Central fatigue of the rabbit diaphragm

This study evaluates the importance of central fatigue of the diaphragm in rabbits subjected to inspiratory muscle resistive loading (IRL). Ten rabbits were subjected to constant IRL while unanesthetized and breathing supplemental oxygen. During 10–20 minutes of spontaneous breathing against IRL, there were no significant changes in arterial oxygen saturation or in diaphragm contractility, measured by the quasi-static transdiaphragmatic pressure response to a 0.3-sec train of 100 Hz supramaximal phrenic nerve stimuli. After an initial decrease due to application of the load, the minute ventilation decreased further, by an average of 15%, while arterial pCO₂ increased to an average of 59 mmHg (p < 0.05). The normalized diaphragm pressure-time index initially increased from 0.02 to 0.18 during IRL, then decreased an average of 29% (p < 0.05). These results show that severe IRL causes a decrease in the level of diaphragmatic effort over time despite increased chemical drive and despite a preserved ability of the muscle to respond to phrenic nerve stimuli. This adaptation may help to prevent peripheral diaphragm fatigue.     

Transmission fatigue of the rabbit diaphragm

This study evaluates the role of transmission fatigue of the diaphragm in rabbits subjected to inspiratory resistive loading (IRL) sufficiently severe to increase peak tidal airway pressure to about 50% of that elicited by 100 Hz phrenic nerve stimulation. After 58 +/- 14 min of IRL, the transdiaphragmatic pressure (Pdi) responses to phrenic nerve stimulation at 20, 60, and 100 Hz were reduced by approximately one third. In contrast, IRL induced no significant change in the response to direct diaphragm stimulation (in the presence of transient neuromuscular blockade). Although respiratory acidosis occurred during IRL (pH 7.04 +/- 0.04, PCO2 90 +/- 10, PO2 131 +/- 38), it was not sufficient to explain the reduced contractility. In a separate series of experiments, the diaphragm compound action potential elicited by unilateral phrenic nerve stimuli was recorded by implanted diaphragm electrodes and the Pdi elicited by contralateral phrenic nerve stimulation at 100 Hz was measured. Both action potential amplitude and Pdi declined during IRL and both improved after 10 min of recovery. These findings demonstrate that transmission fatigue plays a major role in rabbit diaphragm fatigue induced by spontaneous breathing against inspiratory resistance.     

Effect of fatiguing resistive loads on the level and pattern of respiratory activity in awake goats

The effect of respiratory muscle fatigue on inspiratory muscle electrical activity (EMG), transdiaphragmatic pressure and ventilation during spontaneous breathing was examined in three awake goats. Studies were performed during progressive hypercapnia before and immediately after inspiratory muscle fatigue induced by flow resistive loading (IRL). IRL caused a decrease in the high-low ratio of the diaphragm and intercostal EMG and a decrease in Pdi during electrophrenic stimulation. After IRL, inspiratory time, the breathing duty cycle (inspiratory time/total breath cycle time), peak integrated activity of the diaphragm and external intercostal EMG per breath and per minute were all decreased at any given level of PCO2. Changes in the timing of respiratory motor activity and reduced muscle performance after IRL resulted in a decrease in transdiaphragmatic pressure and ventilation during hypercapnia. In conscious goats studied during spontaneous, chemically stimulated breathing, inspiratory muscle fatigue is associated with reductions in diaphragm and external intercostal muscle electrical activity and reductions in transdiaphragmatic pressure and ventilation.     

Free radical scavengers and diaphragm injury following inspiratory resistive loading.

