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Method-induced misclassification for a respirable dust sampled using ISO/ACGIH/CEN criteria.

The single cut measurement of exposure to respirable dust is the accepted method of exposure classification in occupational hygiene. We previously showed that actual pulmonary tissue dose may be substantially different from the dose expected, or the indicated dose, based on measurements using current single cut methodologies. We now examine exposure misclassification of workers based on any single cut respirable dust measurement using the internationally accepted ISO/ACGIH/CEN single cut respirable dust measurement criteria. Hypothetical aerosols with 12 generalized size distributions typical of the method of aerosol generation (condensation, aged condensation, mechanical low energy, mechanical high energy and mixtures thereof) were assumed. Using previously reported models for sampler penetration and pulmonary deposition, Monte Carlo simulations of actual mass dose to pulmonary tissues in comparison to the dose estimate from an ideal respirable aerosol sampler were carried out. Measurement-based indicated doses were used to classify exposures into five exposure categories and these classifications were compared with the 'true' classifications from the dose-based exposure estimates. Misclassification rates were generally severe and were greatest for aerosols with mass median aerodynamic diameter (MMAD) <1 microm (approximately 100%) and MMAD 5-15 microm (65-95%). Misclassification rates were moderate (<20%) only for extremely coarse aerosols of MMAD>15 microm. Misclassification rates for oral and nasal breathing at 750 and 1500 ml tidal volume and 15 breaths/min were similar for each aerosol examined.

Aerosols↗

Comparative study of the O(2), CO(2) and temperature effect on respiration between "Conference" pear cell protoplasts in suspension and intact pears.

The influence of the O(2) and CO(2) concentration and the temperature on the O(2) uptake rate of cool-stored intact pears and pear cell protoplasts in suspension was compared. Protocols to isolate pear cell protoplasts from pear tissue and two methods to measure protoplast respiration have been developed. Modified Michaelis-Menten kinetics were applied to describe the effect of the O(2) and the CO(2) concentration on the O(2) uptake rate and temperature dependence was analysed with an Arrhenius equation. Both systems were described with a non-competitive type of CO(2) inhibition. Due to the inclusion of gas diffusion properties, the Michaelis-Menten constant for intact pears (2.5 mM) was significantly larger than the one for protoplasts in suspension (3 microM), which was in turn larger than the Michaelis-Menten constant obtained in mitochondrial respiration measurements described in the literature. It was calculated that only 3.6% of the total diffusion effect absorbed in the Michaelis-Menten constant for intact pears, could be attributed to intracellular gas diffusion. The number of cells per volume of tissue was counted microscopically to establish a relationship between the pear cell protoplast and intact pear O(2) uptake rate. A remarkable similarity was observed: values of 61.8 nmol kg(-1) s(-1) for protoplasts and 87.1 nmol kg(-1) s(-1) for intact pears were obtained. Also, the inhibitory effect of CO(2) on the respiration rate was almost identical for protoplasts and intact pears, suggesting that protoplast suspensions are useful for the study of other aspects of the respiration metabolism.

Carbon Dioxide↗

Decreased sucrose content triggers starch breakdown and respiration in stored potato tubers (Solanum tuberosum).

