evoked from the nasal, laryngopharyngeal and tracheobronchial mucosae were characterized by strong diaphragmatic and abdominal expiratory discharges; synchronous discharges in these antagonistic respiratory muscles and their motoneurones often occurred especially during laryngopharyngeal stimulation of coughing.3. The ;aspiration reflex' elicited from the epipharynx was characterized by brief bursts of high-frequency activity in the phrenic nerve and diaphragm, and was usually not followed by any expiratory activity in the rectus abdominis or its motoneurones.4. In paralysed, artificially ventilated cats stimulation of the laryngeal and tracheobronchial regions caused large increases both in total lung resistance and in tracheal constrictor nerve fibre activity, indicating reflex tracheo-bronchoconstriction; similar stimulation of the epipharyngeal and nasal mucosae decreased both total lung resistance and tracheal constrictor nerve fibre activity, indicating reflex bronchodilation.5. In paralysed cats, stimulation of each of the four sites in the respiratory tract caused a reflex increase in systemic blood pressure, the largest hypertensive response coming from the epipharynx. Nervous activity in cervical sympathetic efferent fibres was increased by the stimulations, especially those of the epipharyngeal and laryngopharyngeal regions.6. There was good correlation in time and magnitude between the changes in total lung resistance and in bronchoconstrictor fibre activity, and also between the changes in blood pressure and in efferent sympathetic discharge, although the mechanical changes lagged behind the nervous ones.7. In anaesthetized, spontaneously breathing cats stimulation of the respiratory tract evoked large variations in blood pressure accompanying the spasmodic respiratory efforts, probably by mechanical effects.

Action Potentials↗

Factors influencing ventilatory muscle recruitment in patients with chronic airflow obstruction.

Patients with chronic airflow obstruction (CAO) frequently develop abnormal thoraco-abdominal excursion, but the patterns described are inconsistent and the factors that relate to their development remain unknown. We studied 45 stable patients with FEV1 ranging from 0.36 to 2.1 L. A pattern of ventilatory muscle recruitment (VMR) was established by simultaneously measuring gastric (Pg) and pleural (Ppl) pressures and rib cage (Vrc) and abdominal (Vab) volume displacement with inductance plethysmography. From these tracings, Pg-Ppl plots were constructed and the delta Pg/delta Ppl values were calculated. The delta Pg/delta Ppl was validated in 15 patients with simultaneous analysis of Vab-Pg plots. Pearson's test and multiple regression analyses were used to correlate delta Pg/delta Ppl to factors thought to influence respiratory muscle function such as age, sex, nutritional status (weight/height, albumin), hyperinflation, airflow obstruction, and arterial blood gases. We found a direct correlation between a more positive delta Pg/delta Ppl value and increasing hyperinflation (r = 0.69, p less than 0.0001), increasing airflow obstruction (r = -0.55, p less than 0.001), and decreasing diaphragmatic strength (r2 = 0.32, p less than 0.001). We also found that expiratory Ppl became more positive with decreasing FEV1 (r2 = 0.33, p less than 0.001). This change in VMR was independent of age, sex, nutritional status, and arterial blood gas determinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Five years' experience of combination therapy: peritoneal dialysis with hemodialysis.

The fundamental objective of dialysis is to maintain the dose of solute clearance and ultrafiltration (UF). When peritoneal dialysis (PD) patients cannot maintain the target dose of clearance [weekly Kt/V > 2.0, weekly creatinine clearance (CCr) > 60 L/1.73 m2], the dialysis dose needs to be increased. But the means of increasing the dose only by PD are limited, especially for patients with UF failure (UFF). Combination therapy--PD with hemodialysis (PD + HD)--is the simplest way to solve the problem. The purpose of PD + HD therapy is to support solute clearance and UF when PD alone cannot meet the necessary targets. Acute and transient dialysis cases should be excluded. The general prescription for PD + HD should be 5-6 days of PD weekly and 1 session of HD weekly. For determine the adequacy of PD + HD, we adopted the equivalent renal clearance (EKR), transforming the PD weekly Kt/V and then evaluating total clearance from both modalities. Of our 238 dialysis patients, 31 (13%) use combined therapy. Except for 1 patient that transferred from long-term HD, all of patients had been on PD for more than 60 months, and were experiencing uremic symptoms after decline of residual renal function. In 12 cases, the problem was lack of solute clearance; in 5 cases, it was UFF. High permeability was involved in 5 cases: 4 after long-term PD and 1 from the start of PD. Poor self-management occurred in 9 cases. Contributing factors included hernia, diaphragmatic intercourse, and severe heart failure with strict fluid control. Among the 31 patients, 8 used HD twice weekly. After combination therapy was started, the dialysis dose increased and body fluids became controllable. As a result, uremic symptoms improved and the patients' quality of life increased.

