Breathing Pure Oxygen Research Articles

Ventilatory instability in patients with congestive heart failure and nocturnal Cheyne-Stokes breathing.

Many of the factors that appear to cause Cheyne-Stokes Breathing (CSB) in sleeping patients with congestive heart failure (CHF) are present during wakefulness. We studied the stability of ventilatory pattern in nine awake CHF patients (left ventricular ejection fraction 9-48%) who demonstrated CSB only while asleep and compared results with 13 age-matched normals. The test involved brief (30-50-second) exposure to hypoxia (end-tidal PO2 = 55 Torr) followed by breathing pure oxygen. During hypoxia, ventilation increased about 40% above air breathing control in both groups, whereas end-tidal CO2 declined to 92% of control in both groups. During hyperoxia, however, breathing pattern differed between groups. In the normals, ventilation gradually declined to air-breathing levels and did not significantly undershoot. In the patients, ventilation dropped more rapidly to baseline and an overshoot was present with ventilation being 72% and air-breathing control at 45 seconds of hyperoxia. Circulatory delay was calculated from the time interval between alveolar hypoxia and in increase in ventilation, and when corrections for circulatory delay were applied to ventilation during hyperoxia the differences between groups increased in that the patients' ventilation was less than baseline immediately after the delay. In the normals, the gradual decline in hyperoxic ventilation probably represents the decay of short-term potentiation (STP) activated by hypoxic hyperventilation. Results in the patients were compatible with absence of such STP decay, but could also have been due to a reduction in ventilatory drive early in hyperoxia related to prolonged circulation times.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen tension mapping with F-19 echo-planar MR imaging of sequestered perfluorocarbon.

The authors used fluorine-19 inversion-recovery (IR) echo-planar imaging (EPI) to map oxygen tension on the basis of the spin-lattice relaxation rate (R1) of sequestered perfluorocarbon. R1 measured with IR-EPI varied as a linear function of oxygen tension and temperature, and the relationship agreed well with earlier spectroscopic findings. Oxygen tension maps of a mouse that had received a dose of perflubron emulsion were acquired before, during, and after the mouse breathed pure oxygen. Results showed low liver oxygen tension during air breathing, which increased during breathing of pure oxygen, with distinct regional heterogeneity, to 8-17% atm (60-130 torr [8.0-17.3 kPa]).

Erythropoietin Secretion in Patients with Chronic Renal Failure after Pure Oxygen Breathing

The present study aimed to assess the relationship between erythropoietin (EPO) secretion and hyperoxemia in uremic patients. In 19 patients with chronic renal failure (10 were hemodialyzed and 9 were not dialyzed) and in 13 healthy subjects plasma erythropoietin levels were assessed during 6 h of air breathing and a second time during 2 h of pure oxygen breathing and during 4 h after discontinued oxygen breathing. Under basal conditions, uremic patients showed higher plasma erythropoietin levels (39.85 +/- 5.86 mU/ml in hemodialyzed and 29.05 +/- 4.94 mU/ml in nondialyzed patients) as compared with healthy controls (21.04 +/- 1.77 mU/ml). Pure oxygen breathing was followed by a significant decline of plasma EPO levels both in patients with chronic renal failure and in the control group. However, this decline was significantly less marked and of longer duration in chronic renal failure patients than in healthy controls.

Mechanisms of Impaired Arterial Oxygenation in Patients With Liver Cirrhosis and Severe Respiratory Insufficiency: Effects of Indomethacin