To change the hexose-to-sucrose ratio within phloem cells, yeast-derived cytosolic invertase was expressed in transgenic potato (Solanum tuberosum cv. Desirée) plants under control of the rolC promoter. Vascular tissue specific expression of the transgene was verified by histochemical detection of invertase activity in tuber cross-sections. Vegetative growth and tuber yield of transgenic plants was unaltered as compared to wild-type plants. However, the sprout growth of stored tubers was much delayed, indicating impaired phloem-transport of sucrose towards the developing bud. Biochemical analysis of growing tubers revealed that, in contrast to sucrose levels, which rapidly declined in growing invertase-expressing tubers, hexose and starch levels remained unchanged as compared to wild-type controls. During storage, sucrose and starch content declined in wild-type tubers, whereas glucose and fructose levels remained unchanged. A similar response was found in transgenic tubers with the exception that starch degradation was accelerated and fructose levels increased slightly. Furthermore, changes in carbohydrate metabolism were accompanied by an elevated level of phosphorylated intermediates, and a stimulated rate of respiration. Considering that sucrose breakdown was restricted to phloem cells it is concluded that, in response to phloem-associated sucrose depletion or hexose elevation, starch degradation and respiration is triggered in parenchyma cells. To study further whether elevated hexose and/or hexose-phosphates or decreased sucrose levels are responsible for the metabolic changes observed, sucrose content was decreased by tuber-specific expression of a bacterial sucrose isomerase. Sucrose isomerase catalyses the reversible conversion of sucrose into palatinose, which is not further metabolizable by plant cells. Tubers harvested from these plants were found to accumulate high levels of palatinose at the expense of sucrose. In addition, starch content decreased slightly, while hexose levels remained unaltered, compared with the wild-type controls. Similar to low sucrose-containing invertase tubers, respiration and starch breakdown were found to be accelerated during storage in palatinose-accumulating potato tubers. In contrast to invertase transgenics, however, no accumulation of phosphorylated intermediates was observed. Therefore, it is concluded that sucrose depletion rather than increased hexose metabolism triggers reserve mobilization and respiration in stored potato tubers.

Cell Respiration↗

Methoxychlor inhibits brain mitochondrial respiration and increases hydrogen peroxide production and CREB phosphorylation.

The organochlorine insecticide methoxychlor (mxc) is an established reproductive toxicant that affects other systems including the central nervous system (CNS), possibly by mechanisms involving oxidative stress. This study tested the hypothesis that mxc inhibits brain mitochondrial respiration, resulting in increased production of reactive oxygen species (ROS). Oxygen electrode measurements of mitochondrial respiration and Amplex Red measurements of H(2)O(2) production were performed with rat brain mitochondria exposed in vitro to mxc (0-10 microg/ml) and with brain mitochondria from mice chronically exposed in vivo to mxc (0-64 mg/kg/day) for 20 days by intraperitoneal injection. In vitro mxc exposure inhibited ADP-dependent respiration (state 3) using both complex I- and II-supported substrates. Similarly, state 3 respiration was inhibited following in vivo mxc exposure using complex I substrates. H(2)O(2) production was stimulated after in vitro mxc treatment in the presence of complex I substrates, but not in mitochondria isolated from in vivo mxc-treated mice. Because previous studies demonstrated a relationship between oxidative stress and CREB phosphorylation, we also tested the hypothesis that mxc elevates phosphorylated CREB (pCREB) in mitochondria. Enzyme-linked immunosorbent assay (ELISA) measurements demonstrated that pCREB immunoreactivity was elevated by in vitro mxc exposure in the presence or absence of respiratory substrates, indicating that stimulation of H(2)O(2) production is not necessary for this effect. These multiple effects of mxc on mitochondria may play an important role in its toxicity, particularly in the CNS.

Animals↗

Effect of epidural fentanyl on neonatal respiration.

BACKGROUND: The addition of opioids to epidural infusions for laboring mothers may reintroduce the problem of neonatal depression seen with systemic opioids. The authors studied neonatal respiration and neurobehavior in newborns of mothers randomized to receive epidural analgesia with or without fentanyl. METHODS: One hundred thirty-eight women in labor received loading doses of plain bupivacaine. When pain-free, they received an infusion of either 0.125% bupivacaine alone or 0.0625% bupivacaine with 2.5 microg/ml fentanyl. After delivery, transcutaneous oxygen tension and carbon dioxide tension were recorded in the newborns every 10 s until 90 min after delivery using a transcutaneous oxygen-carbon dioxide monitor. Umbilical venous and arterial acid-base status, Apgar scores, and Neurologic and Adaptive Capacity Scores 2 h and 24 h after delivery were measured. The umbilical venous plasma fentanyl concentration was correlated with indices of neonatal respiration and welfare in the fentanyl group. RESULTS: One hundred fourteen newborns delivered vaginally were studied. In the fentanyl group, the mean (range) maternal dose of fentanyl was 184 microg (range, 53-400), and the umbilical venous fentanyl concentration was 0.077 ng/ml (range, <0.021 to 0.244). There were no significant differences between the groups for any indices of neonatal respiration or neonatal welfare, and the plasma fentanyl concentration did not correlate with any of these indices. CONCLUSIONS: The results suggest that fentanyl added to epidural bupivacaine infusions during labor does not depress neonatal respiration or adversely affect neurobehavioral scores and other indices of neonatal welfare.

