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The effects of the patent ductus arteriosus on diaphragmatic blood flow and function.

Decreased diaphragmatic blood flow (Qdi) is associated with decreased contractility in adult animals. To see whether the decrease in Qdi associated with a patent ductus arteriosus was associated with a decrease in diaphragmatic contractility (Pdi), we prepared 11 near-term fetal lambs by infiltrating the ductus with formalin and placing a snare around it to regulate its patency. The lambs (with open chest) were delivered and mechanically ventilated, and the phrenic nerves and diaphragm were paced (using transvenous wires) at rates of 20/min, 60/min, and 100/min (Inspiratory time/total respiratory cycle time = 0.5) for 7-min contraction periods after 30-min recovery periods. Qdi was measured with radiolabeled microspheres at the end of each contraction period. Diaphragmatic performance was determined by comparing Pdi at the start (Pdi-start) and end (Pdi-end) of the contraction period. When the ductus was closed, Qdi increased 6.9-fold at 20/min and 9.8-fold at 100/min (compared with Qdi at rest). Pdi-end was less than Pdi-start at all contraction rates, but the reduction was significantly greater at 100/min (Pdi-end/Pdi-start: 0.80 +/- 0.10 at 20/min; 0.67 +/- 0.17 at 100/min). Pdi-start also decreased with increasing rates of contraction. When the ductus was open, the left-to-right shunt was 64 +/- 11% of left ventricular output. Qdi in the unpaced diaphragm was significantly reduced (open 4.0 +/- 3.8 versus closed, 7.4 +/- 2.4 mL/min/100 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure.

We studied the effects of hypophosphatemia on diaphragmatic function in eight patients with acute respiratory failure who were artificially ventilated. Their mean serum phosphorus level was 0.55 +/- 0.18 mmol per liter (normal value, 1.20 +/- 0.10). The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic function was evaluated in each patient before and after correction of hypophosphatemia, which was achieved by administration of 10 mmol of phosphorus (as KH2PO4) as a continuous infusion for four hours. After phosphate infusion, the mean serum phosphorus level increased significantly (1.33 +/- 0.21 mmol per liter, P less than 0.0001). The increase in serum phosphorus was accompanied by a marked increase in the transdiaphragmatic pressure after phrenic stimulation (17.25 +/- 6.5 cm H2O as compared with 9.75 +/- 3.8 before phosphate infusion, P less than 0.001). Changes in the serum phosphorus level and transdiaphragmatic pressure were well correlated (r = 0.73). These results strongly suggest that hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure, and they emphasize the importance of maintaining normal serum inorganic phosphate levels in such patients.

Acute Disease

An electrophysiological analysis of sleep and respiration of rats breathing different gas mixtures: diaphragmatic muscle function.

The effects of breathing 21% O2, 21% O2 + 5% CO2, 10% O2 + 4% CO2 and 10% O2 on the sleep-waking rhythm, respiratory rate, diaphragmatic EMG, inspiratory (Ti) and expiratory (Te) times were studied in rats. They carried chronically implanted electrodes to permit polygraphic recordings of the ECoG, EOG and dorsal neck and integrated diaphragmatic EMG activity. Average respiratory rates, independent of state of consciousness varied depending on the gas mixture breathed. Sleep-waking times, expressed as percentages, were determined as a function of the gas mixture breathed. Oxygen deficiency caused PS deprivation which was partially alleviated by the addition of 4% CO2. Diaphragmatic EMG activity decreased during PS when rats breathed gas mixtures rich in CO2 but increased when they breathed 10% O2. In general, at a given frequency of breathing, Ti was shorter during PS than during SWS except when rats breathed 10% O2. It is concluded that: (1) regardless of the state of consciousness hypoxia is a more potent stimulus of respiratory rate than hypercapnia, (2) diaphragmatic effort is reduced when rats breathe CO2 enriched gas mixtures but is increased by hypoxia due to changes in upper airway resistance, and (3) low O2 content of an inspired gas disrupts the inspiratory and expiratory off-switch mechanisms, this disruption being prevented by the addition of CO2.