Three groups of NZW rabbits were studied to examine the role of free radical scavengers in preventing diaphragm injury produced by inspiratory resistive load (IRL): control, IRL, and scavenger groups. An IRL (Pao: 45-55 cm H2O) was applied to the IRL and the scavenger groups on Day 1. Free radical scavengers (polyethylene glycol superoxide dismutase, N-acetylcysteine, and mannitol) were given (intravenously) to the scavenger group both before and after the IRL. All rabbits were killed on Day 3 to collect diaphragms. Point counting H&E-stained diaphragm x-sections indicated that abnormal diaphragm muscle in the IRL group was significantly greater than control (p < 0.01). However, it was significantly lower in the scavenger group than the IRL group (p < 0.05) and it did not differ from control. In vitro diaphragm physiological studies found that the twitch tension (p < 0.05) and maximal tension (p < 0.01) in the IRL group were significantly lower than control. The maximal tensions (p < 0.05) in the scavenger group were lower than control. After the fatigue protocol, diaphragmatic contractility in the scavenger group was similar to control and was better maintained compared with the IRL group. We conclude that free radical scavengers can prevent the development of diaphragm injury as evidenced by histology but the protection of diaphragm function is limited.     

Tracheal occlusion pressure: a simple index to monitor respiratory muscle fatigue during acute respiratory failure in patients with chronic obstructive pulmonary disease

STUDY OBJECTIVE: To assess respiratory muscle fatigue in acute respiratory failure in patients with chronic obstructive pulmonary disease and evaluate its influence on weaning patients from mechanical ventilation. DESIGN AND PATIENTS: We studied the time course of tracheal occlusion pressure (P0.1) and high-to-low ratio of the diaphragmatic electromyogram in 16 patients in acute respiratory failure with chronic obstructive pulmonary disease. METHODS: All patients were intubated and studied during a 15-minute weaning period from ventilation. Minute ventilation (VE), arterial blood gases, P0.1 and high-to-low ratio of the diaphragm were measured every day from the onset to the end of acute failure (before extubation) at 5 and 15 minutes into the weaning period. The diaphragmatic electromyogram was recorded with an esophageal electrode and the high-to-low ratio of the electrical signal analyzed to assess diaphragmatic fatigue. MEASUREMENTS AND MAIN RESULTS: In all patients P0.1 was markedly increased (7.1 +/- 2.4 cm H2O, mean +/- SE) on the first day of acute failure and did not change during weaning. In 11 patients, P0.1 had decreased to 4.7 +/- 1.8 cm H2O (P less than or equal to 0.002) before extubation (which was done after 5 to 9 days). In these patients, the high-to-low ratio of the diaphragm decreased rapidly-during the first minutes of weaning on the first day of acute failure and remained low throughout weaning, whereas before extubation no decrease in high-to-low ratio was seen during weaning. In 5 patients, P0.1 did not change significantly from the onset of acute failure and the high-to-low ratio remained low before extubation. These 5 patients had to be reintubated within 2 to 6 days. In both groups of patients, VE did not change significantly from the first to last day of acute failure (10.3 +/- 3 compared with 10.7 +/- 2.1 min-1), whereas blood gases during room air breathing improved significantly from the first to last day of acute failure, respectively, in each group (arterial oxygen pressure [PaO2], 33.5 +/- 1.5 compared with 44 +/- 9 mm Hg (P less than or equal to 0.05) and PaO2 56 +/- 2.3 compared with 49 +/- 2 mm Hg (P less than 0.005). CONCLUSIONS: Extubation should not be done in patients with respiratory muscle fatigue despite improvement in arterial blood gases and clinical status; and P0.1 provides a valid and simple index to assess the likelihood of respiratory muscle fatigue.     

Domiciliary nocturnal nasal intermittent positive pressure ventilation in COPD: mechanisms underlying changes in arterial blood gas tensions.

The improvement in arterial blood gas tensions following assisted ventilation in chronic obstructive pulmonary disease (COPD) has usually been attributed to the relief of incipient or established respiratory muscle fatigue. The contribution of changes in the load placed upon and the drive to the respiratory muscle pump have not been evaluated. We have investigated the contribution of changes in respiratory muscle strength, the ventilatory response to CO2 and ventilatory function to changes in arterial blood gas tensions in eight patients with severe COPD completing six months domiciliary nasal intermittent positive pressure ventilation. Six patients showed a reduction and two an increase in arterial carbon dioxide tension (PaCO2), median (range) for eight patients, -0.9 kPa (-1.5 to +0.4) (p less than 0.05) and seven showed an improvement in arterial oxygen tension (PaO2), +0.7 kPa (-0.4 to +1.7) (p less than 0.05) during daytime spontaneous breathing. The reduction in PaCO2 was not related to increased inspiratory muscle strength but was correlated with a decrease in gas trapping (Spearman rank correlation coefficient (r(S)) 0.85, p less than 0.05) and in the residual volume (r(s) 0.78, p less than 0.05), suggesting reduced small airway obstruction and, therefore, a reduction in load. The change in PaCO2 also correlated with the increase in ventilation at an end-tidal CO2 of 8 kPa during rebreathing (r(s) -0.76, p less than 0.05) suggesting improved chemosensitivity to CO2. Our data do not support the hypothesis that improvements were due to the relief of muscle fatigue. We suggest that the contribution of changes in load and central drive warrant further investigation.     