Adult↗

Effects of mechanical ventilation and spontaneous respiration on hemodynamics in calves with total artificial hearts.

The effects of respiration on hemodynamics were evaluated in four Holstein calves with total artificial hearts (TAH). The electrohydraulic actuated E4T-TAH has a continuously reciprocating actuator packaged between two alternately ejecting blood pumps that passively fill. The hemodynamic parameters (right atrial pressure [RAP], left atrial pressure [LAP], pulmonary artery pressure [PAP], aortic pressure [AoP]), and right and left pump filling (Rt% fill and Lt% fill) were measured when the animal was intubated and mechanically ventilated. These measurements were repeated with spontaneous respiration after the animal was extubated. With mechanical ventilation, LAP, PAP, and AoP were significantly higher during inspiration than during expiration. However, RAP during inspiration was slightly lower than that during expiration. The Rt% fill during inspiration was significantly lower than during expiration, but Lt% fill during inspiration was significantly higher than during expiration. During spontaneous respiration, these changes were opposite to those observed during mechanical ventilation. That mechanical ventilation generates positive intrathoracic pressure during inspiration, but spontaneous respiration generates negative pressure may explain these results. The change in venous return to the right atrium caused the change in RAP to be opposite in direction to that of the other pressures.

Animals↗

Correlation of spontaneous respiration and neurologic damage in near-drowning.

Twenty-six near-drowning children were assessed for neurologic damage with the Glasgow Coma Score, and for spontaneous respirations after CPR. All children had a Glasgow Coma Score of 3 or 4; after resuscitation, 13 children had spontaneous respiration and 13 were apneic. The 13 children with spontaneous respiration suffered little or no residual neurologic impairment. Those children with apnea had severe neurologic impairment or died despite treatment. It appears that the present of spontaneous respirations correlated with surviving a near-drowning episode with minimal or no neurologic deficit and may be of benefit as a prognostic indicator.

Apnea↗

The component of physiological pupillary unrest correlated with respiration.

Components within physiological pupillary unrest have been shown to be correlated with respiration. A convolution technique has shown that a component of the unrest can be found to be correlated with respiration as the respiration is voluntarily controlled in rhythm to auditory cues over a range of respiration rates from 0.10 to 1.0 Hz. The components account for only a portion of the unrest, on the order of 0.10 mm of fluctuation in pupil diameter per cycle.

Adult↗

Grunting respirations in infants and children.

Grunting respirations are recognized as a sign of serious illness in infants and children, but have not been well studied beyond the newborn period. We present three illustrative cases and the results of a descriptive study which elucidates the causes of grunting in infants and children and suggests guidelines for assessing pediatric patients with this symptom. All patients between one month and 18 years of age who presented to the Emergency Department (ED) of The Children's Hospital of Denver during the last five months of 1992 with grunting respirations were prospectively identified, and their charts were retrospectively reviewed. The 51 pediatric patients with grunting respirations (0.3% of all patients seen in the ED) fell into three groups based upon mode of presentation: 1) 55% presented with predominantly respiratory signs and symptoms, and each one had a respiratory or cardiac condition; 2) 25% presented with high fever (greater than 38.5 degrees C) but without respiratory signs and symptoms, and all had an infectious cause (three fourths of them had an invasive bacterial disease); 3) 20% presented with neither fever nor respiratory signs or symptoms and had one of a variety of conditions which appeared to cause pain. Presenting symptoms can guide the selection of tests used to evaluate the infant or child with grunting respirations. Guidelines for evaluation are provided in this report.

Adolescent↗

Effect of slowed respiration on cardiac parasympathetic response to threat.

