Changes in the blood-air barrier of the lungs in hyperthermia

The influence of hyperthermia on the ultrastructure of lung air-blood barrier (ABB) was studied in experiments on dogs. It was shown that in hyperthermia both mean arithmetic and mean harmonic thickness of ABB were increased. The lung capillary endothelial layer was the most thick ABB layer, in which severe micropinocytosis could be observed. Marked destructive changes were noted in lung alveolar epithelial ABB layer up to the appearance of cell content in alveolar space and denudation of the epithelial basal membrane.     

Ultrastructure of the blood-air barrier in comparison with the indices of surfactant surface activity

Ultrastructure of the air-blood barrier and surface surfactant activity were studied at different time periods of nonspecific inflammation of the lungs in guinea pigs. The animals were sacrificed 3 days, 2 weeks and 1, 2 and 4 months after beginning of the experiment. It has been demonstrated that in early periods of lung inflammation there was edema of all components of the air-blood barrier. Subsequent development of inflammation is accompanied by surface activity decrease associated with dystrophic changes in the epithelial cells of alveoli. At the same time there are compensatory changes in the lungs, directed to eliminate deficiency of surfactant.     

Evaluation of the efficacy of extracorporeal membrane oxygenation of animals with acute respiratory insufficiency

The efficiency of extracorporeal membrane oxygenation was studied for 2-3 hours in experiments on dogs with severe ventilatory respiratory failure. Extracorporeal oxygenation led to the decrease in arterial hypoxaemia and hypercapnia in animals. However, the variables did not reach the initial levels and were closer to normal values during veno-venous and not veno-arterial perfusion. During extracorporeal membrane oxygenation total systemic blood flow exceeded the initial level irrespective of the means of perfusion and total oxygen transport did not decline lower than the initial level. At the same time during veno-arterial perfusion oxygen delivery provided by the cardiac output decreased almost two-fold by the second hour of perfusion. This might be the reason for inadequate oxygen delivery to the brain and heart. 67% and 71% of animals survived after veno-arterial and veno-venous perfusion, respectively.     

Control of hypoxia using apneic oxygenation with extrapulmonary membrane elimination of CO2

The peculiarities and conditions of optimal gas exchange for arresting hypoxia during prolonged (3 hours) apnoea or bradypnoea were experimentally studied in 34 dogs, using the method of apnoea oxygenation and extrapulmonary membrane removal of CO2 on "Sever" membrane gas-exchanger. It was shown that successful arrest of severe ventilation disorders of respiration by this method depends on precise registration and skillful use of the factors influencing oxygenation and CO2 removal in membrane gas-exchanger connected with peripheral arteriovenous or venovenous shunts.     

Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise.

To determine if fatigue at maximal aerobic power output was associated with a critical decrease in cerebral oxygenation, 13 male cyclists performed incremental maximal exercise tests (25 W/min ramp) under normoxic (Norm: 21% Fi(O2)) and acute hypoxic (Hypox: 12% Fi(O2)) conditions. Near-infrared spectroscopy (NIRS) was used to monitor concentration (microM) changes of oxy- and deoxyhemoglobin (Delta[O2Hb], Delta[HHb]) in the left vastus lateralis muscle and frontal cerebral cortex. Changes in total Hb were calculated (Delta[THb] = Delta[O2Hb] + Delta[HHb]) and used as an index of change in regional blood volume. Repeated-measures ANOVA were performed across treatments and work rates (alpha = 0.05). During Norm, cerebral oxygenation rose between 25 and 75% peak power output {Power(peak); increased (inc) Delta[O2Hb], inc. Delta[HHb], inc. Delta[THb]}, but fell from 75 to 100% Power(peak) {decreased (dec) Delta[O2Hb], inc. Delta[HHb], no change Delta[THb]}. In contrast, during Hypox, cerebral oxygenation dropped progressively across all work rates (dec. Delta[O2Hb], inc. Delta[HHb]), whereas Delta[THb] again rose up to 75% Power(peak) and remained constant thereafter. Changes in cerebral oxygenation during Hypox were larger than Norm. In muscle, oxygenation decreased progressively throughout exercise in both Norm and Hypox (dec. Delta[O2Hb], inc. Delta [HHb], inc. Delta[THb]), although Delta[O2Hb] was unchanged between 75 and 100% Power peak. Changes in muscle oxygenation were also greater in Hypox compared with Norm. On the basis of these findings, it is unlikely that changes in cerebral oxygenation limit incremental exercise performance in normoxia, yet it is possible that such changes play a more pivotal role in hypoxia.     

