Respiratory changes associated with rapid eye movements in normo- and hypercapnia during sleep

Rapid eye movements during rapid-eye-movement (REM) sleep are associated with rapid, shallow breathing. We wanted to know whether this effect persisted during increased respiratory drive by CO2. In eight healthy subjects, we recorded electroencephalographic, electrooculographic, and electromyographic signals, ventilation, and end-tidal PCO2 during the night. Inspiratory PCO2 was changed to increase end-tidal PCO2 by 3 and 6 Torr. During normocapnia, rapid eye movements were associated with a decrease in total breath time by -0.71 +/- 0.19 (SE) s (P < 0.05) because of shortened expiratory time (-0.52 +/- 0.08 s, P < 0.001) and with a reduced tidal volume (-89 +/- 27 ml, P < 0.05) because of decreased rib cage contribution (-75 +/- 18 ml, P < 0.05). Abdominal (-11 +/- 16 ml, P = 0.52) and minute ventilation (-0.09 +/- 0.21 ml/min, P = 0.66) did not change. In hypercapnia, however, rapid eye movements were associated with a further shortening of total breath time. Abdominal breathing was also inhibited (-79 +/- 23 ml, P < 0.05), leading to a stronger inhibition of tidal volume and minute ventilation (-1.84 +/- 0.54 l/min, P < 0.05). We conclude that REM-associated respiratory changes are even more pronounced during hypercapnia because of additional inhibition of abdominal breathing. This may contribute to the reduction of the hypercapnic ventilatory response during REM sleep.     

Sperm cytology in azoospermia

BACKGROUND: To progress the clinical treatment of neonates, especially in the management of respiration, we have to be able to measure their pulmonary function appropriately. Various methods have been developed, but little is known about the pulmonary function of very low birthweight infants (VLBWI) because of the difficulty in taking their measurements with existing equipment. We have developed a very low dead space pneumotachograph to measure lung function in VLBWI. METHODS AND RESULTS: We used our pneumotachograph on 30 infants each weighing less than 1500 g at birth. The infants were intubated with endotracheal tubes of 2.5 or 2.0 mm diameter to measure tidal volume and minute ventilation in the prone and supine position. The tidal volume in the supine position was 6.99 +/- 0.42 mL/kg and 7.58 +/- 0.38 mL/kg in the prone position (mean +/- SE). The tidal volume was significantly larger in the prone than the supine position (P < 0.05). However, no significant difference was observed in minute ventilation and respiratory rates. CONCLUSION: The tidal volume significantly increased in the prone position in VBLWI, confirming the previous observation of larger healthy infants is also applicable to the very low birthweight infants.     

Suicidal behavior in bipolar and unipolar affective disorders: a meta-analysis

Manual ventilation (MAV) or handbagging is a frequent and often life-saving procedure for neonates; however, few studies allow for an objective evaluation of techniques or possible risks. We compared parameters of ventilation and pulmonary mechanics obtained during routine pressure-limited MAV to those obtained during spontaneous breathing (SPB) in the same infant at approximately the same time. We selected 20 preterm neonates in the recovery phase of respiratory distress syndrome who received periodic MAV and were capable of optimum spontaneous minute ventilation (> 300 mL/kg/min). During MAV compared to SPB we measured higher tidal volume (8.1 +/- 0.5 SE vs. 5.4 +/- 0.4 SE mL/kg, P < 0.001), lower total pulmonary compliance (0.65 +/- 0.05 vs. 1.16 +/- 0.11 SE mL/cmH2O, P < 0.001), end-inspiratory compliance, higher pulmonary resistance (121 +/- 11 vs. 61 +/- 7 SE cmH2O/L/s, P < 0.001) and higher peak inspiratory airflow (2.8 +/- 0.2 vs. 1.6 +/- 0.1 L/s, P < 0.001). Inspiratory time (Ti) was consistently longer during MAV (0.49 +/- 0.02 vs. 0.36 +/- 0.02 SE, P < 0.001) such that during MAV the difference between actual Ti and minimal effective Ti (fivefold inspiratory time constant) was larger (0.29 +/- 0.03 vs. 0.13 +/- 0.03 s, P < 0.05). Our study suggests that operator-dependent ventilatory variables such as tidal volume, inspiratory time, frequency, and airflow need to be further evaluated in order to develop standardized guidelines for the safe administration of MAV. Until then the ventilator used for brief or augmented ventilatory support is a reasonable alternative to administering MAV by inconsistent standards.     

