Control of breathing in patients with myasthenia gravis.

Control of breathing has seldom been investigated in patients with myasthenia gravis (MG). We evaluated lung volumes and respiratory muscle strength by measuring maximal inspiratory (MIP) and expiratory (MEP) pressures in 12 patients with moderate generalized (IIb) MG before and after an orally administered therapeutic dose (120 mg) of Mestinon, and in 11 age- and sex-matched normal subjects. Breathing pattern, mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (EMGd) and intercostal (EMGint) muscles were evaluated during both room-air breathing and hypercapnic rebreathing. Before Mestinon, patients exhibited a slight decrease in VC, and normal TLC and FEV1/VC ratio. Compared with the normal control group, patients also exhibited respiratory muscle weakness (marked decrease in MIP and MEP; p less than 0.001 for both), and more rapid and shallower breathing (RSB): lower tidal volume (VT), inspiratory time (TI), expiratory time (TE), and greater respiratory frequency (f); mean inspiratory flow (VT/TI) and P0.1 were slightly supernormal, whereas both EMGd and EMGint were significantly higher in patients. During hypercapnic rebreathing, ventilation (VE) (p less than 0.001), VT (p less than 0.001), VT/TI, (p less than 0.003), P0.1 (p less than 0.003), and EMGd (p less than 0.001) response slopes to increasing PCO2 were found to be lower, whereas EMGint response slope was normal. At 60 mm Hg of PCO2 in the two groups the difference in terms of breathing pattern, P0.1, and EMGd were similar to that observed during room-air breathing. After Mestinon, VC (p less than 0.005), MIP (p less than 0.02), and MEP (p less than 0.01) significantly increased, whereas spontaneous breathing remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory mechanisms of exercise intolerance in chronic heart failure.

Mechanisms that have been suggested to underlie the abnormal ventilatory response to exercise in patients with chronic congestive heart failure (CHF) include high pulmonary pressures, ventilation-perfusion mismatching, early metabolic acidosis, and abnormal respiratory control. To evaluate the role that ventilation and gas exchange play in limiting exercise capacity in patients with CHF, data from 33 patients with CHF and 34 normal subjects of similar age who underwent maximal exercise testing were analyzed. Maximal oxygen uptake was higher among normal subjects (31.7 +/- 6 ml/kg/min) than among patients with CHF (17.7 +/- 4 ml/kg/min; p less than 0.001). The ventilatory equivalent for oxygen, expressed as a percentage of maximal oxygen uptake, was 25% to 35% higher among patients with CHF compared with normal subjects throughout exercise (p less than 0.01). A steeper component effect of ventilation on maximal oxygen uptake was observed among normal subjects compared with patients with CHF, which suggests that a significant portion of ventilation in CHF is wasted. Maximal oxygen uptake was inversely related to the ratio of maximal estimated ventilatory dead space to maximal tidal volume (VD/VT) in both groups (r = -0.73, p less than 0.001). Any given oxygen uptake at high levels of exercise among patients with CHF was accompanied by a higher VD/VT, lower tidal volume, and higher respiratory rate compared with normal subjects (p less than 0.01). Relative hyperventilation in patients with CHF started at the beginning of exercise and was observed both below and above the ventilatory threshold, which suggests that the excess ventilation was not directly related to earlier than normal metabolic acidosis. Thus abnormal ventilatory mechanisms contribute to exercise intolerance in CHF, and excess ventilation is associated with both a higher physiologic dead space and an abnormal breathing pattern. The high dead space is most likely due to ventilation-perfusion mismatching in the lungs, which is related to poor cardiac output, and the abnormal breathing pattern appears to be an effort to reduce the elevated work of breathing that is caused by high pulmonary pressures and poor lung compliance.     