Animals

Successful reinnervation of the diaphragm after phrenic nerve transection.

A 16-month-old infant presented with bilateral diaphragmatic paralysis and respiratory failure after removal of a thoracic teratoma. Right diaphragmatic function recovered after end-to-end anastomosis of a transected phrenic nerve. We conclude that phrenic nerve repair can restore diaphragmatic function and should be attempted in selected cases of diaphragmatic paralysis due to phrenic nerve injury.

Diaphragm

Inspiratory muscle function with restrictive chest wall loading during exercise in normal humans.

The effects of selective restriction of rib cage (Res,rc) and abdominal wall (Res,ab) movements on endurance of short-term constant-load heavy exercise and on diaphragmatic function during such exercise were examined in five normal young men. An inelastic surgical corset was used to achieve Res,rc and Res,ab. Subjects exercised on a cycle ergometer at 80% of their maximum power output to exhaustion on three occasions: with Res,rc, with Res,ab, and without restriction of chest wall movements (control). Transdiaphragmatic (Pdi), esophageal, and gastric pressures were measured. Electromyogram of the diaphragm was recorded by an esophageal electrode, and the ratio of the power content of a high-frequency to low-frequency band (H/L ratio) was measured. In addition, maximum Pdi (Pdimax) pre- and immediately postexercise was recorded. Res,rc was associated with a shorter endurance time, a progressive decline of the H/L ratio, and a significant reduction of Pdimax postexercise, whereas no such changes were found with Res,ab. We conclude that diaphragmatic function was well defended with abdominal wall loading, whereas limitation of rib cage expansion reduced diaphragmatic endurance during exercise. The diaphragmatic tension-time index (TTdi) in exercise was always less than the critical value of 0.15 found by Bellemare and Grassino (J. Appl. Physiol. 53: 1190-1195, 1982) when subjects inspired against large resistive loads at normal minute ventilations. We suggest that the higher inspiratory flow rate (P less than 0.05) and breathing frequency (P less than 0.05) account for the occurrence of diaphragmatic fatigue in exercise with Res,rc when the TTdi was 0.06 +/- 0.02.

Abdominal Muscles

Plication of the diaphragm for symptomatic phrenic nerve paralysis.

Paralysis of the diaphragm in infants may produce severe respiratory difficulty because of the paradoxic motion of the affected diaphragm and shift of a mobile mediastinum to the contralateral side. Six infants with diaphragmatic paralysis and severe respiratory distress underwent plication of the diaphragm by a simple technique. Five of the six infants had significant improvement in respiratory effort and were ultimately weaned from ventilatory support. One patient with bilateral paralysis had only minimal improvement. Diaphragmatic function returned in two patients after plication. Plication of the diaphragm is a safe and useful procedure to improve ventilation in infants with a paralyzed diaphragm. Since this technique does not prevent return of diaphragmatic function, it should be employed prior to the development of sequelae of prolonged assisted ventilation and sooner if the phrenic nerve is permanently injured.

Diaphragm

Respiratory muscle function and dyspnea in patients with chronic congestive heart failure.

