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Biomedical subjects

A C Bryan

Publications and source records attributed to A C Bryan.

At least 19 recordsLinked to original sources

Relationship between PaO2 and lung volume during high frequency oscillatory ventilation.

The relationship between oxygenation and lung volume during high frequency oscillatory ventilation (HFOV) was studied. We ventilated anesthetized, tracheostomized adult rabbits that were rendered surfactant-deficient by lung lavage. Lung volume was measured by the 'disconnection technique'. In the first experiment, HFOV was commenced after conventional mechanical ventilation (CMV) for 1 hr. In the absence of sustained inflation (SI), oxygenation improved with time during HFOV. In the second experiment, HFOV was instituted after CMV for 4 hr. In the absence of SI, all animals expired during the experimental period. In the third experiment we ventilated rabbits for 4 hr and then switched to HFOV. We applied SI first and increased mean airway pressure (MAP) by increments of 2 cmH2O every 15 min. However, there was little improvement in PaO2 despite the use of repeated SI and the increase in MAP. We conclude that oxygenation has a linear relationship to lung volume during HFOV, and that secondary lung injury due to long-term CMV impairs the response to HFOV. Therefore, it is important to minimize the risk of such secondary injuries before instituting HFOV.

Airway Resistance

Pulmonary hypertension after postlavage lung injury in rabbits: possible role of polymorphonuclear leukocytes.

Previous studies showed that repeated lung lavage leads to a severe lung injury with very poor gas exchange, a substantial protein leak into the alveoli with hyaline membrane formation, pulmonary hypertension, and migration of granulocytes (PMN) into the alveolar spaces. Depletion of PMN leads to a better gas exchange and a markedly decreased protein leak with only scanty hyaline membranes. In this study we show that there is sustained pulmonary hypertension after the lung lavage, but in PMN-depleted rabbits there is no postlavage increase in pulmonary arterial pressure. Changing the shunt fraction by manipulating mean airway pressure still leads to a hypoxic vasoconstriction with increase of pulmonary arterial pressure. Thus, after lung lavage, pulmonary reactivity to hypoxia is still preserved. Comparisons between high-frequency ventilation and conventional mechanical ventilation at the same mean airway pressures showed that equal mean airway pressure in these two very different modes of ventilation do not translate into the same mean functional lung volumes.

Animals

Sequential pulmonary function measurements during treatment of infantile chronic interstitial pneumonitis.

Three infants with histologically confirmed chronic interstitial pneumonitis were treated with monthly intravenously administered high doses of methylprednisolone with or without daily hydroxychloroquine therapy. We applied the multiple occlusion technique to measure the static respiratory system compliance, and the end-inspiratory occlusion technique to measure passive respiratory system compliance, resistance, and time constant. When assessed by clinical criteria and pulmonary function measurements, all three patients showed improvement with this treatment. Clinical improvement was associated with an increase in respiratory system compliance as measured by both techniques (60% to 100% increase in all patients). The passive respiratory resistance and the time constant did not closely reflect the clinical course. We conclude (1) that high doses (pulses) of methylprednisolone and daily oral doses of hydroxychloroquine are effective in the treatment of infantile chronic interstitial pneumonitis and (2) that the respiratory system compliance, measured by both pulmonary function techniques, correlates well with the response to treatment and change in clinical status.

Airway Resistance

Lung injury in a surfactant-deficient lung is modified by indomethacin.

Repetitive total lung lavage in adult rabbits leads to a reproducible severe surfactant-deficient lung injury. Hypoxemia requiring mechanical ventilation occurs, accompanied by a substantial pulmonary hypertension, a large intra-alveolar protein leak, peripheral neutropenia, and pathological features of marked neutrophil infiltration with extensive hyaline membrane formation. Pretreatment with indomethacin abolishes postlavage pulmonary hypertension, preserves a slightly better lung function with higher arterial PO2, and prevents the postlavage peripheral neutropenia found in untreated animals. Pretreatment with a thromboxane A2 receptor blocker (L 655,240, Merck Frosst, Canada) also completely attenuated pulmonary hypertension, providing evidence that thromboxane A2 mediates pulmonary arterial hypertension after lung lavage. However, specific thromboxane receptor blockade had no other long-lasting beneficial effects on the ongoing injury in this model.