Action of the inspiratory muscles of the rib cage during breathing in newborns

To determine whether the rib cage muscles actively contribute to tidal volume change in infancy, we measured tidal volume (VT), using a pneumotachograph, respiratory gastric pressure swings (Pga), using a liquid-filled gastric catheter, and rib cage and abdominal volume, using respiratory inductive plethysmography in 15 newborns, both before and during 2% CO2-induced hyperventilation. Active rib cage expansion produced by phasic contraction of the inspiratory muscles of the rib cage should reduce respiratory abdominal pressure fluctuations by moving the anterior abdominal wall outward and cephalad, thereby having an expanding influence on the abdominal cavity. During quiet sleep (n = 13), CO2-induced hyperventilation was associated with significant increases in VT, Pga, rib cage volume (Vrc), and abdominal volume (Vab). Increments in Pga were small relative to VT, as shown by an increase in the slope of the VT versus Pga respiratory loop (VT/Pga) in all subjects (p less than 0.001, paired t test). CO2 breathing was associated with an increase in the contribution of the rib cage compartment to total volume change (Vrc/Vrc + Vab) in all infants studied (p less than 0.001, paired t test), and the total volume response to hyperventilation was more strongly related to changes in rib cage volume (slope = 0.62, r = 0.90) than to abdominal volume (slope = 0.31, r = 0.60). During REM sleep (n = 6), mean VT/Pga did not change significantly, and the rib cage contribution to tidal breathing decreased in three of six infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypnosis effect on carbon dioxide chemosensitivity

Hypnosis is an induced state of heightened suggestibility during which certain physiologic variables can be altered. To investigate if carbon dioxide (CO2) chemosensitivity could be blunted during this suggestible state, we measured hypercapnic ventilatory response (HCVR, delta VE/delta PaCO2), oxygen consumption (VO2), breathing pattern (VT and f), inspiratory flow rate (VT/Ti), and inspiratory timing (Ti/Ttot) in 20 healthy subjects. Mouth occlusion pressures (P0.1) were measured in the last nine subjects. Resting oxygen consumption and minute ventilation were measured during awake and hypnotic control states. The HCVR was measured spontaneously and with the suggestion to maintain normal ventilation during both awake and hypnotic conditions. It was found that without a change in metabolism, ventilatory responses to CO2 could be blunted both voluntarily, and to a greater degree, with hypnotic suggestion. These findings may have important implications in clinical settings in which patients suffer from marked dyspnea secondary to increased ventilatory chemosensitivity.     

Selective reduction of genioglossal muscle activity by alcohol in normal human subjects

We recorded ventilation and genioglossal electromyographic activity in 12 awake, normal subjects before and after they drank 1 ml of ethyl alcohol per kg of body weight. Measurements were made during quiet room air breathing and during hypercapnic rebreathing. Alcohol did not alter minute ventilation, the pattern of breathing, or the ventilatory response to CO2, but it significantly reduced genioglossal activity in both quiet breathing and hypercapnia. The effect was more consistent in male than in female subjects. These results indicate that the neural mechanisms underlying the respiratory activity of the genioglossus are more susceptible to depression by alcohol than those serving the muscles of the ventilatory pump. This susceptibility may be important in the exacerbation by alcohol of obstructive apnea during sleep.     

Ventilatory and occlusion pressure responses to hypercapnia in patients with chronic renal failure

Little is known of the effect of chronic renal failure (CRF) on ventilatory regulation. In 38 subjects (19 healthy, 19 with CRF before and after dialysis), we performed measurements of ventilation (VE) and occlusion pressure (P0.1) while the subjects were breathing air and hypercapnic gas mixtures. The results have shown that (1) during air ventilation, CRF patients exhibited lower values of VE and P0.1, which returned to normal after dialysis; (2) during hypercapnic ventilation, CRF patients had the same response as healthy subjects for VE but higher P0.1; hemodialysis induced an upward shift of the CO2 response curve in CRF patients. A twofold mechanism is probably involved: pulmonary edema, which reduces lung elasticity, and neuromuscular hypoexcitability, both implying a stronger central command.     

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)     

Evaluation of respiratory inductive plethysmography in the measurement of breathing pattern and PEEP-induced changes in lung volume.

