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Measurements of ventilatory regulation.

The ventilatory control system, although not yet fully understood, is a complex interaction of volitional and reflex mechanisms extending from the cerebral cortex to receptors in the lungs and chest wall. Measurements of ventilatory control mechanisms can be made at rest, during exercise, during sleep, and during hypercapnic or hypoxic stimuli. Measurements of ventilation, ventilatory pattern, and mouth occlusion pressure at rest provide valuable information on ventilatory control mechanisms; these measurements can be extended by measurements of diaphragmatic EMG (indicating central neural output) and measurements of ventilation and mouth occlusion pressure during CO2 or hypoxic stimulation. Clinical assessment of ventilatory control abnormalities requires an understanding of the basic features of the control system and a logical application of the available tests.

Humans↗

Differential display of genes in normal and hypoplastic fetal murine lungs.

To evaluate lung development at the level of gene expression, a comparison was made between normal and hypoplastic murine fetal lungs by using the mRNA differential display technique. We focused on altered gene expressions at gestational day (Gd) 19 in normal and hypoplastic murine lungs. Hypoplastic fetal lungs were created by gavaging pregnant mice at Gd8 with 25 mg of nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) [1]. Normal as well as gavaged mice were euthanized by an overdose of halothane at Gd19, and fetuses were removed by laparotomy. Lungs were excised and total RNA was extracted from normal and hypoplastic fetal lungs. Differential display technique was carried out using the RNAimage kit (GenHunter Corp., TN). Each reverse transcription and polymerase chain reaction (RT-PCR) was performed using one specific anchor primer H-T11M (5'HindIII-T11A/C/G3') and one arbitrary primer. We have used a total of 3 different anchor primers and 24 arbitrary primers for each sample. There were 20 differentially expressed cDNA clones, either induced, inhibited, enhanced, or reduced in hypoplastic fetal lungs as compared to normal. Of these, one clone (NL2) with reduced expression in Gd19 hypoplastic lungs had 100% homology with mouse nucleosome assembly protein I gene. Another clone (NT5) with induced expression in hypoplastic lungs is an unknown gene. Further, analyses of Northern blots of lungs from various gestational ages showed that the expression of NT5 was induced in hypoplastic lungs at Gd18, whereas in normal lungs it was first expressed at the neonatal stage and was increasingly expressed into adulthood. There is a single hybridized band, approximately 400 bp long for NT5 message. Dexamethasone induced expression of NT5 in normal Gd14 pseudoglandular lungs cultured for 7 days; however, different growth factors did not. Northern blot hybridization of multiple adult mice tissues showed NT5 expression in the lung, intestine, and spleen. The thyromimetic action of nitrofen and the interactive functional pathways of dexamethasone with T3 are known. Therefore, we suggest that the isolation and characterization of NT5 may provide valuable information on the regulation of lung development.

Animals↗

Contribution of rib cage and abdominal movement to ventilation for successful weaning from mechanical ventilation.

In order to test the hypothesis whether the breathing pattern is helpful in predicting weaning outcome in patients being weaned from mechanical ventilation, 38 patients who underwent operation for esophageal cancer were evaluated at weaning from mechanical ventilation (19 unsuccessful weanings, group U, and 19 successful weanings in age-matched patients, group S). Since all patients initially fulfilled our weaning criteria, ventilatory parameters such as tidal volume, respiratory frequency, minute ventilation, and arterial blood gas analysis showed no significant differences between the groups. The breathing pattern was registered quantitatively by means of respiratory inductive plethysmography at 3 cmH2O (0.3 kPa) of CPAP prior to weaning. The contribution of rib cage movement to tidal volume (%RC) was significantly greater in group U than in group S (P < 0.05). Indeed, 84% of the patients in group S showed %RC less than 50%, compared to only 16% of the patients in group U (P < 0.05). The results suggest that the breathing pattern is one important factor in predicting the outcome of weaning in patients after thoraco-abdominal surgery. Diaphragmatic fatigue is suspected to be the mechanism for the increase in the RC component in patients with unsuccessful weaning outcome.

Abdomen↗

Immediate effect of respiratory muscle stretch gymnastics and diaphragmatic breathing on respiratory pattern. Respiratory Muscle Conditioning Group.