Dual effect of aminophylline on the ventilatory response to hypoxia in the rat

Male Hooded Wistar rats were exposed to three five-minute periods of hypoxia in which they breathed a gas mixture comprising 7% O2 and 93% N2. Before the second and third hypoxic exposures rats were injected (i.m.) with aminophylline (an adenosine antagonist) at a dose of 15 mg.kg-1. In control animals, hypoxia caused an increase in ventilation which was greater during the first than during the fifth minute of hypoxia. Each injection of aminophylline significantly increased ventilation in air-breathing rats. However, the first dose of the drug did not significantly alter the hypoxic ventilatory response. The second dose of aminophylline had two effects on ventilation during hypoxia. It reduced the ventilatory response during the first minute of hypoxia, and also prevented the fall in ventilation between the first and fifth minute of exposure. Ethylenediamine injections had no effect on ventilation or the responses to hypoxia. The results suggest that adenosine has a dual role in respiratory control during hypoxia, one excitatory and the other inhibitory. Although previous studies have already identified such roles for adenosine, the present study may represent the first time in which these have been demonstrated in a single animal model.     

Respiratory effects of desflurane anesthesia on spontaneous ventilation in infants and children

Volatile anesthetics depress spontaneous ventilation in a dose-dependent manner with variations in effects among different drugs. The goal of this prospective study was to assess respiratory changes during spontaneous ventilation using desflurane/O2/N2O anesthesia in two groups of children. Both groups were undergoing minor surgery and consisted of children < 2 yr old (Group I) and children > 2 yr old (Group II). They were examined at 0.5, 1, and 1.5 minimum alveolar anesthetic concentration desflurane anesthesia. Induction of anesthesia was performed via a face mask and a mixture of O2/N2O (40:60) with halothane. At lease 20 min after stopping halothane, the respiratory variables were recorded on desflurane anesthesia. Tidal volume and minute ventilation decreased significantly (P <0.05) as desflurane increased from 0.5 to 1.5 MAC in both groups. At 1.5 MAC, the respiratory rate was greater in Group II than in Group I (P <0.05). In both groups, the increase in end-tidal CO2 was significant at 1.5 MAC versus 1 and 0.5 MAC (P <0.05). Apnea, i.e., no respiratory movement for 20 s, occurred at 1.5 MAC in one patient in each group. The respiratory duty cycle did not change in any of the groups. Both indices of paradoxical respiration--amplitude index and delay index--did not change. IMPLICATIONS: Desflurane induces respiratory depression at concentrations higher than 1 minimum alveolar anesthetic concentration mainly due to a decrease in tidal volume. Therefore, desflurane at high concentrations should be used cautiously in infants and children with spontaneous ventilation.     

Functional magnetic stimulation of the respiratory muscles in dogs

This study assessed the ability of functional magnetic stimulation (FMS) to activate the respiratory muscles in dogs. With the animal supine, FMS of the phrenic nerves using a high-speed magnetic stimulator was performed by placing a round magnetic coil (MC) at the carotid triangle. Following hyperventilation-induced apnea, changes in volume (deltaV) and airway pressure (deltaP) against an occluded airway were determined. FMS of the phrenic nerves produced substantial inspired function (deltaV = 373 +/- 20.5 mL and deltaP = -20 +/- 2.0 cm H2O). After bilateral phrenectomies, maximal inspired deltaV (219 +/- 12.2 mL) and deltaP (-10 +/- 1.0 cm H2O) were produced when the MC was placed near the C6-C7 spinous processes, while maximal expired deltaV (-199 +/- 22.5 mL) and deltaP (11 +/- 2.3 cm H2O) were produced following stimulation near the T9-T10 spinous processes. We conclude: (1) FMS of either the phrenic or upper intercostal nerves results in inspired volume production; (2) FMS of the lower intercostal nerves generates expired volume production; and (3) FMS of the respiratory muscles may be a useful noninvasive tool for artificial ventilation and assisted cough in patients with spinal cord injuries or other neurological disorders.     