BACKGROUND: Patients with heart failure (HF) frequently experience exertional dyspnea. Using near-infrared spectroscopy, we have previously demonstrated accessory respiratory muscle deoxygenation during exercise in these patients by monitoring changes in light absorption at 760-800 nm. METHODS AND RESULTS: To investigate whether low-frequency respiratory muscle fatigue occurs, we performed supramaximal bilateral transcutaneous phrenic nerve stimulation before and after maximal bicycle exercise in 10 patients with HF (age, 62 +/- 10 years; ejection fraction, 18 +/- 7%) and six normal subjects (age, 50 +/- 8 years). Maximal rates of contraction and relaxation, peak twitch tension, and maximal transdiaphragmatic pressure (Pdi) were derived before and after exercise from analysis of six to 12 twitches obtained at functional residual capacity. Pdi, time in inspiration (Ti), time per breath (TTOT), respiratory gases, ratings of perceived dyspnea and fatigue, and 760-800 nm near-infrared spectroscopy absorbency changes of the serratus anterior muscle were measured throughout exercise. The tension time index (TTdi) of the diaphragm was derived. In both normal and HF subjects, all parameters of diaphragmatic function (i.e., maximal rates of contraction and relaxation, peak twitch tension, and maximal Pdi) were unchanged before and after exercise. Mean Pdi was comparable at rest (normal, 3.7 +/- 1; HF, 5.8 +/- 2.9 cm H2O; p = NS) but significantly greater in patients with HF at peak exercise (normal, 12.1 +/- 3; HF, 18.3 +/- 6.6 cm H2O; p less than 0.05). Ti/TTOT of both groups was similar at rest and throughout exercise. TTdi was significantly greater at rest (normal, 0.01 +/- 0.01; HF, 0.03 +/- 0.02; p less than 0.05) and at peak exercise (normal, 0.03 +/- 0.02; HF, 0.10 +/- 0.03; p less than 0.04) in patients with HF. Significant accessory respiration muscle deoxygenation was noted only in patients with HF (peak exercise; normal, -1 +/- 13; HF, 28 +/- 15 arbitrary units; p less than 0.01). Linear correlation analysis was performed between ratings of perceived dyspnea and parameters of pulmonary and diaphragmatic function. Significant correlations were observed between ratings of perceived dyspnea and maximal inspiratory and expiratory pressure, the TTdi of the diaphragm, near-infrared absorption changes, and forced expiratory volume in 1 second (FEV1) (all r greater than 0.5; p less than 0.05). Thus, respiratory muscle strength, work, and oxygenation were significantly correlated with the degree of dyspnea. CONCLUSIONS: We conclude that low-frequency diaphragmatic muscle fatigue does not occur despite accessory respiratory muscle deoxygenation during exercise in patients with HF. However, diaphragmatic work as assessed by the TTdi is dramatically increased in patients with HF and approaches levels previously shown to generate fatigue. The sensation of dyspnea appears closely related to respiratory muscle function.

Aged

Acute supine respiratory failure due to bilateral diaphragmatic paralysis.

This report documents the first known case of bilateral diaphragmatic paralysis following blunt trauma to the chest. The important role of diaphragmatic function in maintaining ventilation, particularly with the patient in the supine position, is illustrated by the reduced total lung capacity, functional residual capacity, and vital capacity. Severe hypoxemia with the patient in the supine position, was markedly improved by elevation of the patient to 30 degree and was further improved by sitting the patient upright. Following an initial period of acute respiratory failure, the patient was managed acceptably by maintaining an elevated position for sleeping until diaphragmatic function returned, about nine months after the injury.

Accidents, Traffic

Effect of halothane on diaphragmatic muscle function in pentobarbital-anesthetized dogs.

The mechanism underlying the decrease in minute ventilation (VE) observed under halothane anesthesia was investigated in nine spontaneously breathing dogs. Anesthesia was induced with pentobarbital sodium and was maintained with halothane. Inspired fraction of halothane (FIhal) was increased every 30 min, from 0.005 to 0.02. VE decreased from 8.1 +/- 0.9 to 4.8 +/- 0.4 l . min-1 (P less than 0.001), as FIhal increased from 0 to 0.02. This resulted from a decrease in both mean inspiratory flow (VT/TI) and the duty ratio (TI/TTOT). Transdiaphragmatic pressure (Pdi) and the integrated electrical activity of both hemidiaphragms (Edi) were measured during normal breathing, and during breathing against closed airways (P0di, E0di), in order to obtain an index of the inspiratory neuromuscular output of the diaphragm. With increasing FIhal, there was a significant decrease in Pdi, P0di, Edi, and E0di. The authors measured Pdi and Edi generated during supramaximal stimulation of the two phrenic nerves (PSdi, Esdi) at frequencies of 10, 20, 50, and 100 Hz, in order to eliminate in this decrease the role played by a decrease in the neural drive to breathing. PSdi and ESdi decreased significantly with increasing FIhal, and had not returned to the control values 30 min after discontinuation of halothane administration. The authors conclude that, in pentobarbital-anesthetized dogs, halothane is responsible for a diaphragmatic dysfunction, which may be located either at the neuromuscular junction, on the contractile processes of the muscle, or on both, and for a decrease in the activation time of the inspiratory muscles. Both of these effects contribute to the decrease in VE observed under halothane anesthesia.