The mechanisms of impaired arterial oxygenation that occur in certain patients with chronic liver cirrhosis are still debated. In the present study, we investigated nine cirrhotic patients with severe respiratory disability (mean PaO2, 64 +/- 5 mm Hg), using the inert gas elimination technique to assess the distribution of ventilation-perfusion (VA/Q) ratios. We also determined shunt fraction during pure oxygen breathing, both in supine and sitting positions. To test the hypothesis that vasodilating prostaglandins could contribute to alter gas exchange in such patients with cirrhosis, we examined the hemodynamic and gasometric responses to indomethacin, 50 mg IV, in six of them. During baseline conditions, patients had high cardiac index (CI, 4.9 +/- 0.2 L/min/m2), and low pulmonary (PVR, 1.78 +/- 0.37 mm Hg/L/min/m2) or systemic (SVR, 17.7 +/- 1.15 mm Hg/L/min/m2) vascular resistances. Large intrapulmonary shunt fraction was documented in each patient with a mean value of 19.6 +/- 2.7 percent. Small perfusion in low VA/Q areas was associated with shunt in only three patients (2.5 to 5.3 percent of blood flow). Arterial PO2 was negatively related to shunt (p < 0.01) and to the dispersion of blood flow distribution (p < 0.02). There was no difference between measured and predicted PaO2. Shunt estimates from the inert gas and the 100 percent O2 breathing techniques were, respectively, 19.6 +/- 2.7 percent and 21.7 +/- 3.0 percent. During 100 percent oxygen breathing, changing from supine to sitting position decreased PaO2 from 401 +/- 50 to 333 +/- 64 mm Hg (p < 0.02), while O2 shunt remained unchanged, arteriovenous difference widened, and mixed venous PO2 decreased, from 61 +/- 3 to 47 +/- 4 mm Hg (p < 0.001). Indomethacin did not improve gas exchange or VA/Q distribution and did not affect systemic or pulmonary hemodynamics. The results show that in cirrhotic patients with severe respiratory disability, intrapulmonary shunting is the main determinant of impaired gas exchange, with no evidence of a defect in oxygen diffusion or an extrapulmonary shunt. Vasodilating prostaglandins do not appear to contribute to these alterations.

Retinal vessel autoregulation in sickle cell patients.

We tested retinal vessel autoregulation in 16 sickle cell patients and 6 controls by computer-assisted measurements of constriction of the superior and inferior temporal veins and arteries after pure oxygen breathing. Compared to the controls and corrected for age, we found a decrease of vasoconstriction in three of the four vessels measured in the sickle cell group, which was statistically significant only for the superior temporal artery (P 0.009). The number of patients was too small to allow a separate analysis of possible contributory factors within the sickle cell group, such as sickle cell hemoglobin subtype and extent of retinal ischemia. Our findings indicate a factor not yet well known in the pathophysiology of sickle cell disease: an abnormality of local microvascular control.

The external respiration and gas exchange in space missions

Literature data and results of our own studies into an effect of micro- and macro-gravity on an external respiration function of man are presented. It is found that in cosmonauts following the 7–366 day space missions there is an enhanced tendency associated with an increased flight duration toward a decrease in the lung volume and breathing mechanics parameters: forced vital capacity of the lungs (FVC) by 5–25 percent, peak inspiratory and expiratory (air) flows (PIF, PEF) by 5–40 percent. A decrease in FVC appears to be explained by a new balance of elastic forces of the lungs, chest and abdomen occuring in microgravity as well as by an increased blood filling and pulmonary hydration. A decline of PIF and PEF is probalbly resulted from antigravitational deconditioning of the respiratory muscles with which a postflight decreased physical performance can in part be associated. The ventilation/perfusion ratios during orthostasis and +G Z and +G X accelerations are estimated. The biophysical nature of developing the absorption atelectases on a combined exposure to accelerations and 100% oxygen breathing is confirmed. A hypothesis that hypervolemia and pulmonary congestion can increase the tendency toward the development of atelectases in space in particular during pure oxygen breathing is suggested. Respiratory physiology problem area which is of interest for space medicine is defined. It is well known that due to present-day technologic progress and accomplishments in applied physiology including applied respiration physiology there currently exist sophisticated technical facilities in operation maintaining the life and professional working capacity of a man in various natural environments: on Earth, under water and in space. By the way, the biomedical involvement in developing and constructing such facilities has enabled an accumulation of a great body of information from experimental studies and full-scale trails to examine the effects of the changed environments both and its individual systems including an external respiration function. In this case, it should be remembered that the external respiration system has some physiological and morphological properties due to which the body systems are particularly subjected to environmental effects. Thus, according to figurative comparison by Evald Veible a contact area of the lungs with an external environment i.e. an alveolar surface is large and equaled approximately to tennis-court size, as the alveolocapillary membrane thickness is negligible and amounts to one fiftieth of a writing-paper sheet [1]. From this it follows that such a fine and highly organized structure must be extremely dependent upon any external exposures including gravitational ones since from the physical viewpoint of physics the lungs represent a quasiconical three-dimensional elastic body suspended in the thoracic cavity and in which there occur the gravity-induced internal tensions incrementing in a base-to-apices direction. As a result of these tensions, in the lungs various physical gradients: hydrostatic, pleural and transpulmonary pressures, pulmonary time constant, vertical gradient of the volume and structure of alveoli, etc. are developed.