STUDY OBJECTIVE: To assess the accuracy of the respiratory inductive plethysmography in the measurement of PEEP-induced changes in end-expiratory lung volume during mechanical ventilation and its accuracy and stability in the measurement of ventilation during controlled mechanical ventilation and spontaneous breathing. DESIGN: An open comparison between two methods using a criterion standard. Either a pneumotachometer (mechanically ventilated patients) or a spirometer (spontaneously breathing subjects) was used as the reference method. SETTING: Tertiary care center; a multidisciplinary intensive care unit and a metabolic research unit. PATIENTS: Six mechanically ventilated, paralyzed postoperative open heart surgery patients, six spontaneously breathing COPD patients, and eight healthy volunteers. INTERVENTIONS: Stepwise increases and reductions of PEEP from zero to 12 cm H2O during controlled mechanical ventilation; repeated validation of the calibration of the respiratory inductive plethysmography (RIP) in both mechanically ventilated and spontaneously breathing subjects. MEASUREMENTS AND RESULTS: The baseline drift of the RIP in vitro was 10 ml/150 min and in a ventilated model it was 20 ml/150 min. In mechanically ventilated patients, the mean error of the calibration after 150 min was within +/- 5 percent. Change in end-expiratory lung volume (EELV) during the stepwise increase of PEEP up to 12 cm H2O was 849 +/- 136 ml with the RIP and 809 +/- 125 ml with the pneumotachometer (PT), and during the stepwise reduction of PEEP it was 845 +/- 124 ml and 922 +/- 122, respectively (not significant [NS]. The mean difference between methods in the measurement of change in EELV was -6.6 +/- 3.5 percent during increasing and 6.6 +/- 6.7 percent during decreasing PEEP (NS). Both in mechanically ventilated and spontaneously breathing subjects, the difference between methods was significant for VT and VT/TI. The difference in VT was -2.2 +/- 0.2 percent during mechanical ventilation, -1.1 +/- 0.5 percent in spontaneously breathing COPD patients, and 2.9 +/- 0.4 percent in healthy volunteers (NS between groups). CONCLUSIONS: The RIP is sufficiently accurate for the measurement of PEEP-induced changes in EELV during controlled mechanical ventilation. The accuracy of tidal volume measurement is similar during mechanical ventilation and spontaneous breathing. The calibration of the RIP is stable enough for bedside monitoring of changes in lung volumes.     

The effect of hypoxia on posthyperventilation breathing

The breathing patterns after voluntary hyperventilation were determined in 14 healthy young subjects under four different conditions: (1) normoxia, (2) hyperoxia, (3) hypoxia, and (4) sudden administration of oxygen against a background of hypoxia to evaluate the effect of hypoxia on the pattern of the posthyperventilation breathing. Under hypoxia the ventilation in the immediate posthyperventilation period was depressed although no decreased ventilation was observed under hyperoxia or normoxia in this period. Sudden administration of oxygen depressed further the decreased ventilation in the posthyperventilation period.     

Pathogenesis of respiratory insufficiency in myotonic dystrophy: the mechanical factors

We have previously shown that the chemosensitivity of the respiratory centers is well preserved in myotonic dystrophy but that the ventilatory output is reduced. The present study was designed to determine at which degree of ventilatory performance weakness and fatigability of the respiratory muscles are interfering with ventilation and which mechanical factors contribute to the tachypnea of patients with myotonic dystrophy at rest and during low ventilatory output. We studied 10 patients with the disease and 10 normal control subjects. The strength of respiratory muscles was assessed by measurements of maximal pressure-volume diagrams generated against airway occlusion. Performance was evaluated during 1-min maximal voluntary ventilation (1-min MVV) test, during 7-min 7% CO2 breathing and during quiet breathing. Occlusion pressure (P0.1) in patients at rest was slightly higher than in control subjects, and during CO2 breathing, it was similar to that of control subjects. Maximal static pressure was reduced in patients to an average of 35% of that of control subjects. During the 1-min MVV test, there was a 50% reduction in esophageal and transdiaphragmatic pressure output (Pes, Pdi) in patients, resulting in similar reduction in ventilation (VE) and patients had rapid cycles of alternating dominant thoracic and abdominal volume displacements (Vrc/Vabd) suggesting respiratory muscle fatigue. During the 3- to 4-fold increase in breathing drive induced by hypercapnia, pressure output and the Vrc/Vabd were identical in both groups. However, ventilation was reduced in patients who had tachypneic respiration. In patients, tachypnea was also observed during quiet breathing. This tachypnea was associated with higher impedance of the respiratory system (Zrs) in patients and identical impedance of the lung (ZL) in both groups. In addition, Pdi during tidal volume was significantly higher in patients. These data demonstrate that the ventilatory output in out patients was altered predominantly by weakness and fatigability of the respiratory muscles during high ventilatory performance and by increased impedance of the respiratory system at lower degrees of ventilation.     

Arterial to end-tidal CO2 difference in respiratory disease.

The difference in CO2 tension between arterial blood and end-tidal alveolar gas (a-end-tidal)DCO2 was found to correlate fairly well with the VD/VT ratio in 13 healthy subjects and 50 patients with pulmonary diseases (r = 0.74), and to discriminate between healthy subjects and patient groups at least as effectively as did the VD/VT ratio. An increase in breathing frequency from 8 to 32/min, without simultaneous change in alveolar ventilation, was associated with a mean increase in (a-end-tidal) DCO2 of several mmHg in both the healthy subjects and the patient groups. It is concluded that measurement of (a-end-tidal)DCO2 seems to be a clinically useful alternative to measurement of VD/VT ratio for evaluation of the wasted ventilation component, provided that the effect of the breathing frequency on (a-end-tidal) DCO2 is taken into account.     