Anesthesia

Influence of ruminal insufflation on pulmonary function and diaphragmatic electromyography in cattle.

In 8 healthy, awake cows with permanent cannulated ruminal fistulas and carotid artery loops, respiratory mechanics, ventilation, and diaphragmatic electrical activity were studied before and during stepwise insufflation of the rumen with air pressure to 40 mm of Hg. We found that ruminal insufflation increased intraperitoneal, intrapleural, and transdiaphragmatic pressures and decreased lung volume and lung compliance. In individual cows with rumen insufflation there was an increase in pulmonary resistance, but this trend was not significant in the group. Peak expiratory flow rate was increased and peak inspiratory flow rate was unchanged. Inspiratory duration (Ti) decidal volume decreased slightly, breathing frequency decreased markedly, and minute volume decreased. When intraruminal pressure reached 40 mm of Hg, arterial partial pressure of carbon dioxide (PaCO2) increased (P less than 0.01) and that of oxygen (PaO2) decreased (P less than 0,01) and arterial blood pH decreased (P less than 0.02). Diaphragmatic electromyographic activity was increased, but mechanical effectiveness of the diaphragm was reduced at increased intraruminal pressures.

Animals

Diaphragmatic performance during recovery from acute ventilatory failure in Guillain-Barré syndrome and myasthenia gravis.

Diaphragmatic muscle performance during acute ventilatory failure due to Guillain-Barré syndrome and myasthenia gravis was assessed to evaluate (1) diaphragmatic function during weaning from ventilatory support and (2) diaphragmatic tension-time integral (TTdi) during ventilatory failure. We used a multilumen nasogastric tube and a pneumotachograph to measure transdiaphragmatic pressure per breath (Pdi), maximum transdiaphragmatic pressure (Pdimax), tidal volume (VT), and inspiratory time fraction during 74 spontaneous breathing trials in nine patients. Diaphragmatic performance was poor in all patients. The Pdi, Pdimax, and VT improved significantly, but values for Pdi and Pdimax remained low even after weaning. Improvement in Pdimax was the best predictor of recovery (r = 0.48; p less than 0.001). Maximal inspiratory force correlated with Pdimax (r = 0.48; p less than 0.005), but FVC did not. The TTdi rarely exceeded the expected fatigue threshold of 0.15 in spite of the patient's inability to sustain ventilation. Although our patients demonstrated diaphragmatic weakness, TTdi did not demonstrate diaphragmatic fatigue.

Acute Disease

Effects of digoxin on diaphragmatic strength generation in patients with chronic obstructive pulmonary disease during acute respiratory failure.