Mechanism of rib cage inspiratory muscle recruitment in diaphragmatic paralysis

Paralysis of the diaphragm promotes an increase in the activation of the rib cage inspiratory muscles, and previous studies have suggested that this compensation is primarily due to vagal mechanisms (6). To test this hypothesis, we have assessed the effect of diaphragmatic paralysis on the electrical response of 19 parasternal intercostal muscles in eight anesthetized, vagotomized, spontaneously breathing dogs in the supine posture. Complete diaphragmatic paralysis was induced by section of the C5, C6, and C7 phrenic nerve roots in the neck. With the animals breathing room air, diaphragmatic paralysis resulted in a mean 94% increase in the peak height of integrated parasternal activity (p less than 0.001) associated with a 14 mm Hg decrease in arterial PO2 (p less than 0.05) and an 8 mm Hg increase in arterial PCO2 (p less than 0.001). The augmented parasternal activity was unrelated to the duration of inspiration and persisted when the animals were given a hyperoxic gas mixture. Thus the rib cage inspiratory muscles still compensate for diaphragmatic paralysis in the absence of vagal signals and of hypoxemia. This compensation probably results from the considerably augmented CO2 load placed on the extradiaphragmatic muscles.     

Effects of aminophylline on diaphragmatic fatigue during acute respiratory failure

The effects of aminophylline on diaphragmatic fatigue and recovery in the face of hypoxemia and hypercapnic acidosis were studied in anesthetized, spontaneously breathing, dogs. The phrenic nerves were stimulated supramaximally at 10, 20, 50, and 100 Hz during 2 s with electrodes placed around the fifth roots, and the resulting transdiaphragmatic pressure (Pdi) was measured with balloon catheters. The dogs were occluded before the stimulations at functional residual capacity. The latter was monitored by measuring the end-expiratory transpulmonary pressure, which remained constant throughout the experiment. Diaphragmatic fatigue was produced by resistive loaded breathing. At the end of the runs, which lasted 15 +/- 2 min, all the dogs were severely hypoxemic (30 +/- 5 mmHg), hypercapnic (65 +/- 4 mmHg), and acidotic (7.1 +/- 0.05). During the fatigue runs, phrenic stimulation resulted in a marked decrease in Pdi, which amounted at 20 Hz to 70 +/- 8% and 45 +/- 12% of the control values 5 min after the onset of the fatigue runs and at the end, respectively. After recovery (3 h), Pdi and arterial blood gas determinations returned to control values. Identical fatigue runs were repeated with aminophylline infusion (loading dose, 6 mg/kg in 10 min and maintenance dose, 1 mg/kg/h), leading to a plasmatic concentration of 16.4 +/- 2 mg/l. Aminophylline protected the diaphragm against fatigue, and despite the presence of hypoxemia and hypercapnic acidosis, the Pdi generated for a 20 Hz stimulation of the phrenic nerves at identical times of the preceding run amounting to 100 +/- 15% and 85 +/- 10% of control values, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood flow to the canine diaphragm during hemorrhagic shock