The present study was designed to examine the effect of voluntarily slowed respiration on the cardiac parasympathetic response to a threat: the anticipation of an electric shock. Thirty healthy college students were randomly assigned to the slow, fast, and nonpaced breathing groups (10 subjects each). Subjects in the slow and fast paced breathing groups regulated their breathing rate to 8 and 30 cpm, respectively, and those in the nonpaced breathing group breathed spontaneously. Immediately after the period of paced or nonpaced breathing for 5 minutes, the subjects were exposed for 2 minutes to the anticipation of an electric shock during breathing paced at 15 cpm. The amplitude of the high frequency (HF) component of the heart rate variability, an index of cardiac parasympathetic tone, significantly decreased during the threat in the fast and nonpaced breathing groups, whereas it was unchanged in the slow paced breathing group. No significant difference was observed among the three groups in the amplitude of respiration during the threat. Results suggest that a slowed respiration decreases the cardiac parasympathetic withdrawal response to the threat. This study provides a rationale for the therapeutic uses of the slowed respiration maneuver in attenuating the cardiac autonomic responses in patients with anxiety disorder.

Adult↗

Incidence and significance of gasping or agonal respirations in cardiac arrest patients.

PURPOSE OF REVIEW: This review examines the clinical significance of agonal respirations associated with cardiac arrest. RECENT FINDINGS: Observational data indicate that agonal respirations are frequent (55% of witnessed cardiac arrests and probably higher) and that they are associated with successful resuscitation. They also are found more commonly in ventricular fibrillation compared with other rhythms. Agonal respirations pose the greatest challenge to bystanders at the scene and to emergency dispatchers. Bystanders are often lulled into thinking the person is still breathing thus identification of cardiac arrest may be missed by the dispatcher. In a study from King County, Washington, cardiopulmonary resuscitation instructions were not provided by emergency dispatchers in 20% of cardiac arrest cases because the caller reported signs of life - typically abnormal breathing. SUMMARY: Agonal respirations occur frequently in cardiac arrest. Emergency dispatchers and the general public must be more aware of their presence and significance.

Cardiopulmonary Resuscitation↗

Patients' experiences of postoperative respirator treatment--influence of anaesthetic and pain treatment regimens.

The influences of premedication, anaesthetic agents, and postoperative sedation and pain treatment regimens on the experiences of postoperative respirator treatment of surgical patients (n = 107) have been assessed. Of the patients, 55% recalled the respirator treatment. Administration of anticholinergic drugs and halogenated anaesthetic agents was found to impair the memory process and reduce the number of recallers, and sedation in the ICU with benzodiazepines was found to decrease the number of discomforts experienced by the recalling patients. Most of the patients who received treatment postoperatively for pain, mainly by epidural administration of local anaesthetic agents and/or morphine, recalled the respirator treatment period (85%), as compared to only 50% of the patients receiving intravenous opioids. The number and type of complaints experienced by patients receiving epidural pain treatment did not, however, differ from those reported by intravenously treated patients, and no significant adverse psychological reactions seemed to occur. It is concluded that the use of mainly regional techniques, when appropriate, for pain treatment of surgical patients needing postoperative ventilatory support seems advantageous. The primary aim of relieving pain from the wound area is achieved, allowing such light intravenous sedation and pain treatment that the possibility of communication and giving comforting reassurance is maintained. Such nursing care may be more efficient in helping the patient to cope with the stressful respirator treatment situation then heavy intravenous sedation and pain treatment regimens.

Anesthetics↗

Effect on respiration of diazepam, chloropromazine and haloperidol in patients with chronic airways obstruction.

The effect on respiration of diazepam, haloperidol and chloropromazine in patients with chronic airways obstruction was studied on ten patients by the modified rebreathing method of ventilatory response to carbon-dioxide. The two parameters of the ventilatory response studied were: (a) the slope expressed as litres/minute/mmHg CO2 and (b) minute ventilation at a computed pCO2 57 mmHg (VE 57). A significant decrease in either of these parameters indicated respiratory depression. Following administration of 10 mg diazepam intramuscularly to ten patients a significant depression of respiration was observed in five patients. Administration of 50 mg chloropromazine intramuscularly to eight patients significantly depressed respiration of three patients. A significant depression of respiration was not observed in any of the ten patients given 5 mg haloperidol intramuscularly. These results indicate that the lack of significant respiratory depression from an intramuscular injection of 5 mg of haloperidol to patients with severe chronic airways obstruction makes it a safer drug, for the management of acute psychotic episodes in such patients, than 50 mg of chloropromazine or 10 mg of diazepam given intramuscularly.