Humans↗

Influence of endurance exercise on respiratory muscle performance.

PURPOSE: During high-intensity, exhaustive, constant-load exercise above 85% of maximal oxygen consumption, the diaphragm of healthy subjects can fatigue. Although a decrease in trans-diaphragmatic pressure is the most objective measure of diaphragmatic fatigue, possible extra-diaphragmatic muscle fatigue would not be detected by this method. The aim of the present study was to investigate the impact of exhaustive, constant-load cycling exercise at different intensities on global respiratory performance determined by the time to exhaustion while breathing against a constant resistance. METHODS: Ten healthy, male subjects performed an exhaustive cycling endurance test at 65, 75, 85, and 95% of peak oxygen consumption (VO2peak). Before cycling (to) as well as at 10 min (t10) and 45 min (t45) after cycling, respiratory performance was determined. RESULTS: Breathing endurance was equivalently reduced after exhaustive cycling at either 65% (8.4 +/- 4.1 min [t0] vs 3.9 +/- 2.8 min [t10]), 75% (9.9 +/- 6.1 vs 4.4 +/- 2.8 min), 85% (9.3 +/- 6.0 vs 3.8 +/- 2.9 min), or 95% VO2peak (8.5 +/- 5.1 vs 4.0 +/- 2.5 min) and, therefore, was independent of exercise intensity. CONCLUSION: This result contradicts previous findings, possibly due to the fact that extra-diaphragmatic muscles are tested in addition to the diaphragm during resistive breathing.

Adult↗

Physiological basis of improvement after lung volume reduction surgery for severe emphysema: where are we?

Lung volume reduction surgery has become an accepted therapeutic option to relieve the symptoms of selected patients with severe emphysema. In a majority of these patients, it causes objective as well as subjective functional improvement. A proper understanding of the physiological determinants underlying these beneficial effects appears very important in order to better select patients for the procedure that is currently largely carried out on an empirical basis. Lung volume reduction surgery has two distinct effects. Firstly, it causes an increased elastic recoil, which at least partially explains the enhanced maximal expiratory flow. Secondly, it is associated with a reduction of hyperinflation which allows for an increase in global inspiratory muscle strength and in diaphragmatic contribution to tidal volume as well as a decrease in the inspiratory elastic load imposed by the chest wall. Taken together, these effects result in a reduced work of breathing and in an enhanced maximal ventilation which both contribute to the increased exercise capacity and reduced dyspnoea after surgery. The improved lung recoil and the reduced hyperinflation after volume reduction surgery were the primary postulates upon which the usual selection criteria for the procedure were based. It is now likely that these are correct. Nevertheless, some patients do not benefit from lung volume reduction surgery and the current literature does not allow for a refinement of the selection process from a physiological point of view. The exact mechanisms underlying the improvement in lung recoil, lung mechanics, and respiratory muscle function remain incompletely understood. Moreover, the effects of lung volume reduction surgery on gas exchange and pulmonary haemodynamics still need to be more fully investigated. An analysis of the characteristics of patients who do not benefit from the procedure and the development of an animal model for lung volume reduction surgery would probably help address these important issues.

Exercise Tolerance↗

Long-term developmental outcome of children with complex congenital heart disease.