Effects of a face mask and pneumotachograph on breathing in sleeping infants

The effect of facial attachments on breathing was measured by respiratory induction plethysmography (RIP) during quiet sleep in 32 studies in 18 infants. The addition of a face mask plus pneumotachograph led to an increase in tidal volume (VT) (22.0 +/- 13.5%, p less than 0.01) during 5-min sleep studies when compared to measurements using RIP alone. Applying only the mask rim also led to an increase in VT (14.6 +/- 3.1%, p less than 0.05). A significant increase in VT was noted in 3 of 6 infants studied when a lightweight cardboard ring was in place perinasally. Respiratory frequency fell significantly in the mask/pneumotachograph group (-5.9 +/- 10.0%, p less than 0.05) and with the mask rim (-7.4 +/- 8.8%, p less than 0.01), but there was individual infant variation. Minute ventilation rose significantly (19.1 +/- 16.9%, p less than 0.01) only with the addition of the mask and pneumotachograph. Instrument deadspace can account for some of the increase in VT noted, but in its absence, sensory stimulation of the trigeminal area can augment tidal breathing.     

Breathing pattern and neuromuscular drive during CO2 rebreathing in normal man and in patients with COPD

In 11 normal subjects and in 10 patients with chronic obstructive pulmonary disease we evaluated breathing pattern and mouth occlusion pressure (PO.1), while breathing room air and during reinhalation of a hypercapnic hyperoxic gas mixture. In the breathing pattern we analyzed the time and volume components of the respiratory cycle: tidal volume (VT), inspiratory time (Ti), expiratory time (Te), total time of respiratory cycle (Ttot); mean inspiratory flow (VT/Ti) and Ti/Ttot ratios, respiratory frequency (RF) and instantaneous ventilation (VE). In the normal subjects, increase in VE during rebreathing mainly depended on an increase in both VT and VT/Ti without significant changes in Ti. During CO2 rebreathing the patients exhibited a lesser increase in VE compared to normals, due to a lesser increase in VT. However, expressing VT in percent of resting inspiratory capacity showed that VT attained at the end of rebreathing (VTmax) was similar to that noted in the normal subjects at the same minute of rebreathing. Furthermore, percent increase in VE, VT, VT/Ti and PO.1 between resting value and that at 56 mm Hg (delta %), were significant in both groups with a major increase in the normal subjects for VE and VT/Ti. In comparison, delta % decreases in both Te and Ttot were found to be significant only in the normal subjects. VT/Ti was related to VE in a similar way in the two groups. In contrast, in the normal subjects, Ti/Ttot did not increase with increasing VE. During rebreathing increase in PO.1 was found to be similar in the normal subjects and in patients. However, for a given neuromuscular drive VE and VT/Ti were greater in the normal subjects than in the patients. These data show that in the patients as a whole no significant changes in breath intervals occur during CO2 rebreathing. Furthermore, in patients, in spite of a similar increase in neuromuscular drive, the efficiency by which inspiratory muscle output (PO.1) is converted into VT/Ti was found to be reduced.     

The impact of morbid obesity on oxygen cost of breathing (VO(2RESP)) at rest.

Oxygen consumption dedicated to respiratory work (V O(2RESP)) during quiet breathing is small in normal patients. In the morbidly obese, at high minute ventilations, VO(2RESP) is greater than in normal patients, but VO(2RESP) during quiet breathing in these patients is not known. We postulated that such patients have increased VO(2RESP) at rest which may predispose them to respiratory failure when additional respiratory workloads are imposed. We measured baseline VO(2) in morbidly obese patients immediately prior to gastric bypass surgery and again after intubation, mechanical ventilation, and paralysis, and compared their change in VO(2) to nonobese patients scheduled for elective abdominal surgery. Baseline VO(2) was higher in the obese patients compared with control patients (354.6 versus 221.4 ml/min; p = 0.0001) and the change in VO(2) from spontaneous breathing to mechanical ventilation was significant in the obese patients (354.6 versus 297.2 ml/min; p = 0.0002) but not the control patients (221.4 versus 219.8 ml/min; p = 0.86). We conclude that morbidly obese patients dedicate a disproportionately high percentage of total VO(2) to conduct respiratory work, even during quiet breathing. This relative inefficiency suggests a decreased ventilatory reserve and a predisposition to respiratory failure in the setting of even mild pulmonary or systemic insults.     