Aged↗

Effects of respiration phase on ventricular defibrillation threshold in a hot can electrode system.

The impedance of defibrillation pathways is an important determinant of ventricular defibrillation efficacy. The hypothesis in this study was that the respiration phase (end-inspiration versus end-expiration) may alter impedance and/or defibrillation efficacy in a "hot can" electrode system. Defibrillation threshold (DFT) parameters were evaluated at end-expiration and at end-inspiration phases in random order by a biphasic waveform in ten anesthetized pigs (body weight: 19.1 +/- 2.4 kg; heart weight: 97 +/- 10 g). Pigs were intubated with a cuffed endotracheal tube and ventilated through a Drager SAV respirator with tidal volume of 400-500 mL. A transvenous defibrillation lead (6 cm long, 6.5 Fr) was inserted into the right ventricular apex. A titanium can electrode (92-cm2 surface area) was placed in the left pectoral area. The right ventricular lead was the anode for the first phase and the cathode for the second phase. The DFT was determined by a "down-up down-up" protocol. Statistical analysis was performed with a Wilcoxon matched pair test. The median impedance at DFT for expiration and inspiration phases were 37.8 +/- 3.1 omega, and 39.3 +/- 3.6 omega, respectively (P = 0.02). The stored energy at DFT for expiration and inspiration phases were 5.7 +/- 1.9 J and 6.0 +/- 1.0 J, respectively (P = 0.594). Shocks delivered at end-inspiration exhibited a statistically significant increase in electrode impedance in a " hot can" electrode system. The finding that DFT energy was not significantly different at both respiration phases indicates that respiration phase does not significantly affect defibrillation energy requirements.

Animals↗

Calcium-induced contraction of sarcomeres changes the regulation of mitochondrial respiration in permeabilized cardiac cells.

The relationships between cardiac cell structure and the regulation of mitochondrial respiration were studied by applying fluorescent confocal microscopy and analysing the kinetics of mitochondrial ADP-stimulated respiration, during calcium-induced contraction in permeabilized cardiomyocytes and myocardial fibers, and in their 'ghost' preparations (after selective myosin extraction). Up to 3 microm free calcium, in the presence of ATP, induced strong contraction of permeabilized cardiomyocytes with intact sarcomeres, accompanied by alterations in mitochondrial arrangement and a significant decrease in the apparent K(m) for exogenous ADP and ATP in the kinetics of mitochondrial respiration. The V(max) of respiration showed a moderate (50%) increase, with an optimum at 0.4 microm free calcium and a decrease at higher calcium concentrations. At high free-calcium concentrations, the direct flux of ADP from ATPases to mitochondria was diminished compared to that at low calcium levels. All of these effects were unrelated either to mitochondrial calcium overload or to mitochondrial permeability transition and were not observed in 'ghost' preparations after the selective extraction of myosin. Our results suggest that the structural changes transmitted from contractile apparatus to mitochondria modify localized restrictions of the diffusion of adenine nucleotides and thus may actively participate in the regulation of mitochondrial function, in addition to the metabolic signalling via the creatine kinase system.

Adenosine Diphosphate↗

Fusimotor control of muscle spindle sensitivity during respiration in the cat.