Response of upper airway and chest wall muscles to selective brain stem hypoxia in the newborn

In animals with intact peripheral chemosensory afferents, hypoxia differentially affects upper airway (UA) and chest wall muscles. To determine the contribution of brain stem (BS) hypoxia to the response of UA and chest wall muscles during early life, we perfused the BS through a vertebral artery intermittently with blood from an extracorporeal circuit in nine newborn piglets (age 1-5 days). BS perfusions were performed with hypoxemic blood (arterial PO2 32 +/- 6 to 38 +/- 8 Torr) with different levels of BS PCO2 (28 +/- 2, 37 +/- 4, and 56 +/- 5 Torr) while systemic normocapnic hyperoxia was maintained (arterial PCO2 36 +/- 3 to 40 +/- 6 Torr, arterial PO2 345 +/- 73 to 392 +/- 37 Torr). Electromyograms (EMGs) of alae nasi (AN), external intercostal (EI), and diaphragm (DIA) were recorded. Normocapnic hypoxia of the BS induced a sustained increase in AN EMG (P < 0.01, analysis of variance) and depression of EI and DIA EMGs without a transient increase. These contrasting responses were also observed during hypocapnic and hypercapnic hypoxia of the BS and were not affected by inputs from the peripheral chemoreceptors or rostral cerebral structures that were not exposed to hypoxia. We conclude that, despite eliciting the known central respiratory depression, BS hypoxia causes an increase in the respiratory drive to an UA airway muscle. Thus, BS hypoxia elicits a selective rather than a generalized respiratory muscle depression. The respiratory muscles with high energy expenditure (DIA and EI) are depressed while UA muscles are stimulated or disinhibited. This response is independent of the level of BS arterial PCO2.     

Diaphragm activation with intramuscular stimulation in dogs

We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing.     

What makes alcohol-dependent individuals early in abstinence crave for alcohol: exposure to the drink, images of drinking, or remembrance of drinks past?

It has been reported that injection of somatostatin into the brain-stem will lead to apnoea in animals. The aim of this study was to determine whether peripheral administration of octreotide, an analogue of somatostatin, could influence the control of breathing. We measured the tidal volume, respiratory rate and ventilatory response to CO2, before and after the intravenous injection of two dose levels of octreotide (0.1 mg and 0.5 mg) or saline in four conscious adult dogs. Injection of octreotide altered the breathing pattern with a mean decrease in the respiratory frequency of 23% (p<0.05) and an increase in the tidal volume by 16% (p<0.05), resulting in no net change in ventilation. The normal value of the ventilatory response to CO2 ranged between 1.0-3.2 L x min(-1) x mmHg(-1), with a minor variance within each dog but a significant difference amongst the four dogs (p<0.05). No significant change in the ventilatory response to CO2 was observed after octreotide. We conclude that intravenous octreotide alters the pattern of breathing but preserves minute ventilation; peripheral administration of octreotide does not influence the ventilatory response to CO2.     