Détresse respiratoire chez une héroïnomane séropositive pour le virus de l'immunodéficience humaine

A 31-year-old woman, heroin addict since ten years, and infected by the human immunodeficiency virus (HIV) since one year, was admitted to the intensive care unit for respiratory failure (PaO 2 = 40 mmHg and PaCO 2 = 14.8 mmHg, despite breathing pure oxygen). She had been followed up for 6 months for increasing dyspnoea due to chronic cor pulmonale for which no satisfactory explanation had been put forward. Artificial ventilation with 8 cmH 2O positive end-expiratory pressure and 100 % oxygen was completely inefficient. She died within a few hours. Postmortem lung biopsy revealed talc particles within interalveolar walls and alveolar macrophages as well as the expected alterations in blood vessels. Pulmonary hypertension due to talc microemboli is a well-known cause of respiratory failure in heroin addicts. Such a diagnosis should not be overlooked in a patient infected with HIV. Respiratory failure may not be only due to opportunist infections, or tumours related to the HIV infection.

Existence of leukotoxin 9,10-epoxy-12-octadecenoate in lung lavages from rats breathing pure oxygen and from patients with the adult respiratory distress syndrome.

Pulmonary influxed neutrophils have been suggested to be involved in the development of hyperoxia-induced lung injury. We recently revealed that a highly toxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named leukotoxin. Because hyperoxia-induced lung injury is a model of adult respiratory distress syndrome (ARDS), this study was designed to investigate whether or not leukotoxin is involved in the genesis of pulmonary oxygen toxicity and ARDS. After exposure to hyperoxia for 60 h, rats showed acute pulmonary edema, which was evidenced by increased lung weight, albumin concentrations, and angiotensin-converting enzyme (ACE) activities in lung lavages. These changes were correlated with an increased number of neutrophils. We detected leukotoxin in lung lavages of rats after exposure to hyperoxia for 60 h by high performance liquid chromatography and gas-chromatography/mass spectrometry. After intravenous injection of leukotoxin (100 mumol/kg) to rats, acute edematous lung injury occurred showing increases in lung weight, lung lavage albumin concentrations, and lung lavage ACE activities. In the lung lavages obtained from 5 patients with ARDS, significant increases in albumin concentrations and ACE activities were observed compared with those from subjects without pulmonary disease. Moreover, considerable amounts of leukotoxin, 38.5 +/- 21.9 nmol/lung lavage, were observed in the lavages from patients with ARDS. These findings suggest that leukotoxin plays an important role in the genesis of acute edematous lung damage in pulmonary oxygen toxicity, and that leukotoxin also links with the development of lung injury observed in patients with ARDS.

Understanding the meaning of the shunt fraction calculation.

The pulmonary shunt fraction (Qs/Qt) is frequently calculated in critically ill patients to monitor the effectiveness of pulmonary oxygenation. The breathing of pure oxygen often results in higher calculated Qs/Qt values that have been attributed to the development of atelectasis, ventilation-perfusion imbalance, or both. To interpret properly the changes in calculated Qs/Qt that occur when the inspired oxygen fraction is altered, the changes produced in all the variables affecting Qs/Qt must be known. This tutorial presents an in-depth analysis of the four variables affecting the calculation of Qs/Qt: VO2 (oxygen uptake), Qt (cardiac output), Cc'O2 (oxygen content in pulmonary end capillaries), and CvO2 (oxygen content in mixed venous blood). These variables are related according to the following equation, which is derived by combining the Fick and the classic shunt equations: Qs/Qt = 1 - [(VO2/Qt)/(Cc'O2 - CvO2)]. Three-dimensional surface representations relating these variables are also presented to help the reader understand the effects of these variables on the calculated Qs/Qt.