Previous studies have shown impairment of diaphragm function during shock. It is possible that the mechanism for this is decreased diaphragm perfusion, which leads to decreased function because of limitation of oxygen transport. In order to examine the degree to which oxygen transport is limited during shock, we measured the changes in blood flow to and oxygen consumption of the diaphragm during controlled hemorrhage. Blood flow through the left phrenic artery (Qdi) was measured with an electromagnetic flow probe as systemic arterial pressure (Pa) was decreased. The Pa-Qdi relationship was found to be linear with slope of approximately 0.145 ml/torr/min, and extrapolated pressure at zero flow of approximately 40 torr in normal control subjects. Inspiratory loading and infusion of isoproterenol led to a parallel shift in the Pa-Qdi curve such that there was a decrease in the extrapolated pressure at zero flow to 9 to 13 torr. Infusion of dopamine led to a parallel shift of the Pa-Qdi curve such that there was an increase in the extrapolated pressure at zero flow from approximately 34 to approximately 45 torr. In the normal control subjects, there was a decrease in oxygen consumption associated with the decrease in Qdi, but this was not true for either loading or isoproterenol. We conclude that during hypotension, blood flow to the diaphragm decreases. However, the diaphragm retains the ability to increase its blood flow in response to metabolic or pharmacologic stimuli. This is done primarily by a parallel shift in the pressure-flow relationship, which may represent a change in the critical closing pressure of the phrenic vasculature.     

Granulocytosis and increased adhesion molecules after resistive loading of the diaphragm.

Upregulation of endothelial cell adhesion molecules, followed by an influx of granulocytes and macrophages, can contribute to exertion-induced skeletal muscle injury. The purpose of this study was to quantify circulating leukocyte subsets, diaphragm injury and infiltrating leukocyte subsets, and surface expression of vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1 in the diaphragm after inspiratory resistive loading (IRL). Eight New Zealand white rabbits underwent 1.5 h of IRL and seven control rabbits underwent a sham procedure. Blood samples, taken at baseline and 2, 6, 12, 24, 48 and 72 h after the onset of IRL or sham, showed that band cell counts had increased at 6 h post-IRL. Point counting of haematoxylin and eosin-stained cross-sections, sampled at 72 h post-IRL, showed greater injury in diaphragms from IRL rabbits compared with controls. Immunohistochemical processing showed increased expression of ICAM-1 and VCAM-1, and higher granulocyte and macrophage counts in IRL diaphragms than control diaphragms. Macrophages were the predominant inflammatory cells. Increased intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, and infiltration of granulocytes and macrophages may contribute to inspiratory resistive loading-induced diaphragm injury.     

Oxygen delivery-independent effect of blood flow on diaphragm fatigue.

To determine the effect of blood flow on diaphragm fatigue independent of oxygen delivery, the left hemidiaphragm was vascularly isolated in 14 pentobarbital-anesthetized, mechanically ventilated dogs. Fatigue (decline in tension generation) of the left diaphragm was induced by phrenic nerve stimulation at 10 Hz, 12/min, duty cycle of 0.5 for 8 min. Two stimulation periods separated by 30 min of rest were performed in each animal. Diaphragmatic O2 delivery during the two periods was the same. In Group 1 (n = 8), the diaphragm was autoperfused from the femoral artery (high O2-low flow) during the first stimulation period. The tension generated by the diaphragm during this period declined progressively to 47.7% of initial values. In the second period in this group, the diaphragm was pump perfused with arterial blood, diluted with an equal volume of 6% dextran at a flow rate twice that of the first period (low O2-high flow). Tension in this period declined to 76% of initial tension (p less than 0.05 compared with high O2-low flow). In Group 2 (n = 6), stimulation performed while perfusing the diaphragm in the first period with diluted arterial blood at a flow rate twice that recorded during autoperfusion (low O2-high flow) produced a decline in tension to 70% of the initial values. In the second period, the diaphragm was perfused with undiluted arterial blood at a flow rate equal to 50% of that of the first period (high O2-low flow). Tension during this period declined to 56% of initial values (p less than 0.05 compared with low O2-high flow).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of oxygen in patients with sleep apnea