We studied the effects of digoxin, a compound that has an inotropic effect on the myocardium, on diaphragmatic function in 8 patients with chronic obstructive pulmonary disease. All the patients were in acute respiratory failure and were artificially ventilated. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. The latter were stimulated before and at 45 and 90 min after administration of digoxin (0.02 mg/kg infused for 10 min). In all the patients, cardiac output was measured by the thermodilution technique using a Swan-Ganz catheter placed in the pulmonary artery. Arterial blood gases and pH were maintained within normal range by mechanical ventilation. In all the patients, digoxin plasma levels reached the therapeutic range (mean values, 2.82 +/- 0.17 and 2.90 +/- 0.20 nmol/L at 45 and 90 min, respectively) after digoxin administration. Diaphragmatic strength improves significantly after digoxin administration, the transdiaphragmatic pressure for an identical phrenic stimulation increasing by 19.5% (p less than 0.001) on the average. This increase was noted 45 and 90 min after digoxin administration. We conclude that digoxin has a potent effect on diaphragmatic strength generation that may be beneficial in patients with chronic obstructive pulmonary disease during acute respiratory failure. Furthermore, this inotropic positive effect of digoxin on the diaphragm, as previously observed for the myocardium, emphasizes the similarities between these 2 contractile tissues.

Action Potentials

Thoracoabdominal motion in chronic obstructive pulmonary disease.

Studies of thoracoabdominal motion using the respiratory magnetometer were performed in 30 patients with chronic obstructive pulmonary disease. Volume equivalency of thoracic and abdominal deflections was established by using the concepts and methods developed by Konno and Mead. Twenty patients were ambulatory, although disabled, and 10 were in acute respiratory failure and were studied in a respiratory intensive care unit. Five of 20 ambulatory patients and 8 of 10 patients in acute respiratory failure showed inward abdominal motion coincident with outward rib cage motion during inspiration, suggesting ineffective diaphragmatic function. This pattern of thoracoabdominal motion was identical to that seen in 2 high quadriplegics with diaphragmatic paralysis when they were breathing entirely with their neck muscles. Inspiratory ascent of the diaphragm was confirmed fluoroscopically in 3 of the 5 ambulatory patients. Patients showing this pattern were generally severely disabled and had the largest residual volumes. Two abnormal patterns of thoracoabdominal motion were observed during the performance of maximal voluntary ventilation in the ambulatory patients. The first, seen in 9 of 20 patients, was characterized by reciprocal or paradoxical motion of rib cage and abdomen, with increase in rib cage volume associated with decrease in abdominal volume during inspiration. The second pattern, seen in 5 of 20 patients, showed complete disorganization of rib cage and abdominal motion, with no consistent or reproducible pattern. Thus, a significant proportion of patients with disabling chronic obstructive pulmonary disease show abnormalities in thoracoabdominal motion that are observable with the respiratory magnetometer and ofter by simple inspection. Most of these abnormalities suggest malfunction of respiratory muscles, particularly the diaphragm.

Abdomen

Clinical and physiologic evaluation of respiratory muscle function.

The ventilatory muscles are of primary importance in the maintenance of ventilation. This rather complex system of muscles centers around the diaphragm. As diaphragmatic function becomes compromised with the progression of different lung diseases, the participation of other muscles becomes necessary. This is clinically manifested by the recruitment of many of these muscles even during quiet breathing. The use of simple questions during a medical history, determination of the respiratory rate, assessment of the pattern of breathing, and observation of thoracoabdominal movements are helpful in the initial evaluation. Measurement of the FVC, lung volumes, and tidal breathing help direct attention to more specific investigation of the ventilatory muscles. Decreased respiratory muscle strength can be confirmed by measurement of PImax and PEmax. Decreased respiratory muscle endurance can be readily ascertained by measuring the MVV. Use of these simple techniques, available in most laboratories, is appropriate for initial evaluation and establishing a diagnosis. The additional measurements of esophageal and gastric pressures have added a new dimension to the study of the diaphragm; these techniques, however, remain a research tool.

Humans

Effects of aminophylline on diaphragmatic dysfunction after upper abdominal surgery.