Research on hydroxyl radicals (.OH) in plasma under hyperbaric oxygen exposure

Hyperbaric Oxygen Therapy (HBO) is a remarkably effective therapy against hypoxic disorders; however, problems concerning the safety of this therapy still remain. One method of counteracting the toxicity of HBO is to limit the magnitude of compressed pressure and the exposure time to avoid the onset of acute conditions such as convulsions. A reliable indicator of the toxicity is also needed.The hydroxyl radical (sdot;OH) is the fastest reacting and most injurious radical, so it was selected as the target for the evaluation of HBO in this study.Rabbits were exposed to HBO conditions for between one and four ATA (atmospheres absolute) for 60min., and the hydroxyl radical was studied with the lapse of time by electron spin resonance (ESR).As a result, it was determined that, in conditions above 3 ATA, breathing pure oxygen for 60min. creates problems even if acute oxygen toxicity is not recognized.It is, thus, necessary to establish standards for safety and adaptability of HBO.The advantages of HBO have been discussed; however, the responses of oxygen free radicals should be studied more carefully. It is also essential to determine the oxygen toxicity. Such studies may be expected to give us data which can be of great use in HBO.

Mechanism of oxygen toxicity in rat lungs.

This study was designed to investigate the mechanism responsible for lung injury in rats induced by oxygen breathing. After oxygen exposure for 60 h the rats began to die, and mortality reached 85% after 72 h of exposure. After 48 h and 60 h of oxygen exposure, the microsomal lipid peroxide (LPO) level was increased significantly compared to control rats. The microsomal ATP-dependent calcium uptake was decreased significantly after 48 h and 60 h of oxygen exposure when compared with the control. The endogenous phospholipase activity in lung membrane fractions was elevated significantly after 48 h and 60 h of oxygen exposure, respectively. After 48 h and 60 h of oxygen exposure, leukotriene B4 (LTB4) level in lung lavages was also increased significantly compared with the control. The number of polymorphonuclear leukocytes (PMN) in lavages was increased significantly after 60 h of oxygen exposure. Administration of verapamil prevented the elevation of the phospholipase activity, LTB4 level and the number of PMN, and reduced the mortality rate to 40% at 72 h, while it did not affect the formation of LPO or the depression of the calcium uptake. Calcium is the essential activator of phospholipase. Therefore, decreased calcium uptake in lung microsomes is considered to induce disturbance in intracellular calcium regulation, which, in turn, causes the activation of phospholipase, resulting in the elevation of LTB4, a potent chemotactic agent for PMN. Verapamil could prevent the disturbance of intracellular calcium regulation by inhibiting calcium influx and the activation of phospholipase. The enhanced phospholipase activity and associated elevation of lipoxygenase product are responsible for lung damage induced by pure oxygen breathing.

Hyperoxia Produces Neuronal Necrosis in the Rat

Widespread cerebral neuronal necrosis occurred in newborn Sprague-Dawley rats submitted to three hours of pure oxygen (100% O2) at normal atmospheric pressure. Neuronal necrosis (NN) was most severe in the immediate newborn period and less marked with advanced maturation. It was minimal and different in its morphological characteristics in rats 10, 15 and 20 days old, and in adults breathing pure oxygen at normal atmospheric pressure for three hours. In the newborn rat, hyperoxemic NN was different in topography and cytopathology from that induced by hypoxia in the same animals. Hyperoxemic NN was similar to the NN described in human premature infants submitted to episodic hyperoxemia. Neuronal damage with karyorrhexis was most prominent in the subiculum of the hippocampus, thalamus, reticular nuclei of the brain stem and the granular cells of the cerebellum. Ultrastructural studies demonstrated nuclear and cytoplasmic membrane damage in neurons and the cellular accumulation of electron-dense lipid droplets. The pathogenesis of NN produced by hyperoxia in the human premature newborn infant may be related to lipid peroxidation of cell membranes such as that induced by oxygen-free radicals in other experimental and in vitro studies, when the anti-oxidant cellular defenses (mainly enzymes such as superoxide dismutase) are overwhelmed.