Predictors of mortality in patients successfully weaned from extracorporeal membrane oxygenation

Purpose

Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients, such as those with life-threatening respiratory failure or post-cardiotomy cardiogenic shock. This study compares the predictive value of Acute Physiology, Age, and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Organ System Failure (OSF) obtained on the first day of ECMO removal, and the Acute Kidney Injury Network (AKIN) stages obtained at 48 hours post-ECMO removal (AKIN_48-hour) in terms of hospital mortality for critically ill patients.

Methods

This study reviewed the medical records of 119 critically ill patients successfully weaned from ECMO at the specialized intensive care unit of a tertiary-care university hospital between July 2006 and October 2010. Demographic, clinical, and laboratory data were collected retrospectively as survival predictors.

Results

Overall mortality rate was 26%. The most common condition requiring ECMO support was cardiogenic shock. By using the areas under the receiver operating characteristic (AUROC) curve, the Sequential Organ Failure Assessment (SOFA) score displayed good discriminative power (AUROC 0.805±0.055, p<0.001). Furthermore, multiple logistic regression analysis indicated that daily urine output on the second day of ECMO removal (UO_{24–48 hour}), mean arterial pressure (MAP), and SOFA score on the day of ECMO removal were independent predictors of hospital mortality. Finally, cumulative survival rates at 6-month follow-up differed significantly (p<0.001) for a SOFA score≤13 relative to those for a SOFA score>13.

Conclusions

Following successful ECMO weaning, the SOFA score proved a reproducible evaluation tool with good prognostic abilities.     

Platelets and leukocytes in the lungs after acute hypobaric hypoxia

To determine if decompression from sea level causes aggregation and embolization of platelets or leukocytes to the lungs, we have measured the accumulation of 51Cr-labeled platelets or 111In-labeled leukocytes in the lungs of rabbits decompressed to 440 or 350 Torr for 18 or 40 h. To be certain that any increased accumulation of labeled platelets (or leukocytes) in the lungs was not just caused by an increased pulmonary blood volume we also labeled the rabbits red blood cells with 59Fe. There was no detectable accumulation of labeled platelets in the lungs on decompression. In control animals there were 22 times as many labeled leukocytes in the lungs as could be accounted for by the volume of blood in the lungs. In experimental animals at 326 Torr for 18 h this figure was reduced to 13.6. Hypobaric hypoxia caused an increase in circulating granulocytes from a mean of 3.3 +/- 1.6 X 10(9)/l to 5.3 +/- 2.1 X 10(9)/l. (P less than 0.005). Our results suggest that decompressions to 6,100 m for 18 h does not cause platelet sequestration in the lungs but does cause a significant reduction in leukocytes in the lungs and a peripheral granulocytosis.     

Ultrastructure of alveolar bone during tooth eruption in the dog

Previous work from our laboratories has established that eruption of the permanent mandibular premolars in dogs is dependent upon the presence of the dental follicle and that it involves resorption of alveolar bone and the roots of the deciduous predecessor above and formation of alveolar bone below the developing crown. This study illustrates the topography of the bone surfaces of the crypt by scanning electron microscopy and the ultrastructure of the cells on alveolar bone surfaces during tooth eruption. Above the developing crown where the eruption pathway forms, the bone surface is a pitted sheet, the characteristic topographic feature of bone resorption; between the crown and the mandibular canal, the bone surface has numerous interconnecting trabeculae. Transmission electron microscopy of bone cells lining the eruption pathway area of the crypt showed numerous osteoclasts with adjacent mononuclear cells. Both cell types contained specific, membrane-bound cytoplasmic vesicles shown by the work of others to be characteristic features of osteoclasts and their precursors. Basal trabeculated bone in the crypt was covered by plump osteoblasts. These data show that the metabolic events in alveolar bone associated with tooth eruption have the appropriate cellular and bony surface correlates and that the suspected control of alveolar bone resorption by the dental follicle may be mediated by its recruiting and directing to adjacent bone surfaces the mononuclear precursors of osteoclasts.     