Animals

A model of the maturation of respiratory control in the newborn infant.

A model of automatic neonatal respiratory control has been constructed as an aid in the investigation of a possible maturation in respiratory control loops during the newborn period. The primary objective was to provide a framework for investigating this hypothesis without the need for external stimuli or invasive measurements. Spontaneous sighs provide a physiological disturbance to the respiratory system by transiently altering the levels of the blood gases. The dynamic ventilatory response following such a disturbance was modeled. A change from a highly damped to less damped pattern was found when model parameter values were varied to mimic maturation in the neonatal period. A perturbation model analysis demonstrated the dynamic ventilatory response is most sensitive to factors affecting the gain of the peripheral chemoreflex loop. It is concluded that the model provides valuable insight into the hypothesis that the peripheral chemoreflex matures during the neonatal period and provides a viable method for testing this in the human infant.

Humans

Comparison of diaphragmatic fatigue in newborn and older rabbits.

The ability to maintain occlusion pressure (i.e., fatigability) during activation of the diaphragm via phrenic nerve stimulation was compared in newborn (less than 14 days old) and older (greater than 30 days old) rabbits. The younger animals had lower maximum inspiratory pressures (MIP) and markedly greater falls in pressure during sustained diaphragmatic contractions at greater than 40% MIP than did the older animals. Histological analysis showed a paucity of high-oxidative type I fibers in the diaphragms of the young animals. We therefore conclude that the newborn rabbit diaphragm is extremely susceptible to fatigue and that this susceptibility correlates with the distribution of muscle fiber types.

Age Factors

Effect of surgical repair on respiratory mechanics in congenital diaphragmatic hernia.

To determine whether surgical repair of congenital diaphragmatic hernia (CHD) results in improvement in respiratory mechanics, we measured respiratory system compliance in nine patients (five survivors and four nonsurvivors) before and after operation. In all nine infants, CHD was diagnosed within 6 hours of life, and surgical repair was through an abdominal approach after a period of stabilization. Measurements were made noninvasively, using the passive expiratory flow-volume technique. In only one of the nine infants did compliance immediately improve after surgical repair, and in another it showed no change. Both of these infants survived, with an uneventful postoperative course. In the remaining seven infants, however, postoperative compliance immediately decreased to 10% to 77% from the preoperative value. The four infants with more than 50% decrease in compliance died with increasing hypoxemia and acidosis. These results suggest that respiratory mechanics in CHD, far from improving, frequently deteriorate as a result of repair of the hernia. The role of urgent surgery in this malformation should be reevaluated.

Hernia, Diaphragmatic

Reduction of platelet counts induced by mechanical ventilation in newborn infants.

The association between platelet counts and mechanical ventilation was assessed in 61 newborn infants with respiratory distress syndrome, 10 infants with congenital diaphragmatic hernia, and 10 infants with tracheoesophageal fistula. A significant decrease in platelet counts was observed during mechanical ventilation: (mean +/- SD) reduction of 39% +/- 5%, 42% +/- 5.6%, and 11.9% +/- 5.4% in the three groups, respectively, independent of other causes. In the group with congenital diaphragmatic hernia, there was a significant correlation between mean airway pressure and the reduction in platelet counts. In a subsequent series of experiments, platelet counts were recorded before and during ventilation in rabbits. A significant mean decrease of 37.3% in platelet counts was associated with ventilation with either air or pure oxygen. Results of these studies indicate that mechanical ventilation itself may cause a major decrease in platelet count in newborn infants.

Animals

Effect of granulocyte depletion in a ventilated surfactant-depleted lung.

In a previous paper Cutz, Bryan et al. showed that in rabbits after repetitive lung lavage high-frequency oscillatory ventilation maintained excellent gas exchange and did not cause hyaline membrane formation (J. Appl. Physiol. 55: 131-138, 1983). In contrast, conventional mechanical ventilation had poor gas exchange and extensive hyaline membrane formation and we attributed these differences to mechanical barotrauma. However, we completely overlooked the large number of granulocytes in the damaged lung. To investigate this using the same model we have used mechanical ventilation on two groups of rabbits, one with normal granulocytes, the other depleted of granulocytes by pretreatment with nitrogen mustard. The nondepleted rabbits had poor gas exchange, a substantial protein leak into the lung and extensive hyaline membranes. The depleted animals had good gas exchange, a very small protein leak and no hyaline membranes. Repletion of granulocytes from donor rabbits lead to poor gas exchange and hyaline membrane formation. It is concluded that lung lavage causes prompt margination of granulocytes which become activated by the ongoing epithelial barotrauma of conventional ventilation.