Biosynthesis of leukotoxin, 9, 10-epoxy-12 octadecenoate, by leukocytes in lung lavages of rat after exposure to hyperoxia

In lung lavages of rat after pure oxygen breathing, a toxic linoleate peroxide, 9, 10-epoxy-12-octadecenoate, and its isomer, 12,13-epoxy-9-octadecenoate were detected by HPLC analyses. The epoxide(s) was demonstrated to be biosynthesized by incubating lingleate with leukocytes collected from lung lavages, thus nominated to be leukotoxin. The chemical structures of leukotoxin and its isomer were determined by gas-chromatography/mass spectrometry and nuclear magnetic resonance measurements. Leukotoxin showed a potent uncoupling activity to rat liver mitochondrial respiration and a dose-dependent relaxation of rat stomach smooth muscle. These findings were discussed with ‘oxygen toxicity’ on the lung.

MR imaging of the lung using liquid perfluorocarbons.

Certain perfluorocarbon (PFC) compounds, commonly used as the oxygen transport components of "blood substitutes," may be breathed as neat liquids with survival because of their chemical inertness and their high solubility for oxygen and carbon dioxide. In addition, the paramagnetism of oxygen reduces the fluorine T1 value according to an inverse relationship allowing a potential method of monitoring PO2 gradients in vivo. This article presents the results of magnetic resonance (MR) imaging of the lungs of mice and rats following breathing of four PFC liquids (FC-43, FC-75, PFOB, APF-215). The images presented were obtained at two magnetic field strengths (0.66 and 0.14 T) under conditions of breathing either ambient air or pure oxygen. Spin-lattice relaxation times (T1) for the PFCs are measured both in vitro and in vivo (in the lungs) as a function of the state of oxygenation. A MR image signal strength enhancement of up to 90% is demonstrated in vivo under conditions of pure oxygen breathing.

Ventilation-Perfusion Relationships in Symptomatic Asthma: Response to Oxygen and Clemastine

Continuous distributions of ventilation-perfusion (VA/Q) ratios were measured in ten subjects with moderately severe symptomatic asthma. Six of the subjects had only minimal VA/Q inequality (mean log SD of bloodflow 0.5) despite having airways obstruction similar to that in the four subjects with marked VA/Q inequality (mean log SD of bloodflow 1.0). The six patients with minimal VA/Q inequality developed marked widening of their VA/Q distributions while breathing 100 percent oxygen (mean log SD bloodflow 1.1), and four of these patients maintained more modest widening after receiving an intravenous antihistamine, clemastine (mean log SD bloodflow 0.75). The four subjects with a wide control VA/Q distribution showed smaller changes while breathing pure oxygen and no change after receiving clemastine. FEV1 improved with clemastine treatment in the first four patients only. The results suggest that the majority of patients with moderately severe asthma have compensatory pulmonary vasoconstriction, causing better VA/Q matching which is responsive to hypoxia and, possibly, histamine. The data demonstrate a relationship between active compensatory vasoconstriction and airway sensitivity to antihistamine.

Modulation of tissue fibrinolysis from hypoxia and hyperoxia

The effects from alterations in inspired oxygen tension on the fibrinolytic activity in vessel walls was studied in rats. Tissue plasminogen activator activity was measured semiquantitatively with the histochemical technique. During severe hypoxic conditions (FIO 2 = 0.05) the fibrinolytic activity in the aorta was significantly reduced as compared to control animals. At 24 hours with slightly higher oxygen tension (FIO 2 = 0.08) the activity was increased. When breathing pure oxygen (FIO 2 = 1.0) the fibrinolytic activity was increased in the aorta after 8 hours. Following chronic hypoxia for 6 weeks (FIO 2 = 0.1) the activity in the caval vein was increased. Changes in inspired oxygen tension thus affected the endothelial cells and changed their expression of plasminogen activator activity.

Age-related reductions in cerebral vasomotor reactivity and the law of initial value: a 4-year prospective longitudinal study.