The effects of 6 h of continuous low flow, nasally administered oxygen were compared with the effects of breathing air in 10 men and 2 women with obstructive sleep apnea and daytime hypersomnolence. The overall quality of sleep, sleep fragmentation, the pattern of breathing, nocturnal oxygenation, and the clinical effects on daytime hypersomnolence determined by multiple sleep latency testing were evaluated. We found that in non-REM sleep, breathing 3 L/min of oxygen increased baseline percent arterial oxyhemoglobin saturation and decreased both the rate of sleep-disordered breathing from 69 +/- 36 to 56 +/- 39 (mean +/- SD) (p less than 0.02) episodes per hour and the peak fall in arterial oxyhemoglobin saturation from 11.5 +/- 5.6% to 6.5 +/- 4.0% (p less than 0.001). In addition, oxygen significantly reduced the percentage of central and mixed sleep-disordered breathing events, thus increasing the percentage of obstructive sleep-disordered breathing events. In contrast, during REM sleep, neither the baseline nor the peak fall in oxyhemoglobin saturation during disordered breathing improved; however, there was a significant reduction in hourly sleep-disordered breeathing rate from 70 +/- 17 to 56 +/- 23 (p less than 0.02) episodes. These improvements in oxygenation and pattern of breathing were associated with improved sleep architecture characterized by a decrease in the number of awakenings from sleep and an increased total sleep time from 335 +/- 72 to 369 +/- 68 min (p less than 0.05). Although 7 of 12 patients felt more alert after oxygen therapy, there was no overall improvement in multiple sleep latency test results.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intermittent negative pressure ventilation on respiratory muscle function in patients with severe chronic obstructive pulmonary disease

The reduced respiratory muscle strength and increased work of breathing in patients with severe chronic obstructive pulmonary disease (COPD) may predispose these patients to the development of respiratory muscle fatigue and consequent respiratory failure. To test the hypothesis that these patients may be experiencing chronic respiratory muscle fatigue, we studied the effects of resting the respiratory muscles in a group of patients with severe COPD. Fifteen stable patients with severe COPD were randomized into study and control groups. In 8 study group patients (Group B), breathing was assisted with a negative pressure ventilator 3 to 6 h daily for 3 consecutive days. The remaining 7 patients served as controls (Group A) and did not receive any intervention. Baseline lung function was evaluated by spirometry and arterial blood gas determinations. Respiratory muscle strength and endurance were evaluated by maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and the maximal duration that isocapnic hyperventilation equal to 50 and 70% of the 12-s maximal voluntary ventilation could be sustained (DSV). Baseline DSV was determined as the best effort of several practice trials. All measurements were repeated on the final day of assisted ventilation approximately 2 to 3 h after its discontinuation. After assisted ventilation, the DSV at 50 and 70% of the maximal voluntary ventilation improved significantly (p less than 0.05). Maximal inspiratory pressure and MEP increased to 114% (p less than 0.05) and 112% (p = 0.05) of baseline values, respectively. Mean arterial PCO2 in the hypercapnic subgroup of Group B patients decreased from 60 mm Hg before to 52 mm Hg after assisted ventilation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The pattern of respiratory muscle recruitment during pursed-lip breathing.

Data from the present study indicate a change in the pattern of chest wall muscle recruitment and improved ventilation with pursed-lip breathing (PLB) in COPD. Pursed lip breathing led to increased rib cage and accessory muscle recruitment during inspiration and expiration, increased abdominal muscle recruitment during expiration, decreased duty cycle of the inspiratory muscles and respiratory rate, and improved SaO2. In addition, PLB resulted in no change in pressure across the diaphragm and a less fatiguing breathing pattern of the diaphragm. Changes in chest wall muscle recruitment and respiratory temporal parameters concomitant with the increased SaO2 indicate a mechanism of improving ventilation with PLB while protecting the diaphragm from fatigue in COPD. Alterations in the pattern of respiratory muscle recruitment with PLB may be associated also with the amelioration of dyspnea. Further investigation is necessary to explore the relationship between the pattern of respiratory muscle recruitment during PLB and dyspnea.     

Effects of theophylline on canine diaphragmatic contractility and fatigue.