Physiological dead space/tidal volume ratio during face mask, laryngeal mask, and cuffed oropharyngeal airway spontaneous ventilation

OBJECTIVE: To compare the physiological dead space/tidal volume ratio and arterial to end-tidal carbon dioxide tension (ETCO2) difference during spontaneous ventilation through a face mask, a laryngeal mask (LMA), or a cuffed oropharyngeal airway. DESIGN: Prospective, randomized, cross-over study. SETTING: Inpatient anesthesia at a university department of orthopedic surgery. PATIENTS: 20 ASA physical status I and II patients, without respiratory disease, who underwent ankle and foot surgery. INTERVENTIONS: After a peripheral nerve block was performed, propofol anesthesia was induced and then maintained with a continuous intravenous (i.v.) infusion (4 to 6 mg/kg/h). A face mask, a cuffed oropharyngeal airway, or an LMA were placed in each patient in a random sequence. After 15 minutes of spontaneous breathing through each of the airways, ventilatory variables, as well as arterial, end-tidal, and mixed expired CO2 partial pressure, were measured, and physiological dead space/tidal volume ratio was calculated. MEASUREMENTS AND MAIN RESULTS: Expired minute volume and respiratory rate (RR) were lower with LMA (5.6 +/- 1.2 L/min and 18 +/- 3 breaths/min) and the cuffed oropharyngeal airway (5.7 +/- 1 L/min and 18 +/- 3 breaths/min) than the face mask (7.1 +/- 0.9 L/min and 21 +/- 3 breaths/min) (p = 0.0002 and p = 0.013, respectively). Physiological dead space/tidal volume ratio and arterial to end tidal CO2 tension difference were similar with the cuffed oropharyngeal airway (3 +/- 0.4 mmHg and 4.4 +/- 1.4 mmHg) and LMA (3 +/- 0.6 mmHg and 3.7 +/- 1 mmHg) and lower than with the face mask (4 +/- 0.5 mmHg and 6.7 +/- 2 mmHg) (p = 0.0001 and p = 0.001, respectively). CONCLUSION: Because of the increased dead space/tidal volume ratio, breathing through a face mask required higher RR and expired minute volume than either the cuffed oropharyngeal airway or LMA, which, in contrast, showed similar effects on the quality of ventilation in spontaneously breathing anesthetized patients.     

Respiratory sinus arrhythmia. A phenomenon improving pulmonary gas exchange and circulatory efficiency

BACKGROUND: The primary mechanisms of respiratory sinus arrhythmia (RSA) are understood to be the modulation of cardiac vagal efferent activity by the central respiratory drive and the lung inflation reflex, and the degree of RSA increases with cardiac vagal activity. However, it is unclear whether RSA serves an active physiological role or merely reflects a passive cardiovascular response to respiratory input. We hypothesized that RSA benefits pulmonary gas exchange by matching perfusion to ventilation within each respiratory cycle. METHODS AND RESULTS: In seven anesthetized dogs, a model stimulating RSA was made. After elimination of endogenous autonomic activities, respiration-linked heartbeat fluctuations were generated by electrical stimulation of the right cervical vagus during negative pressure ventilation produced by phrenic nerve stimulation (diaphragm pacing). The vagal stimulation was performed in three conditions; phasic stimulation during expiration (artificial RSA) and during inspiration (inverse RSA) and constant stimulation (control) causing the same number of heartbeats per minute as the phasic stimulations. Although tidal volume, cardiac output, and arterial blood pressure were unchanged, artificial RSA decreased the ratio of physiological dead space to tidal volume (VD/VT) and the fraction of intrapulmonary shunt (Qap/Qt) by 10% and 51%, respectively, and increased O2 consumption by 4% compared with control. Conversely, reverse RSA increased VD/VT and Qap/Qt by 14% and 64%, respectively, and decreased O2 consumption by 14%. CONCLUSIONS: These results support our hypothesis that RSA benefits the pulmonary gas exchange and may improve the energy efficiency of pulmonary circulation by "saving heartbeats."     