As the mortality of neonatal and infant surgery for CHD continues to decrease, attention is now focused on long-term sequelae, especially later cognitive and neurologic function, in survivors. Although children with repaired or palliated CHD have an increased risk for neurocognitive deficits, most survivors are performing within the normal range for most standardized measures. Even those children at highest risk, such as patients with HLHS, are comparable with survivors of other congenital lesions, such as diaphragmatic hernia, or low-birth weight children. Continued efforts are underway to reduce cerebral injury before, during, and after congenital heart surgery.

Developmental Disabilities↗

Gas exchange and exercise tolerance following bullectomy.

This study evaluates the physiological responses to giant bullectomy. A 42-year-old female with bilateral giant bullae presented with dyspnoea and exercise limitation. At baseline and 3 months after bullectomy she had tests of lung function; exercise capacity via a symptom-limited cycle test and a 6-min walk test (6MWT). Quality of life (QoL) and gas exchange using the multiple inert gas elimination technique (MIGET) were also assessed. There were significant improvements in pulmonary function following surgery with the FEF(25-75%) predicted increasing from 16 to 96. The 6MWT increased by 10% and the peak leg work capacity by 48%. A MIGET measure of the distribution of perfusion (Log SDQ) fell from 0.52 to 0.36. There was also radiological improvement in hyperinflation and diaphragmatic configuration. The QoL total score decreased from 56 to 25. This patient demonstrated significant improvements in exercise tolerance, gas exchange and QoL following bullectomy.

Adult↗

Effects of aging on ventilatory and occlusion pressure responses to hypoxia and hypercapnia.

Studies were performed to examine the decrease in ventilatory response to hypoxia and hypercapnia in the elderly and to explore its etiology. For this purpose, matched groups of normal elderly (65 to 79 yr of age) and young subjects were used. Standard pulmonary function tests were supplemented in both groups by determination of total respiratory compliance and the ventilatory responses to hyperoxic hypercapnia and isocapnic hypoxia using rebreathing methods. While testing the ventilatory responses, we recorded minute ventilation and its components, as well as mouth occlusion pressures, and rib cage and abdominal-diaphragmatic compartmental ventilation (magnetometry). We found that ventilatory responses to both hypercapnia and hypoxia were reduced in the elderly by approximately 50%. These reductions were not related to any change in control of respiratory timing, but to a large reduction in mean inspiratory airflow. The reduced airflow could not be attributed to alterations in pulmonary mechanics since the differences in mechanics between the groups were small. Instead, since the occlusion pressure responses to hypercapnia and hypoxia were reduced in the elderly proportionately to the ventilatory responses, reduction in neuromuscular inspiratory output was likely to be the major factor.

Adult↗

Pulmonary edema in a woman following fetal surgery.

Most cases of acute lung injury in pregnancy are attributed to hydrostatic pulmonary edema. In this report, however, we describe a 20-year-old pregnant woman who developed a unique case of increased permeability pulmonary edema following surgery for the repair of a fetal congenital diaphragmatic hernia. Two days after surgery, the patient developed acute respiratory failure and diffuse alveolar edema, requiring intubation and positive pressure ventilation for 5 days. The diagnosis of increased permeability pulmonary edema was confirmed by the ratio of pulmonary edema fluid to plasma protein (ratio=0.99). The patient received IV nitroglycerine for tocolysis. As a nitric oxide donor, the nitroglycerine may have combined with exogenous oxygen to form peroxynitrite, a known impediment to alveolar epithelial cell function. Many cases of pulmonary edema in pregnancy are diagnosed as hydrostatic based on clinical parameters, such as positive maternal fluid balance. In this case, these parameters would have been misleading. Measurement of the protein concentration in the pulmonary edema fluid allowed us to accurately determine that the patient had increased permeability pulmonary edema as the cause of her acute respiratory failure. Sampling of pulmonary fluid can differentiate the type of edema formation and in some cases help to identify mechanisms of acute lung injury.

Adult↗

Prenatal hormonal therapy improves pulmonary compliance in the nitrofen-induced CDH rat model.