To distinguish the effects of theophylline on respiratory muscle contractility from alterations in respiratory muscle interaction or blood flow, we examined in vitro contractile properties and fatigue of canine diaphragm in two series of experiments. In the first series, a 40-mg/kg aminophylline infusion was given to dogs, and diaphragm strips were removed for in vitro study when stable tissue fixation of the drug was reached. Compared with control bundles examined before aminophylline infusion, no alterations in twitch tension, tetanic tension, or force-frequency characteristics were observed. Moreover, theophylline-treated strips fatigued faster than control strips, whether subjected to repetitive submaximal or maximal contractions (p less than 0.01). In the second series, diaphragm bundles were equilibrated with high theophylline doses (400 mg/L) in vitro, and inotropic effects compared with the results in the first series. Supratherapeutic theophylline concentrations increased force development at low stimulation frequencies (p less than 0.05 at 10 Hz) and significantly elevated twitch-tetanus ratio (p less than 0.01) but did not protect against development of in vitro muscle fatigue. Poor penetration of theophylline in diaphragm bundles in vitro was excluded, since drug concentrations in the muscle bundle and the muscle bath were virtually equal. We conclude that diaphragmatic tissue concentrations correlate well with therapeutic serum and supratherapeutic bath levels and that only high theophylline concentrations increase canine diaphragmatic contractility in vitro. None of the theophylline concentrations studied could protect diaphragm bundles against the development of low- or high-frequency fatigue in vitro.     

Effects of removing oxygen from patients with chronic obstructive pulmonary disease

To determine the acute physiologic effects of removing oxygen from patients with chronic obstructive pulmonary disease (COPD) who are receiving long-term oxygen therapy, we made serial measurements in 20 patients during and after stopping low-flow oxygen therapy. Removing oxygen caused an increase in pulmonary vascular resistance, requiring 2 to 3 h to reach a new steady state. Removing oxygen therapy increased pulmonary vascular resistance index (PVRI) by 31% during rest (8.14 +/- 0.61 versus 6.23 +/- 0.51 units, p less than 0.001) and by 29% during exercise (8.11 +/- 0.9 versus 6.31 +/- 0.7, p less than 0.001). The increase in PVRI occurred because of an increase in pulmonary arterial pressure without a change in pulmonary capillary wedge pressure or cardiac index. At rest the increase in pulmonary arterial pressure caused by stopping oxygen correlated with the decrease in arterial oxygen saturation (r = 0.70, p less than 0.01). Removing oxygen decreased stroke volume index during rest and exercise. Although removing oxygen increased pulmonary vascular resistance, it did not affect systemic arterial pressure or vascular resistance. Stopping oxygen reduced arterial and mixed venous oxygen tension and oxygen delivery during rest and exercise. In patients who had a normal PaCO2 while breathing room air, removing oxygen therapy increased their oxygen consumption; conversely, in those patients who had an elevated PaCO2 while breathing room air, stopping oxygen therapy reduced oxygen delivery and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

External intercostal muscle activity during acute hypoxia in the kitten

The effects of acute hypoxia on the recruitment of external intercostal muscle activity were determined in 12 kittens, aged 14 to 36 days. The animals were anesthetized with 1.23 +/- 0.23% halothane and bipolar electrodes were placed in the costal and crural diaphragm and in dorsal external intercostal muscles. Acute hypoxia was induced by the animals breathing 13% oxygen; arterial gases were sampled during baseline conditions and at 1 and 5 min after induction of hypoxia. Peak-moving average (PA) and minute electromyogram (EMG) activity (PA x f) were recorded during baseline conditions and at 1 and 5 min after onset of acute hypoxia. At 1 min of acute hypoxia, PA and PA x f of the costal diaphragm, crural diaphragm, and external intercostal muscles were significantly increased above baseline values (P less than 0.01). After 5 min of acute hypoxia, PA of all three muscles remained elevated above baseline values (P less than 0.05) but PA x f returned toward baseline levels. Respiratory frequency remained unchanged during the hypoxic stimulus. These data document that the newborn is capable of increasing inspiratory external intercostal muscle EMG activity during acute hypoxia. We speculate that this phasic recruitment could be of physiologic benefit to the newborn by stabilizing the complaint chest wall and by increasing the contribution of rib cage expansion to tidal breathing.     