Assessment of the respiratory compliance in awake subjects using pressure support

Pressure support (PS), a new mode of ventilatory assistance, is known to induce respiratory muscle relaxation. It was used to obtain reliable measurements of the compliance of the respiratory system (Crs) in awake subjects. PS was applied, through a mouthpiece, at four successive levels (0, 0.75, 1 and 1.25 kPa) to 30 healthy subjects. At the highest PS level, the subject's relaxation was obtained as assessed by a decrease in the occlusion pressure from 0.10 +/- 0.06 to 0.05 +/- 0.04 kPa, whereas the minute ventilation increased (from 7.5 +/- 1.5 to 13.8 +/- 3.3 l.min-1), and the end-tidal carbon dioxide tension (PCO2) decreased (from 5.0 +/- 0.4 to 3.2 +/- 0.5 kPa) below its apnoea threshold. In three subjects, respiratory muscle relaxation was confirmed by a fall in diaphragmatic electromyographic activity. Crs was calculated as the ratio of the tidal volume to the corresponding end-inspiratory airway pressure (i.e. PS level) since, at end inspiration, a zero-flow period was obtained. Crs was highly correlated (r = 0.77) to the height (Ht) of the subjects: Crs (l.kPa-1) = 3.56 x Ht (m) -4.86 (+/- 0.23), allowing normal values to be determined. In order to evaluate the applicability of the method to patients, Crs was measured in four patients with scoliosis, and was found to range from 45-82% of the predicted values. It is suggested that this simple method of Crs determination may be used to characterize various chest wall or pulmonary diseases.     

Effect of acute hypoxia on metabolism and ventilation in awake piglets

We studied the effect of acute sustained hypoxia on ventilation (VE) and oxygen consumption (VO2) over one hour during quiet wakefulness in young (6 days) and older (6 weeks) piglets in thermoneutral conditions during baseline, moderate hypoxia (PaO2 approximately 45 mmHg), and severe hypoxia (PaO2 approximately 30 mmHg). During severe hypoxia, ventilation and pH increased while PaCO2 decreased in both age groups. Blood gas changes (decreases PACO2, increases pH), but not ventilatory changes, were greater in the older piglets (P < 0.05). VO2 decreased similarly (-30%) while VE/VO2 rose over 160% in both age groups. During moderate hypoxia, changes in blood gas, VE, and VO2 were in a similar direction, but smaller in magnitude. We conclude that: (1) changes in blood gases and VO2 are amplified by maturation and severity of hypoxia and (2) blood gas changes are greater in older vs young piglets despite similar ventilatory responses suggesting maturational differences in CO2 production or dead space ventilation.     

Effect of a subanesthetic minimum alveolar concentration of isoflurane on two tests of the hypoxic ventilatory response

BACKGROUND: These experiments were designed to study the effect of 0.1 minimum alveolar concentration isoflurane on the hypoxic ventilatory response as measured by two common methods of hypoxic testing: when normocapnic hypoxia was induced abruptly and when it was induced gradually. We hypothesized that any disparity in results would be due to an isoflurane effect that was manifested differently in the two tests. METHODS: After 20 min for uptake and equilibration of 0.1 minimum alveolar concentration end-tidal isoflurane or carrier gas in hyperoxia, isocapnic hypoxia was induced either abruptly over 60-80 s ("step" test) or gradually over 10 min ("ramp" test), followed by 20 min of isocapnic hypoxia at 45 mmHg end-tidal oxygen. Control of the hypoxic and isocapnic stimuli was accomplished accurately by a computer-controlled dynamic end-tidal forcing system. Eight subjects performed each test in the presence and absence of isoflurane. RESULTS: For both step tests and ramp tests, 0.1 minimum alveolar concentration isoflurane had no effect on minute ventilation during the defined periods of hypoxia. With isoflurane, delta VE45, the acute change in ventilation from hyperoxia to hypoxia, was 97 +/- 20% (mean +/- SEM) of the control response for step tests and 100 +/- 25% of the control response for ramp tests. The step tests produced significantly larger acute hypoxic responses than did the ramp tests, but by the end of 20 min of hypoxia, ventilation was similar for both tests. CONCLUSIONS: Neither method of hypoxic testing demonstrated the level of isoflurane effect reported by others. A comparison of the two methods of hypoxic testing suggests that ramp tests, as commonly performed, do not allow adequate time for full expression of the acute hypoxic ventilatory response. Step tests also better separated the opposing hypoxic effects of carotid body stimulation and central ventilatory depression.     