Neonates with congenital diaphragmatic hernia (CDH) experience a high mortality despite intensive medical and surgical management. The associated pulmonary hypoplasia is accompanied by an underlying biochemical deficiency that bears similarity to respiratory distress syndrome (RDS) in the premature newborn. Using therapies extrapolated from those used to treat RDS, the authors have previously shown correction of the immature pulmonary biochemical indices in the nitrofen rat CDH model. This study investigates the functional and histological outcome of prenatal hormone therapy on CDH rats. Compared with saline-treated CDH controls, dexamethasone-treated CDH animals achieved significant increases in lung distensibility (P = .0006) and functional residual capacity (P = .004); CDH rats treated with combined dexamethasone and thyrotropin-releasing hormone (TRH) showed improved functional residual capacity (P = .043) and alveolar stability (P = .025); CDH animals treated with TRH alone (TRH-CDH) showed no improvement in any parameter tested. Histologically, the lungs from dexamethasone- and dexamethasone-TRH-treated CDH animals showed changes that included narrow septal walls, increased air saccule size, and thinning of the pulmonary interstitium compared with the lungs of saline or TRH-CDH rats, which were developmentally arrested at the canalicular stage. Lung weights and lung weight-body weights ratios were similar in all CDH rats, confirming that treatment did not impair pulmonary growth. These results support the potential clinical use of prenatal pharmacological therapies to treat human fetuses with prenatally diagnosed CDH.

Animals↗

Importance of preserving the mitral subvalvular apparatus in mitral valve replacement.

BACKGROUND: This clinical study sought to determine whether mitral valve replacement (MVR) with the preservation of both anterior and posterior chordae tendineae (MVR group II) would be more effective on the improvement of left ventricular regional wall motion than MVR with the preservation of posterior chordae tendineae alone (MVR group I). METHODS: Postoperative left ventricular wall motion was analyzed by a centerline method in three groups of MVR--group I (n = 13), group II (n = 15), and repair group (n = 15)--for mitral regurgitation. Shortening fraction of chordal length was determined in 100 chords, and these chords were divided into five regions. RESULTS: The comparison of postoperative versus preoperative shortening fraction among the three groups revealed that postoperative wall motion improved more strikingly at apical and diaphragmatic regions in the MVR group II and repair group in comparison to the MVR group I. The postoperative shortening fraction at the apical region in the MVR group II was significantly increased in comparison to preoperative shortening fraction (preoperative, 3.68% +/- 1.87%; postoperative, 5.38% +/- 2.33%; p < 0.05). However, postoperative shortening fraction in cardiac base was decreased in the MVR group II as well as other two groups. CONCLUSIONS: The MVR with the preservation of both anterior and posterior chordae tendineae contributed to the improvement of left ventricular regional wall motion in the apical and diaphragmatic regions.

Adult↗

Vagal afferent modulation of nociception.

Chemical, electrical or physiological activation of cardiopulmonary vagal (cervical, thoracic or cardiac), diaphragmatic vagal (DVAG) or subdiaphragmatic vagal (SDVAG) afferents can result in either facilitation or inhibition of nociception in some species. In the rat, these effects depend upon vagal afferent input to the NTS and subsequent CNS relays, primarily in the NRM and ventral LC/SC, although specific relay nuclei vary as a function of the vagal challenge stimulus. Spinal pathways and neurotransmitters have been identified for vagally mediated effects on nociception and consistently implicate the involvement of descending 5-HT and noradrenergic systems, as well as intrinsic spinal opioid receptors. Species differences may exist with respect to both the effects of DVAG and SDVAG afferents on nociception and the efficacy of vagal afferents to modulate nociception. However, it is also possible that such differences reflect the modality of noxious input (e.g., visceral versus cutaneous), the type of neuronal activity investigated (e.g., resting versus noxious-evoked), spinal location of recording (e.g., thoracic versus lumbosacral) and/or parameters of stimulation. It is also possible that activation of some vagal afferents is aversive, but whether this contributes to changes in nociception produced by vagal activation has not clearly been established. Finally, the vagal-nociceptive networks described in this review provide a fertile area for future study. These networks can provide an understanding of physiological and pathophysiological peripheral events that affect nociception.

Afferent Pathways↗