We investigated the immediate effect of respiratory muscle stretch gymnastics (RMSG) and diaphragmatic breathing (DB) on the respiratory pattern in patients with chronic obstructive pulmonary disease (COPD). Sixteen patients with COPD (age, 71.3 +/- 3.9 year) were entered in the study. DB was performed for 10 minutes in supine position. For RMSG, 5 patterns were repeated 10 times each. Respiratory variables were measured in sitting position before and after both RMSG and DB, performed in random order, patient to patient, with a 20-minute washout period in-between. After RMSG, but not after DB, there was a significant overall prolongation in expiratory time. After DB, but not after RMSG, there was an overall decrease in minute ventilation, carbon dioxide output, respiratory gas exchange ratio, end tidal O2 fraction, end tidal CO2 fraction and tidal diaphragmatic volume. The results suggest that RMSG may have a beneficial effect on the respiratory pattern. On the other hand, DB may provoke post-hyperventilation hypoxemia.

Aged↗

New neonatal extracorporeal membrane oxygenation circuit with a self-regulating blood pump.

BACKGROUND: Because a roller pump used in a conventional extracorporeal membrane oxygenation (ECMO) circuit with a roller pump cannot change the output automatically according to the venous return, ECMO management requires considerable personnel to prevent serious mechanical complications. An automatic blood pump will make ECMO less laborious and safer. METHODS: Takagi's self-regulating blood pump was modified for neonatal ECMO. The new ECMO circuit was tested in a simulation circuit, in puppies, and in two neonates clinically. Self-regulation of the pump was studied in response to various hemodynamic conditions. RESULTS: The priming volume including a membrane lung and a heat exchanger was about 90 ml. The maximum flow was 700 ml/min in the simulation circuit, 101 ml/min/kg in puppies, and 113 and 135 ml/min/kg in two newborns, respectively. ECMO flow was self-regulating and stable in response to hemodynamic changes. The blood pumps remained functional for more than 400 hours in puppies and 67 and 149 hours in the two newborns, respectively. CONCLUSIONS: The new automatic ECMO circuit is more reliable and requires less personnel than a conventional ECMO circuit.

Animals↗

Intraoperative and postoperative esophageal manometric findings with Collis gastroplasty and Belsey hiatal hernia repair for gastroesophageal reflux.

The combination of a Collis gastroplasty with a Belsey Mark IV fundoplication has proved clinically effective in the management of certain patients with complications of gastroesophageal reflux. The present study measured the effect of gastroplasty and Belsey repair on intraluminal pressure changes in the gastroplasty and lower esophagus. Manometric studies were performed preoperatively, intraoperatively, and postoperatively. In each case the gastroplasty segment of the esophagus was found to function as a high pressure zone (HPZ). The pressure in this zone further increased following the fundoplication. It could be diminished with intravenous administration of Buscopan and augmented with intravenously given pentagastrin. The original lower esophageal sphincter in most instances was included in the upper segment of the gastroplasty tube, but the entire length of the gastroplasty tube functioned as an HPZ, and pressures in the tube were considerably higher than those originally present in the lower esophageal sphincter. These studies provide a physiological rationale for the effectiveness of gastroplasty and fundoplication.

Animals↗

Uncut Collis-Nissen fundoplication: learning curve and long-term results.

BACKGROUND: Between September 1985 and July 1990, the first 100 consecutive patients (50 female and 50 male) undergoing primary uncut Collis-Nissen fundoplication performed by one surgeon were reviewed. METHODS: Median age was 62 years and ranged from 19 to 89 years. Indications for repair included gastroesophageal reflux in 56 patients, obstructive symptoms in 34, and a combination of both in 10. An upper gastrointestinal endoscopy was performed in 99 patients; all were abnormal. Esophagitis was documented in 53 patients, large diaphragmatic hernia in 36, stenosis in 18, "Cameron's erosions" in 17, Barrett's disease in 13, and other findings in 9 patients. An abnormal upper gastrointestinal series was demonstrated in 96 of 97 patients evaluated. Motility studies were performed in 95 patients, and 11 had abnormal peristalsis. All procedures were performed through a left thoracotomy. RESULTS: Complications occurred in 23 patients and included respiratory failure in 6, atrial fibrillation in 3, atelectasis in 3, pneumonia in 2, myocardial infarction in 2, and chylothorax, severe dysphagia, early breakdown of repair, cardiac tamponade, hematuria, spinal headache, and intraoperative perforation by dilator in 1 each. There were 2 postoperative deaths, both cardiac in origin. Median hospitalization was 8 days (range, 6 to 76 days). The first 25 patients had 10 complications (40%) and 2 deaths (8%). The remaining 75 patients had 13 complications (17%) and no deaths (mortality, p = 0.06; morbidity, p = 0.03). Follow-up was complete in all patients for a median of 100 months (range, 3 to 138 months). Eighty-six of the 98 operative survivors are currently alive. At last follow-up, excellent functional results were observed in 58 patients (59%), good in 24 (25%), fair in 8 (8%), poor in 7 (7%), and unknown in 1 (1%). CONCLUSION: We conclude that the uncut Collis-Nissen fundoplication provides good to excellent long-term results in 84% of patients. Operative mortality and morbidity is acceptable but is associated with a learning curve.