Respiratory muscle work compromises leg blood flow during maximal exercise

We hypothesized that during exercise at maximal O2 consumption (VO2max), high demand for respiratory muscle blood flow (Q) would elicit locomotor muscle vasoconstriction and compromise limb Q. Seven male cyclists (VO2max 64 +/- 6 ml.kg-1.min-1) each completed 14 exercise bouts of 2.5-min duration at VO2max on a cycle ergometer during two testing sessions. Inspiratory muscle work was either 1) reduced via a proportional-assist ventilator, 2) increased via graded resistive loads, or 3) was not manipulated (control). Arterial (brachial) and venous (femoral) blood samples, arterial blood pressure, leg Q (Qlegs; thermodilution), esophageal pressure, and O2 consumption (VO2) were measured. Within each subject and across all subjects, at constant maximal work rate, significant correlations existed (r = 0.74-0.90; P < 0.05) between work of breathing (Wb) and Qlegs (inverse), leg vascular resistance (LVR), and leg VO2 (VO2legs; inverse), and between LVR and norepinephrine spillover. Mean arterial pressure did not change with changes in Wb nor did tidal volume or minute ventilation. For a +/-50% change from control in Wb, Qlegs changed 2 l/min or 11% of control, LVR changed 13% of control, and O2 extraction did not change; thus VO2legs changed 0.4 l/min or 10% of control. Total VO2max was unchanged with loading but fell 9.3% with unloading; thus VO2legs as a percentage of total VO2max was 81% in control, increased to 89% with respiratory muscle unloading, and decreased to 71% with respiratory muscle loading. We conclude that Wb normally incurred during maximal exercise causes vasoconstriction in locomotor muscles and compromises locomotor muscle perfusion and VO2.     

Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease

OBJECTIVE: To study in anemic patients with chronic obstructive pulmonary disease (COPD) whether blood transfusion reduces minute ventilation and work of breathing (WOB). DESIGN: We prospectively evaluated the minute ventilation and WOB in 20 anemic adults (hemoglobin of <11 g/dL). Ten patients had severe COPD and ten patients were without lung disease. Measurements were made before and after receiving red blood cell transfusion; post-transfusion measurements were made 24 to 36 hrs after the last transfusion. SETTING: The study was performed in the intensive care unit of a tertiary referral center for home mechanical ventilation and for patients considered difficult to wean from mechanical ventilation. PATIENTS: Twenty clinically stable patients (12 female, eight male) with chronic anemia were studied. Ten patients with COPD (mean forced expiratory volume in 1 sec: 0.55+/-0.1 [SD] L) were compared with ten patients without lung disease. All participants had adequate renal and left ventricular function. INTERVENTIONS: Patients received 1 unit of packed red blood cells for each g/dL that their hemoglobin value was less than an arbitrarily defined target value of 11.0 to 12.0 g/dL. Each unit was transfused over 2 hrs and < or =3 units in total was given. MEASUREMENTS AND MAIN RESULTS: Esophageal pressure was measured from a catheter which was positioned in the middle of the esophagus. Flow was measured using a pneumotachygraph connected to a mouthpiece while a nose clip closed the nostrils during the measurements. From these data, respiratory rate, minute ventilation, and inspiratory resistive WOB were computed. Arterial blood gas values, oxygen saturation, hemoglobin, and hematocrit were also measured, and oxygen content was calculated before and 24 to 36 hrs after transfusion. In patients with COPD, hemoglobin increased from 9.8+/-0.8 to 12.3+/-1.1 g/dL due to a mean transfusion of 2.2+/-0.4 (SD) units of red blood cells. There was a reduction in the mean minute ventilation from 9.9+/-1.0 to 8.2+/-1.2 L/min (p < .0001); correspondingly, WOB decreased from 1.03+/-0.24 to 0.85+/-0.21 WOB/L (p< .0001). The capillary P(CO2) increased from 38.1+/-6.0 to 40.7+/-6.8 torr (5.1+/-0.8 to 5.8+/-0.9 kPa) (p < .05). Similarly, capillary P(O2) changed from 56.9+/-8.9 to 52.8+/-7.0 torr (7.6+/-1.2 to 7.0+/-0.9 kPa) (p < .05). In anemic patients without lung disease, minute ventilation, WOB, and the capillary blood gas values did not change after increase of the hemoglobin by a similar degree. CONCLUSIONS: We conclude that red blood cell transfusion in anemic patients with COPD leads to a significant reduction of both the minute ventilation and the WOB. In these patients, transfusion may be associated with unloading of the respiratory muscles, but it may also result in mild hypoventilation.     