High frequency chest wall oscillation in patients with chronic air-flow obstruction

In order to assess high frequency chest wall oscillation (HFCWO) as a way to assist spontaneous breathing in obstructive lung disease, we studied 12 patients with severe and stable COPD. HFCWO at 5 Hz were applied by means of an inflatable vest. In order to avoid any discomfort, oscillations were applied only during the expiratory phase of the spontaneous breathing cycle. We compared gas exchange and pattern of breathing during control and HFCWO periods, each lasting 15 min. Minute ventilation did not change, but the pattern of breathing was markedly altered during HFCWO: breathing frequency decreased (p less than 0.001) from 18 +/- 6/min during control to 14 +/- 5/min, whereas tidal volume increased (p less than 0.01) from 600 +/- 200 ml during control to 860 +/- 400 ml. Secondary to this change in the pattern of breathing, arterial PO2 increased slightly (p less than 0.01) from 54 +/- 7 mm Hg during control to 57 +/- 8 mm Hg during HFCWO, and arterial PCO2 significantly (p less than 0.01) decreased from 46 +/- 6 mm Hg during control to 43 +/- 7 mm Hg during HFCWO. In addition, duty cycle (Ti/Ttot) decreased (p less than 0.001) from 0.37 +/- 0.03 s during control to 0.29 +/- 0.05 s during HFCWO. Such a decrease in duty cycle suggest that inspiratory muscle work was facilitated under HFCWO. In 8 patients, we obtained the tension-time index (TTdi), or the product of duty cycle and Pdi/Pdimax, and found that this index significantly decreased (p less than 0.05) from 0.06 +/- 0.03 during control to 0.04 +/- 0.02 during HFCWO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of amiloride on contractility of rat cardiac muscle exposed to chronic hypercapnia and acute acidosis

Papillary muscle preparations from rats with normal arterial oxygen and carbon dioxide tensions and from rats which had been maintained with normal oxygen tension but with hypercapnia for 28 days (FICO2 = 5%) were subjected to acute hypercapnia with or without amiloride, a competitive inhibitor of the Na+/H+ pump. Acclimatisation to hypercapnia reduced the slope of the line relating log tension against the extracellular pH from 0.96(SEM0.06) to 0.71(0.07) (p less than 0.02). Amiloride increased the slope in unacclimatised muscle to 1.39(0.09), p less than 0.001 and in muscles acclimatised to hypercapnia to 1.03(0.13), p less than 0.05. The slope in acclimatised muscles was significantly less steep than in unacclimatised muscle (p less than 0.05). The sarcolemmal Na+H+ exchanger is important in the protection of rat cardiac muscle against acute respiratory acidosis.     

Changes in ventilatory muscle function with negative pressure ventilation in patients with severe COPD

Patients with severe COPD may be in a state of ventilatory muscle (VM) fatigue. In these patients, rapid and shallow breathing has been hypothesized to be a compensatory mechanism that prevents more severe fatigue from taking place. To test these hypotheses, we studied the effects of VM resting in a group of patients with severe COPD. Eleven clinically stable patients with COPD and chronic hypercapnia were studied. Six of them (group A) had a seven-day period of negative pressure-assisted ventilation (NPV), and five (group B) with similar functional characteristics served as a control group. Compared with a normal age-matched control group, both A and B groups exhibited significantly lower tidal volume (VT), inspiratory time (TI), total time of the respiratory cycle (Ttot) and Ti/Ttot ratio, decrease in muscle strength, and greater electromyographic activity of diaphragm (EMGd) and parasternal muscles, but similar ventilation and VT/TI. After the study period, group A exhibited significant increase in VT, Ti, and TI/Ttot (p less than 0.05), and decrease in PaCO2 (p less than 0.05), EMGd, and EMGint (p less than 0.05 for both), and a slight but significant increase in maximal inspiratory pressure (MIP) (p less than 0.05). These data suggest that NPV rests VM, increases their strength, and reduces hypercapnia in patients with severe COPD.