Hypoxic and hypercapnic breathlessness in patients with type I diabetes mellitus

STUDY OBJECTIVES: The putative role of the performance of inspiratory muscles and breathing pattern in inducing dyspnea has been recently assessed during hypoxic stimulation in patients with type I diabetes (IDDM). Compared to a hypoxic stimulus, a hypercapnic stimulus, which may differently affect the pattern of breathing, could therefore modulate the coupling between respiratory effort and ventilatory output, which is involved in dyspnea sensation. SUBJECTS: Eight stable patients aged 19 to 48 years old, with IDDM (duration of disease, 36 to 240 months) and no smoking history, cardiopulmonary involvement, or autonomic neuropathy; and an age- and sex-matched control group. MEASUREMENTS: Pulmonary volumes, diffusing capacity of the lung for carbon monoxide, time and volume components (tidal volume [VT] and respiratory frequency), dynamic elastance (Eldyn), and swings in pleural pressure (Pessw) were measured. Maximal inspiratory pleural pressure (Pes) during a maximal sniff maneuver (Pessn), respiratory muscle effort or output (Pessw%Pessn), tension time index (TTI) = TI/total breathing cycle time x Pessw(%Pessn), and swing in Pes during VT as a percentage of Pessn were also evaluated. Dyspnea sensation was assessed by a modified Borg scale. Subjects were studied at baseline and during hypoxic and hypercapnic rebreathing tests. RESULTS: Compared to control subjects, patients exhibited normal routine spirometric function and Pessn, but a higher Eldyn, indicating peripheral airway involvement. In patients, but not in control subjects, Eldyn increased during both chemical stimuli and increased more during hypoxia than during hypercapnia. Also, changes in both VT and Pessw(%Pessn) on changes in PCO(2) were lower, while changes in Pessw(%Pessn)/VT, an index of neuroventilatory dissociation (NVD) of the ventilatory pump, on changes in PCO(2) were greater. Changes in VT and NVD for unit change in arterial oxygen saturation were lower and higher, respectively. Changes in Borg scale per changes in NVD were greater during both stimuli. Furthermore, compared to hypoxic conditions, a greater VT for any level of both minute volume and Pessw(%Pessn), and lower changes in Borg scale on changes in Pessw(%Pessn) and Pessw(%Pessn)/VT were found in hypercapnia. Changes in NVD and Borg scale related to changes in Eldyn with both chemical stimuli. CONCLUSIONS: In IDDM, the greater perception of dyspnea is associated with changes in inspiratory effort being out of proportion to changes in VT. The greater increase in Eldyn and the lower increase in VT may, in part, account for the greater perception of breathlessness during hypoxia.     

Optoelectronic plethysmography in intensive care patients

We used optoelectronic plethysmography to study 11 normal subjects during quiet and deep breathing, six sedated and paralyzed patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving continuous positive pressure ventilation (CPPV) (positive end-expiratory pressure [PEEP] = 10 cm H(2)O, tidal volume [VT] = 300, 600, 900 ml), and seven ALI/ARDS patients receiving pressure support ventilation (PSV) (PEEP 10 cm H(2)O, pressure support = 5, 10, 15, 25 cm H(2)O). The volumes measured using optoelectronic plethysmography were compared with measurements taken using spirometry and pneumotachography. The three methods were highly correlated. The discrepancies found were 1.7 +/- 5.9%, -1.6 +/- 5.4%, and 4.9 +/- 6.4% when comparing optoelectronic plethysmography with spirometry, optoelectronic plethysmography with pneumotachography, and spirometry with pneumotachography, respectively. Accuracy of the compartmentalization procedure (upper thorax, lower thorax, and abdomen) was assessed by calculating compartmental volume changes during isovolume maneuvers. The discrepancy from the ideal zero line was -2.1 +/- 48.3 ml. Abdominal contribution to inspired volume was greater for normal subjects than for PSV patients (63 +/- 11% versus 43 +/- 14%, p < 0.001). It decreased with VT for normal subjects (48.5 +/- 15%, p < 0.05), whereas it increased for CPPV patients (61 +/- 10%, p < 0.05). No significant distribution differences were found between 5 and 25 cm H(2)O PSV. We conclude that optoelectronic plethysmography is a feasible technique able to provide unique data on the distribution of chest wall volume changes in intensive care patients.     