One-sample pregnancy diagnosis in elk using fecal steroid metabolites

In utero hypoxia may affect the development of the brain and result in altered respiratory responses postnatally. Using a barometric plethysmograph, we examined the effects of exposing pregnant guinea pigs to 200 ppm carbon monoxide (CO) for 10 h/d from d 23-25 of gestation until term (approximately 68 d) on the ventilatory responses of their 4-5-d-old neonates at rest, and during progressive asphyxia and steady state hypercapnia. Exposure to this concentration of CO produced significantly higher levels of carboxyhemoglobin (COHb) in maternal (8.53 +/- 0.6% versus 0.25 +/- 0.1%) and fetal blood (13.0 +/- 0.4% versus 1.6 +/- 0.1%) from CO-treated animals when compared with controls. Hematocrit was significantly higher in the CO-treated neonates (46.3 +/- 1.0% versus 41.3 +/- 0.9%) at 5-6 d of age, although no difference existed between the groups for COHb at this time. There was no difference between the groups for length of gestation, litter size, or birth weight, but CO-treated neonates were significantly smaller at 4 d of age (102.4 +/- 3.7 g) compared with controls (132.0 +/- 5.0 g). At 4-5 d of age there was no difference between the groups for either tidal volume (VT), respiratory frequency (f), or minute ventilation (VE) at rest, but during steady state hypercapnia (4 and 6% CO2) the CO-treated neonates had a significantly greater VT and VE (but not f) than did controls. During progressive asphyxia, CO-treated animals had a significantly greater VT than did controls from 1-8% CO2. There was a significant fall in f at 1 and 3% CO2 in CO-treated animals; however, this effect did not persist, resulting in a significantly increased VE from 3 to 8% CO2. The inspiratory flow rate (VT/expiratory time) was significantly increased in the CO-treated neonates during progressive asphyxia; this occurred in the absence of a difference in inspiratory time between the groups. These results indicate that prenatal exposure to CO increases CO2 sensitivity in 4-5-d-old guinea pigs. This may be due to developmental alterations in the areas of the brainstem responsible for respiratory control.     

Comparative physiologic effects of noninvasive assist-control and pressure support ventilation in acute hypercapnic respiratory failure