Adult↗

Partial liquid ventilation and nitric oxide in congenital diaphragmatic hernia.

PURPOSE: In congenital diaphragmatic hernia (CDH) there is immature lung development with a resulting clinical picture of pulmonary hypoplasia, surfactant deficiency, and pulmonary hypertension. Pulmonary hypoplasia and surfactant deficiency both have been successfully treated using partial liquid ventilation (PLV). Pulmonary hypertension associated with CDH has proven difficult to treat, but inhaled nitric oxide, which is a potent highly selective pulmonary vasodilator, may have potential. The aim of this study was to assess PLV in CDH and to document the effect of nitric oxide when administered through perfluorocarbon. METHODS: This study using the lamb CDH model consisted of two groups; a conventional mechanically ventilated (CMV) group and a PLV group. At 1 and 3 hours, nitric oxide (80 ppm) was given for 15 minutes. Data collected included blood gases, pulmonary function tests, pulmonary and systemic blood pressure. RESULTS: After 30 minutes of ventilation, blood gases in the PLV group were all significantly improved (P < .001): pH, CMV 6.92 +/- 0.15 versus PLV 7.24 +/- 0.11; P(CO2), CMV 139 +/- 26 mmHg versus PLV 52 +/- 11 mmHg; P(O2), CMV 26 +/- 15 mmHg versus PLV 184 +/- 60 mmHg. In addition, there was a significant increase in dynamic compliance and a reduction in pulmonary hypertension. Nitric oxide was only efficacious in the PLV group, causing a further increase in oxygenation and a decrease in pulmonary hypertension. These effects were reversed when the nitric oxide was stopped. CONCLUSION: This study shows that PLV both improves gas exchange and pulmonary mechanics in CDH and allows the effective delivery of nitric oxide to reduce the pulmonary hypertension associated with CDH.

Animals↗

Coeliac artery aneurysm: aorto-hepatic artery reconstruction.

Aneurysms of the coeliac axis are rare. Up to 1997, 137 cases had been reported. Here we present a coeliac aneurysm which involved the origin of the splenic, left gastric, and common hepatic arteries. After making a midline incision, infra-diaphragmatic control of the aorta was obtained. The aorta was clamped for 25 minutes to resect the aneurysm. The defect at the origin of the coeliac axis was closed with 1.5 cm PTFE patch. The distal segments of the splenic and left gastric arteries were ligated. A 6-mm ringed PTFE graft was interposed between the infra-renal aorta and the proper hepatic artery. The control arteriogram showed a good arterial flow. The patient recovered uneventfully after surgery with normalisation of hepatic function.

Adult↗

[Surfactant replacement therapy]

OBJECTIVE: To analyze and update information about surfactant therapy replacement in newborns with lung diseases. SOURCES: Literature review, including textbooks, meta-analyses, prospective, randomized controlled trials, retrospective assessments and case studies. Literature was reviewed based on the authors clinical and scientific experience regarding surfactant replacement therapy in neonatal lung diseases. SUMMARY OF THE FINDINGS: Surfactant replacement therapy for the neonatal respiratory distress syndrome improves respiratory function, and reduces the need for oxygen supplementation and pressure support ventilation, in addition to minimizing the air leak syndrome. However, the use of surfactant did not prevent the occurrence of other intercurrent diseases such as patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, and bronchopulmonary dysplasia. The surfactant treatment decreased neonatal mortality up to 40%. The effectiveness of exogenous surfactant on other respiratory diseases with surface film dysfunction, such as meconium aspiration syndrome, pneumonia, acute respiratory distress syndrome and congenital diaphragmatic hernia has not yet been widely accepted. CONCLUSIONS: Surfactant replacement is now considered the standard treatment for newborns with respiratory distress syndrome. We hope that, in the future, new synthetic surfactant preparations will be more effective in treating other infant respiratory diseases.

Journal Article↗

Does the crural diaphragm share in the contractile activity of the costal diaphragm? The concept of an "autonomous esophageal crus" and its role in esophageal competence.