Slow breathing reduces chemoreflex response to hypoxia and hypercapnia, and increases baroreflex sensitivity.

OBJECTIVE: To investigate whether breathing more slowly modifies the sensitivity of the chemoreflex and baroreflex. DESIGN SETTING: University of Pavia, IRCCS Policlinico S. Matteo. PARTICIPANTS: Fifteen healthy individuals. INTERVENTIONS: Progressive isocapnic hypoxia and progressive hyperoxic hypercapnia were measured during spontaneous breathing and during a breathing rate fixed at 6 and 15 breaths per minute (b.p.m.). Main outcome measures: Variations in chemo- and baroreflex sensitivity (by monitoring ventilation, oxygen saturation, end-tidal carbon dioxide, R-R interval and blood pressure) induced by different breathing rates. RESULTS: Breathing at 6 b.p.m. depressed (P < 0.01) both hypoxic and hypercapnic chemoreflex responses, compared with spontaneous or 15 b.p.m. controlled breathing. Hypoxic and hypercapnic responses during spontaneous breathing correlated with baseline spontaneous breathing rate (r = -0.52 and r = +0.51, respectively; P = 0.05). Baroreflex sensitivity was greater (P < 0.05) during slow breathing at baseline and remained greater at end rebreathing. CONCLUSIONS: Slow breathing reduces the chemoreflex response to both hypoxia and hypercapnia. Enhanced baroreflex sensitivity might be one factor inhibiting the chemoreflex during slow breathing. A slowing breathing rate may be of benefit in conditions such as chronic heart failure that are associated with inappropriate chemoreflex activation.     

Fog-induced respiratory responses are attenuated by nedocromil sodium in humans

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.     

Unilateral diaphragmatic dysfunction in blunt chest trauma

This study was undertaken to evaluate unilateral diaphragmatic dysfunction within ten days after blunt chest trauma. Thirty patients with unilateral chest injury, or predominantly one-sided injuries, were investigated in the supine position, under analgesia. Right and left hemidiaphragm displacement (DD) was measured, using digital subtraction radiography, during quiet and forced breathing. The diaphragmatic contribution to breathing was determined by rib cage and abdominal circumference measurement changes. In both breathing modes, DD of the injured side was lower than DD of the uninjured side (p less than 0.01, p less than 0.001). Six patients had complete diaphragmatic motionlessness. The inspired air volume due to diaphragmatic motion (Vab) was reduced when compared to normal subjects and Vab/VT ratio was always found to be less than 0.65. The degree of diaphragmatic dysfunction appeared related to injury location and is most severe in injuries of the lower chest which implies direct diaphragm muscle injury, although other mechanisms may be implicated. Diaphragmatic dysfunction can contribute to respiratory failure in these patients, and should be considered.     

Direct vasodilator effect of hyperventilation-induced hypocarbia in autonomic failure patients

Hyperventilation produces small decreases in blood pressure in normal subjects and larger decreases in patients with autonomic failure. The authors studied the mechanism for this observation by measuring mean arterial pressure (MAP) and arterial blood gas (ABG) changes in eight patients with severe primary autonomic failure after various maneuvers designed to alter PaCO2, PaO2, and pH. Maneuvers included voluntary hyperventilation, breathing a 5% CO2/95% O2 mixture, breathing 12% O2, breathing through a 1 meter tube to increase dead space, breathing 100% O2, and infusion of 120 mEq NaHCO3 over 30 minutes. All maneuvers led to expected changes in ABGs. Voluntary hyperventilation lowered MAP by 23 +/- 4 (p less than 0.01) mmHg but MAP was raised 11 +/- 3 and 7 +/- 1 mmHg by hyperventilation resulting from increasing breathing dead space or from breathing 5% CO2, respectively. Breathing 100% O2 or 12% O2 had no significant effect on MAP, and NaHCO3 infusion raised MAP by 8 +/- 4 (p less than 0.05) mmHg. With all maneuvers, change in MAP correlated with change in PaCO2 (r = 0.72, p less than 0.001) and change in pH (r = -0.57, p less than 0.01) but not with PaO2. Multiple regression analysis showed that only changes in PaCO2 predicted the change in MAP for all maneuvers. The authors conclude that a decrease in PaCO2 causes the observed decreases in MAP with hyperventilation. This most likely represents a direct peripheral vasodilator effect of hypocarbia rather than a reflex or centrally-mediated mechanism since our patient population is characterized by inadequate or absent autonomic cardiovascular reflex responses.