Animals

Diaphragmatic work of breathing in premature human infants.

Present methods of assessing the work of breathing in human infants do not account for the added load when intercostal muscle activity is lost and rib cage distortion occurs. We have developed a technique for assessing diaphragmatic work in this circumstance utilizing measurements of transdiaphragmatic pressure and abdominal volume displacement. Eleven preterm infants without evidence of lung disease were studied. During periods of minimal rib cage distortion, inspiratory diaphragmatic work averaged 5.9 g X cm X ml-1, increasing to an average of 12.4 g X cm X ml-1 with periods of paradoxical rib cage motion (P less than 0.01). Inspiratory work was strongly correlated with the electrical activity of the diaphragm as measured from its moving time average (P less than 0.05). Assuming a mechanical efficiency of 4% in these infants, the caloric cost of diaphragmatic work may reach 10% of their basal metabolic rate in periods with rib cage distortion. When lung disease is superimposed, the increased metabolic demands of the diaphragm may predispose preterm infants to fatigue and may contribute to a failure to grow.

Diaphragm

Comparison of methods of measurement of compliance of the respiratory system in children.

Compliance of the respiratory system (Crs) was compared using 2 previously described methods, namely, the passive expiratory flow and multiple occlusion techniques. These 2 methods have the advantage of being totally noninvasive, but both have limitations precluding their use in some circumstances. The results of this study of 10 intubated patients, who varied widely in age (premature newborn to adolescence) and diseases, showed no significant difference between the Crs obtained by the 2 methods. The Crs measurements can therefore be used interchangeably, the choice of technique being dependent on the subjects' clinical state.

Child

Tidal volumes required to maintain isocapnia at frequencies from 3 to 30 Hz in the dog.

We ventilated seven mongrel dogs with high frequency oscillatory ventilation (HFO) at frequencies from 3 to 30 Hz. At each frequency, the tidal volume required to achieve isocapnia (VTiso) was measured by plethysmography. In an individual dog, VTiso could be related to frequency by an equation of the form VTiso = KfA. A was similar for the seven dogs, A = -0.54 +/- 0.03. K varied from 179 to 325 cc- Hz-A, reflecting differences between the dogs in dead space, CO2 production and gradient for gas transport. This relation is consistent with that predicted from the data of previous investigators who used different ventilators, circuits and methodology. From 3 to 30 Hz, VTiso decreased from 1.2 to 0.4 times anatomic plus equipment dead space, but minute volumes required to maintain isocapnia increased from 6 to 18 times those required during conventional ventilation. We conclude that low tidal volume ventilation is also high minute volume ventilation.

Animals

Long volume during high frequency oscillation.

Previous investigators have reported alarming gas trapping during high frequency oscillation. We have assessed trapping by measuring the difference between occlusion pressure (alveolar pressure) and measured maximal mean airway circuit pressure. Under normal operating conditions, we were unable to demonstrate trapping in normal or lung-lavaged rabbits at 15 or at 25 Hz, or in infants with infant respiratory distress syndrome, but we could produce trapping by operating at unusually low mean airway pressure. At these low pressures, lung volume is low, and we believe that choke points develop that limit maximal expiratory flow.

Animals

State-related incidence of spontaneous breathing during high frequency ventilation.

Previous reports indicate that apnea is induced by high frequency ventilation (HFV) in anesthetized animals. We have studied conscious dogs ventilated with HFV during sleep and wakefulness to determine if this apnea is state related. Eucapnic apnea or very low breathing frequencies were observed during quiet wakefulness, quiet sleep and tonic REM sleep. However, spontaneous breathing at nearly normal rates was invariably seen during phasic REM sleep. We conclude that HFV as administered induces apnea or near apnea in conscious animals and that the inhibitory pathways causing this apnea are probably disabled during phasic REM sleep.

Animals