A group of 51 neurologically normal, middle-aged and elderly volunteers (aged 35-86 years; mean age 63.24 years) with and without risk factors for stroke were given annual tests of cerebral vasomotor reactivity to assess any changes in the cerebral vascular capacitance associated with advancing age that might alter cerebral vasomotor reactivity. Cerebral vasomotor reactivity was estimated as the difference in bihemisphere gray matter CBF measured by the 133Xe inhalation method in the steady state breathing room air, followed by a second measurement during inhalation of 100% oxygen. There were significant and progressive reductions in cerebral vasomotor reactivity during the 4-year longitudinal study. Positive linear correlations were apparent between initial steady-state mean bihemisphere gray matter CBF levels and degrees of vasomotor reactivity, suggesting that the Law of Initial Value plays an important role. This should be borne in mind when analyzing scores of cerebral vasomotor reactivity. In the present communication, analysis of covariance was used to correct for influences of initial CBF levels on vasomotor responses tested while breathing pure oxygen.

Effects of breathing pattern and oxygen upon the alveolar arterial oxygen pressure difference in lung disease.

It was suggested by analysis of theoretical lung models that low V/Q units are unstable and can be converted into shunt by breathing O2. We tested this theory in 21 subjects with various lung diseases (mostly chronic obstructive pulmonary disease) by having them breathe O2. We also increased the tidal volumes in these patients to see whether this maneuver could prevent the development of shunt. We found that mean P(A-a)O2 increased from 30 +/- 2.8 (mean +/- SEM) Torr breathing room air to 135 +/- 20.7 Torr breathing O2 for 10 min (p less than 0.0001), to 124 +/- 20.4 Torr breathing O2 for 20 min (p less than 0.0001), and to 125 +/- 19.0 Torr breathing oxygen with inspiratory capacity breaths (p less than 0.0001). The corresponding shunt increased from about 2.8% of the cardiac output to 7.9 +/- 1.01, 7.3 +/- 1.03 and 7.3 +/- 0.98%, respectively. We conclude that: (1) breathing pure oxygen can convert low V/Q units to shunt, hence measurement of P(A-a)O2 and shunt by oxygen technique will overestimate the actual values; (2) 10 min of oxygen breathing will cause complete atelectasis of low V/Q units, and (3) increased tidal volume does not prevent absorptive atelectasis.

Effects of 100% oxygen on lung vascular function in awake sheep.

The purpose of this study was to define the time course of pulmonary toxicity during continuous breathing of 100% oxygen in adult sheep. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange, and for collection of lung lymph. Tracheostomies allowed accurate delivery of either 100% oxygen, compressed air, or hypoxic gas. Six sheep breathed 100% oxygen for 72-96 h, and four sheep breathed compressed air for 96 h. In addition to hypoxic challenges [fractional concentration of inspired O2 (FIo2) = 0.12], some sheep received prostaglandin H2 (PGH2)-analogue infusions to further assess pulmonary vascular reactivity. Lung lymph and blood chemotactic activity were measured by granulocyte migration in modified Boyden chambers. Postmortem lung water content and light microscopy were used to measure pulmonary edema. All sheep breathing 100% oxygen died between 72 (n = 2) and 96 h (n = 4). Sheep breathing oxygen demonstrated lung toxicity by measurements of 1) a fourfold increase in flow of protein-rich lung lymph, 2) increased alveolar-arterial difference in Po2 (greater than 20 Torr on FIo2 = 0.21) and hypercapnic acidemia, and 3) a mean extravascular lung water/dry lung weight of 5.7 (controls = 3.3), and histological evidence of interstitial and alveolar edema. Chemotactic activity in lung lymph at base line increased eightfold within 72-96 h of oxygen breathing. In sheep breathing oxygen, the hypoxic pressor response decreased by 50% at 48 h, and by 72-96 h there was a total absence of hypoxic vasoconstriction. There was no increase in lung lymph prostacyclin metabolite, and sodium meclofenamate did not restore the pressor response. In sheep breathing compressed air none of these changes in pulmonary vascular reactivity, lymph flow, or chemotactic activity occurred. We conclude that prolonged breathing of pure oxygen causes pulmonary edema by increasing lung vascular permeability and that respiratory failure results from both edema and loss of pulmonary vascular reactivity.

The Retreat of Multiple Sclerosis

The Retreat of Multiple Sclerosis