1. The two types of fusimotor neurones, dynamic and static, can be differentiated by their effects on muscle spindle afferents. We have recorded the activity of muscle spindle primary afferents from the intercostal nerves of anaesthetized or decerebrate cats. A 4 Hz sinusoidal stretch was applied to the muscle containing the spindles of interest before and after crushing the nerve proximal to the recording site to eliminate fusimotor effects. The relative activity of the dynamic and static fusimotor neurones was inferred from the change in the spindle afferents' response. 2. Some areas of intercostal muscle normally showed phasic activity linked to respiration, where as other areas of intercostal muscle showed no EMG activity under our experimental conditions. In areas of intercostal muscle lacking EMG activity, the afferents' mean rate was higher and the modulation around the mean was lower at all phases of the breathing cycle when the efferent supply was intact. This result suggests the muscle spindles were receiving a steady level of static fusimotor activity. 3. Spindle primary afferents from regions of intercostal muscle that were typically recruited during respiration had an additional increase in mean rate and modulation around the mean rate in phase with the EMG activity. This is suggestive of phasic activation of dynamic fusimotor neurones in addition to static fusimotor discharge. 4. Thus, the two types of fusimotor neurones can be activated separately by the CNS to control the sensitivity of muscle spindles. The regional differences in the recruitment patterns of fusimotor neurones parallels the functional specializations of different areas of the intercostal muscles. The temporal modifications of fusimotor activity during each respiratory cycle means that the segmental reflex gain will vary in those intercostal muscles that are active during respiration. 5. These findings regarding the CNS recruitment of the two types of fusimotor neurones during respiration are similar to those reported for the hindlimb extensors during locomotion, but differ from those reported for jaw muscles during chewing. This may reflect differing control strategies being used by the CNS to meet the unique demands of the various rhythmical movements.

Action Potentials↗

Respiration-synchronous fluctuations in stroke volume, heart rate and arterial pressure in humans.

1. Simultaneous recordings of beat-to-beat left cardiac stroke volume (SV, pulsed ultrasound Doppler), mean arterial pressure (MAP) and heart rate (HR) were obtained in ten healthy young adults during spontaneous respiration at supine rest, before and after cholinergic blockade by atropine (0.035 mg kg-1). 2. Respiration-synchronous fluctuations in SV, HR, cardiac output (CO) and MAP were quantified by spectral analysis of the recordings of each of these variables. 3. Before atropine administration, respiration-synchronous fluctuations in HR and SV were prominent. The changes in HR and SV were inversely related and variation in SV was the main source of respiratory variability in CO. Respiration-synchronous fluctuations in MAP were mainly caused by variations in CO. 4. After cholinergic blockade, respiratory HR variations were eliminated, whereas the respiratory fluctuations in SV persisted. The fluctuations in CO and MAP increased. In this situation, mechanically induced variations in SV were not counteracted by inverse HR fluctuations and the influence on CO thus increased. 5. The main source of respiratory fluctuations in MAP in supine humans is thus variation in SV, while inverse, vagally mediated HR variations tend to reduce the fluctuations in CO and MAP.

Adult↗

NITROGENOUS SUBSTRATES OF ENDOGENOUS RESPIRATION IN PSEUDOMONAS AERUGINOSA.

Gronlund, Audrey F. (University of British Columbia, Vancouver, Canada) and J. J. R. Campbell. Nitrogenous substrates of endogenous respiration in Pseudomonas aeruginosa. J. Bacteriol. 86:58-66. 1963.-The nature of the nitrogenous reserves of Pseudomonas aeruginosa that are oxidized during endogenous respiration was studied by following the changes in the chemical constituents and in the distribution of radioactivity of starving cells that had been grown on C(14)-labeled substrates. The total protein and nucleic acid of Warburg vessel contents decreased during starvation. Deoxyribonucleic acid increased slightly, whereas ribonucleic acid (RNA) decreased. C(14)O(2) was evolved from endogenously respiring cells specifically labeled in the nucleic acid fraction and from cells specifically labeled in the protein fraction. Chemical fractionation of C(14)-labeled cells showed a decrease in hot trichloroacetic acid-soluble and -insoluble compounds, indicating that the C(14)O(2) arose from the degradation of RNA and protein and not free pool compounds. A decrease in ribosomal RNA and protein was evident from physical fractionations of starved, labeled cells. An enzyme responsible for the initiation of ribosomal degradation was found to be associated with the ribosome fraction. It was concluded that oxidation of the ribonucleo-protein during endogenous respiration may be a general phenomenon in microorganisms.

Ammonia↗