The effects of upper abdominal surgery on diaphragmatic function were studied in eight supine patients before and after administration of aminophylline. Changes in pleural (delta Ppl) and gastric pressure (delta Pga) swings were measured with balloon catheter systems. Transdiaphragmatic pressure change (delta Pdi) was calculated as the difference delta Pga-delta Ppl. The ratio delta Pga/delta Pdi, used as an index of the diaphragmatic contribution to the quiet breathing process, decreased significantly as early as 1 h after operation without any further change throughout the 6-h period studied. Administration of aminophylline (6 mg/kg), six hours postoperatively, produced a significant increase in this diaphragmatic index. These data indicate that the early reduced diaphragmatic activity, after upper abdominal surgery, partially may be reversed by administration of aminophylline. The mechanism of its action may involve central nervous stimulation and/or a direct inotropic effect on diaphragmatic muscle. Further studies are needed to evaluate if the correction of altered diaphragmatic motion by aminophylline improves postoperative lung function.

Abdomen

[Effect of peritoneal dialysis on respiratory function in patients with chronic renal failure].

In 17 patients with end stage renal failure the effect was studied of a single peritoneal dialysis on the respiratory function, in the sitting and the recumbent position of the body. After the infusion of 2 liters of the dialysis fluid into the peritoneal cavity arterial PaO2 fell as well as the functional residual capacity, but the alveolar/arterial oxygenation difference (A-alpha)O2 rose. The most marked changes accompanied by dyspnea occurred in most patients in the sitting position. The inspiratory residual volume (IRV) increase reflects a better diaphragmatic function. The usefulness of aminophylline is discussed which not only dilates the bronchi but also improves the contractibility of the diaphragmatic muscle.

Adult

Prosthetic materials and muscle flaps in the repair of extensive diaphragmatic defects: an experimental study.

Relative merits of three methods of diaphragmatic hernia repair were evaluated in growing animals. Twenty-five puppies underwent laparotomy. In four controls, the left hemidiaphragm was incised and sutured primarily. In the remaining dogs, it was partially resected sparing the phrenic nerve. The defects were repaired in six with silastic sheeting, in eight with polytetrafluoroethylene (PTFE; trademark, Gore-Tex), and in seven with a thoracoabdominal muscle flap. Dogs were killed at 1, 4, and 7 months for gross and microscopic evaluation of the repair. Diaphragmatic function was evaluated by inspiratory force against a closed airway and by selective phrenic nerve stimulation (PNS). Serial fluoroscopy was used to evaluate diaphragmatic motion. Grossly the diaphragms in all groups showed compensatory growth. Microscopically the silastic was encapsulated without adherence, while PTFE showed tissue ingrowth. Maximal inspiratory force was equivalent in all groups but selective PNS revealed left-sided impairment in all experimental groups. Fluoroscopy showed paradoxical motion of the diaphragm in the muscle flap group for 1 to 2 months, and in the silastic repair group for 2 to 3 weeks, with near normal motion in the PTFE group for the entire postoperative period. These differences disappeared by 6 months. Prosthetic materials or muscle flaps are all safe for repair of large diaphragmatic hernias. Diaphragmatic growth occurs and the prosthesis remains in place. Physiologic impairment is minimal and not of clinical importance. Use of PTFE may be the preferred method as it develops better tissue incorporation and results in more normal diaphragmatic motion in the critical early postoperative period.

Animals

Abnormal pulmonary function associated with diaphragmatic pleural plaques due to exposure to asbestos.

Pulmonary function was measured in 79 men with diaphragmatic pleural plaques (DPP) as the only abnormality characteristic of asbestos disease on chest radiographs. They were selected from 4572 construction and shipyard workers exposed to asbestos. Abnormalities of pulmonary function in 21 non-smokers and 43 current smokers were compared with referent values adjusted for height, age, and duration of cigarette smoking. In the non-smokers, flows (FEV1) FEF75-85 and FEV1/FVC) were reduced and TGV and RV/TGV were raised. Current smokers had similar significant reductions. Thus by contrast with some current opinion that plaques are "an index only of past asbestos exposure," workers with plaques, even limited to the diaphragm, have functional impairment typical of pulmonary asbestosis. This suggests that they have pulmonary asbestosis, which is below the threshold of radiographic recognition.

Aged