BACKGROUND: We investigated the hypothesis that the esophageal crus (EC, part of the crus surrounding the esophagus) is an "individual muscle" and does not share in the contractile activity of the costal diaphragm (CD). MATERIAL/METHODS: The electric activities of the EC and the costal diaphragm (CD) were recorded in 21 subjects (12 men, 9 women, aged 41.6+/-10.4 years) scheduled for laparotomy. One needle electrode was introduced into the EC, one into each vertebral crus (VC), and one in the CD. Recording was performed before and after diaphragmatic paralysis by curarization. While the diaphragm was paralyzed, the responses of the EC and the 2 VCs to CD stimulation were registered. RESULTS: The CD had significantly higher resting motor unit action potentials (MUAPs) than the EC and the 2 VCs (p<0.05), and the EC higher MUAPs than the 2 VCs (p<0.05). During diaphragmatic contraction on inspiration or by stimulation (5 square pulses, 1 ms apart, threshold 32.2+/-6.3 mA), the MUAPs of the CD increased significantly (p<0.01), while those of the EC or VCs exhibited no significant change (p<0.05). CONCLUSIONS: The current findings suggest that the EC is an autonomous muscle which does not share in the contractile activity of the CD. The EC seems to be essentially involved in the competent mechanism of the lower esophagus and has no role in respiratory function.

Abdominal Muscles↗

[Physiological basis of fetal and neonatal circulation].

The extremely reduced nature of the pulmonary circulation, the parallel arrangement of the right and left sides of the heart, and the mixture of oxygenated umbilical blood with the rest of the venous return in the right atrium endow the foetal circulation with its "relatively protected" nature. Thus the majority of cardiac and pulmonary malformations have no effect or cause only minor circulatory disturbances. The transfer of respiratory function from the placenta to the lungs which becomes necessary as soon as the cord is clamped is a highly disturbing event. The pulmonary circulation must be established, the communications of foetal life close (Botal's foramen, ductus arteriosus), and the right and left heart function in series. Such adaptations, certain of which are essential to immediate survival, may require several weeks before completion. Any disease in the newborn, congenital or acquired, respiratory, circulatory, metabolic or other, is accompanied by numerous interwoven consequences. In particular, return to a foetal type circulation by increase or absence of pulmonary resistances could induce a right-left shunt through a fossa ovale which is only asking to open, or even through a ductus arteriosus which is only asking to reopen. Congenital diaphragmatic hernia is no exception is no exception to this rule.

Blood Circulation↗

[Formation of mitochondrial reticulum in the diaphragmatic muscle in rat ontogeny].

The development of a complex system of mitochondrial reticulum of the rat diaphragm muscle fibers proceeds in several steps during ontogenesis. At first (19 day-old embryo and early postnatal period) the mitochondria grow in the longitudinal (with respect to the muscle fiber) direction, being located in the intermyofibrillar spaces. On the 9-10th day after birth there appear mitochondrial processes perpendicular to the long axis of muscle fiber at the levels of isotropic myofibrillar discs. These processes are later replaced by the branched giant mitochondria lying as if in floors across the muscle fiber. All mitochondria are interconnected by means of special contacts in a single system of mitochondrial reticulum. The functional role of complex mitochondria in the cross-striated muscle is discussed.

Animals↗

Hypoxic effects on exercise-induced diaphragmatic fatigue in normal healthy humans.

We examined the effects of hypoxia on exercise-induced diaphragmatic fatigue. Eleven subjects with a mean maximal O2 uptake of 52.4 +/- 0.7 ml.kg-1.min-1 completed one normoxic (arterial O2 saturation 96-94%) and one hypoxic (inspiratory O2 fraction = 0.15; arterial O2 saturation 83-77%) exercise test at 85% maximal O2 uptake to exhaustion on separate days. Supramaximal bilateral phrenic nerve stimulation (BPNS) was used to determine the pressure generation of the diaphragm pre- and postexercise at 1, 10, and 20 Hz. There was increased flow limitation during hypoxic vs. normoxic exercise. There was a decrease in hypoxic exercise time (normoxic 24.9 +/- 0.7 min vs. hypoxic 15.8 +/- 0.8 min; P < 0.05). After exercise the BPNS transdiaphragmatic pressure (Pdi) was significantly reduced at 1 and 10 Hz after both exercise tests. The BPNS Pdi was recovered to control values by 60 min postnormoxic exercise but was still reduced 90 min posthypoxic exercise. The mean percent fall in the stimulated BPNS Pdi was similar (normoxic -24.8 +/- 4.7%; hypoxic -18.8 +/- 3.0%) after both exercise conditions. Experiencing the same amount of diaphragm fatigue in a shorter time period in hypoxic exercise may have been due to 1) the increased expiratory flow limitation and diaphragmatic muscle work, 2) decreased O2 transport to the diaphragm, and/or 3) increased levels of circulating metabolites.