STUDY OBJECTIVE: To compare the effects of noninvasive assist-control ventilation (ACV) and pressure support ventilation (PSV) by nasal mask on respiratory physiologic parameters and comfort in acute hypercapnic respiratory failure (AHRF). DESIGN: A prospective randomized study. SETTING: A medical ICU. PATIENTS AND INTERVENTIONS: Fifteen patients with COPD and AHRF were consecutively and randomly assigned to two noninvasive ventilation (NIV) sequences with ACV and PSV mode, spontaneous breathing (SB) via nasal mask being used as control. ACV and PSV settings were always subsequently adjusted according to patient's tolerance and air leaks. Fraction of inspired oxygen did not change between the sequences. MEASUREMENTS AND RESULTS: ACV and PSV mode strongly decreased the inspiratory effort in comparison with SB. The total inspiratory work of breathing (WOBinsp) expressed as WOBinsp/tidal volume (VT) and WOBinsp/respiratory rate (RR), the pressure time product (PTP), and esophageal pressure variations (deltaPes) were the most discriminant parameters (p<0.001). ACV most reduced WOBinsp/VT (p<0.05), deltaPes (p<0.05), and PTP (0.01) compared with PSV mode. The surface diaphragmatic electromyogram activity was also decreased >32% as compared with control values (p<0.01), with no difference between the two modes. Simultaneously, NIV significantly improved breathing pattern (p<0.01) with no difference between ACV and PSV for VT, RR, minute ventilation, and total cycle duration. As compared to SB, respiratory acidosis was similarly improved by both modes. The respiratory comfort assessed by visual analog scale was less with ACV (57.23+/-30.12 mm) than with SB (75.15+/-18.25 mm) (p<0.05) and PSV mode (81.62+/-25.2 mm) (p<0.01) in our patients. CONCLUSIONS: During NIV for AHRF using settings adapted to patient's clinical tolerance and mask air leaks, both ACV and PSV mode provide respiratory muscle rest and similarly improve breathing pattern and gas exchange. However, these physiologic effects are achieved with a lower inspiratory workload but at the expense of a higher respiratory discomfort with ACV than with PSV mode.     

Theophylline improves measurements of respiratory muscle efficiency

To determine the effect of theophylline on respiratory muscle efficiency (RME), 12 normal subjects were given theophylline vs placebo in a double-blind, randomized crossover protocol. Spirometry, resting energy expenditure, minute ventilation, RME and oxygen cost of breathing were measured at baseline, after taking theophylline, and after placebo. RME was calculated by dividing the added work required to breathe through a threshold load by the added energy consumed during loaded breathing. Oxygen cost of breathing was calculated by dividing the increase in oxygen consumption induced by breathing an air/carbon dioxide mixture by the associated increase in minute ventilation. RME increased from 3.3 +/- 1.6% at baseline to 7.9 +/- 3.2% after theophylline (p < 0.01) but did not change significantly after placebo (4.8 +/- 2.4%). Oxygen cost of breathing decreased from 3.9 +/- 2.4 mL O2 per liter at baseline to 1.7 +/- 0.7 mL O2 per liter after theophylline (p < 0.05) but did not change significantly after placebo (2.8 +/- 1.3 mL O2 per liter). Theophylline use was also associated with an 18% increase in minute ventilation (p < 0.01) and a 15.7% increase in resting energy expenditure (p < 0.01). Theophylline improves measured RME and reduces oxygen cost of breathing in normal subjects. These effects are offset by increases in resting energy expenditure and minute ventilation.     

The mechanism of rapid, shallow breathing after inhaling histamine aerosol in exercising dogs

In 4 unsedated, exercising dogs, we studied the effects of inhaled histamine aerosol on minute volume of ventilation, respiratory frequency, tidal volume, total pulmonary resistance, and dynamic pulmonary compliance. Inhalation (5 breaths) of 1 to 2 per cent histamine aerosols increased minute ventilation (mean, 50 per cent; p less than 0.001) by increasing respiratory frequency (mean, 166 percent; P less than 0.001), despite decreasing tidal volume (mean, 42 percent; P less than 0.0001). Total pulmonary resistance increased (mean, 200 per cent; P less than 0.001.) Breathing supplemental O2 did not affect the ventilatory response to histamine. Adding external resistive loads to a dog's airway did not simulate the pattern of rapid, shallow breathing produced by histamine. Inhalation of terbutaline prevented the changes in total pulmonary resistance and dynamic pulmonary compliance but did not alter the ventilatory response to histamine. When conduction in the cervical vagus nerves (which were implanted chronically in skin loops) was blocked by cooling, the ventilatory response to histamine was abolished. We concluded that histamine stimulates breathing by stimulation of receptors whose afferent pathways are in the vagus nerves; the effective stimulus is not bronchoconstriction but is presumably due to direct stimulation of airway receptors.