Adult↗

Relationship of a hiatal hernia to the function of the body of the esophagus and the gastroesophageal junction.

One hundred two patients referred to our Esophageal Function Laboratory without endoscopic evidence of esophagitis were divided into two groups on the basis of the presence of a hiatal hernia on endoscopic examination. Fifty-three patients had a hiatal hernia and 49 did not. Both groups and 30 normal volunteer subjects had esophageal manometry and 24 hour esophageal pH monitoring. The incompetency of the cardia in patients with a hiatal hernia was dependent upon loss of components responsible for the antireflux mechanism, mainly a decrease in distal esophageal sphincter pressure and a decrease in the length of the sphincter exposed to the positive-pressure environment of the abdomen. These deficiencies were not related to the presence of a hiatal hernia and were similar to those of patients with an incompetent cardia without a hiatal hernia. Patients with a hiatal hernia and an incompetent cardia had significantly more esophageal exposure to refluxed acid than without a hiatal hernia. On the basis of the number of reflux episodes that lasted 5 minutes or longer and radioisotope transit studies, this increased acid exposure was due to both a loss of competency of the cardia and poor esophageal clearance secondary to the presence of a hiatal hernia. Reduction of the hernia and anchoring the distal esophagus into the abdomen not only may improve the antireflux mechanism, but corrects the clearance abnormality as well. The presence of a hiatal hernia has a detrimental effect on the clearance function of the body of the esophagus and may aggravate the effects of gastroesophageal reflux due to an incompetent cardia.

Adolescent↗

Respiratory response and ventilatory muscle recruitment during arm elevation in normal subjects.

Despite the fact that the arms are used extensively in daily life and that some of the muscles of the shoulder girdle share both a respiratory and a positional function for the arms, surprisingly little is known about the respiratory response to unsupported upper extremity activity. To determine the respiratory consequences of simple arm elevation during tidal breathing, we measured minute ventilation (VE), tidal volume (VT), respiratory rate (f), heart rate (HR), oxygen uptake (VO2), and carbon dioxide production (VCO2) in 22 normal subjects seated with arms elevated in front of them to shoulder level (AE) for 2 min and down at the sides (AD) for the same time period. The sequence was randomized. Compared with AD, during AE there were significant increases in VO2 (336 +/- 18 vs 289 +/- 14 ml/min, p less than 0.001), VCO2 (315 +/- 23 vs 245 +/- 16 ml/min, p less than 0.001), HR (84 +/- 6 vs 73 +/- 4 beats/min, p less than 0.05), VE (11.5 +/- 0.9 vs 9.3 +/- 0.6 L/min, p less than 0.001), and VT (868 +/- 66 vs 721 +/- 48 ml, p less than 0.001). In 11 subjects, breath-by-breath metabolic and ventilatory parameters were studied with AD for 2 min, AE for 2 min, and with AD for 3 min while also recording gastric (Pg), pleural (Ppl), and transdiaphragmatic pressures (Pdi). With AE, there was a significant increase in Pg at end inspiration (PgI, 15.4 +/- 3.2 vs 11.9 +/- 2.7 cm H2O, p less than 0.01) and in Pdi (26.5 +/- 3.4 vs 21.4 +/- 2.4 cm H2O, p less than 0.01) with no change in Pg at end expiration (PgE) or in Ppl. The increases in VO2, VCO2, VE, and VT during arm elevation persisted for 2 min after arm lowering, whereas Pgi and Pdi abruptly dropped as the arms were lowered. We conclude that simple arm elevation during tidal breathing results in significant increases in metabolic and ventilatory requirements. These increased demands are associated with higher PgI and Pdi suggesting an increased diaphragmatic contribution to the generation of ventilatory pressures. The sudden drop in Pg with arm lowering indicate a change in ventilatory muscle and or torso recruitment independent of the metabolic drive and ventilatory needs. These findings may help explain the limitation that has been reported in some normal subjects and in many patients with lung disease during unsupported upper extremity activity.

Adult↗

A procedure for chronic recording of diaphragmatic electromyographic activity.

A simple procedure for recording of diaphragmatic electromyographic activity in awake, freely behaving animals is described. This procedure produces highly stable recording of muscle activity for very long periods. Because of its ease of use, the procedure has become the technique of choice for acute recording in our laboratories as well. The present procedure can also be adapted for chronic recording of electromyographic activities from nonrespiratory muscles. This option thus offers a variety of applications to those involved in investigations into the central neuromotor control of movement, pattern generation and autonomic functions.

Animals↗