Gas mixing in the airways of dog lungs during high-frequency ventilation

Washout of insoluble inert test gases of different diffusivity (He and SF6 or He and Ar) from dog lungs was studied during high-frequency ventilation (HFV). Test gas equilibrium and subsequent washout were performed with HFV, succeeding measurements being performed at different stroke volumes (1.5-2.5 ml/kg body wt), oscillation frequencies (10-30 Hz), and with different lung volumes (32-74 ml X kg-1). Test gas concentrations were continuously measured by a mass spectrometer. The time course of washout could be described as the sum of two exponentials. There were no consistent differences in the time courses of washout between He and SF6 or between He and Ar. It is concluded that gas mixing in the airways during HFV is not significantly limited by diffusion, and this is suggested to apply during HFV to steady-state transport of respiratory gases (e.g., O2 and CO2) as well as to the transient state of inert gas washout.     

Pulmonary capillary recruitment during airway hypoxia in the dog.

To study the effect of hypoxia on the pulmonary capillaries, windows were inserted in the chest wall of 9 pentobarbital-anesthetized dogs. A microscope with an image-superimposing device was used to make drawings of the perfused capillaries. Summed lengths of individual perfused capillaries in the drawing were determined with a map-measuring tool. Total capillary length was constant between PaO2 of 160 and 70 Torr. As PaO2 fell below 70 Torr, recruitment of previously unperfused capillaries occurred in every case; at PaO2 of 40 Torr, the total length of perfused capillaries was about 4 times greater than during normoxia. There was no correlation between the recruitment of capillaries and alterations in left atrial pressure, only a weak correlation with cardiac output changes, but a very strong correlation with increased pulmonary artery pressure. This implies that recruitment was probably caused by vasoconstriction within the lung.     

Functional morphology of the bronchovascular barrier of the human lungs during various age periods

Cellular components of the bronchovascular barrier have been studied in human lungs obtained after death of some patients with acute and chronic lung inflammatory diseases, hypertonic disease, atherosclerosis and chronic glomerulonephritis. Certain oxidative-reductive and hydrolytic enzymes, including NAD-, NADP- diaphorases, lactic dehydrogenase, acid and alkaline monophosphoesterase, ATP-ase, adenylate cyclase and nonspecific esterase were evaluated quantitatively after the histochemical processing of the specimens for the above reactions. Correlation analysis was performed for the bronchial epithelium, endotheliocytes, lymphocytes, plasma and mast cells, as well as macrophages and polymorphonuclear leucocytes. The results showed that there was a significant shift in some of the measured enzymic activities. Moreover, the correlations between different quantitative data were noted and these correlations changed with age. The increase in "rigidity" of the correlations in the elements of the bronchovascular barrier has been demonstrated during the process of ageing.     

The surfactant system and structure of the respiratory portion of the lungs during de-adaptation following a single exposure to acute pressure chamber hypoxia

The effect of acute pressure chamber hypoxia on the surfactant system and respiratory segment structure of the lungs were studied in rats by physical, fluorescent microscopic and morphometric methods. Acute hypoxia decreases surface activity, induces changes in cellular and extracellular surfactant fluorescence and causes the development of diffuse vesicular emphysema. On the first day of adaptation atelectatic foci dominate over emphysema, and the pulmonary structure normalizes afterwards. During de-adaptation, surface activity and cellular surfactant fluorescence are higher than the control levels. Surface activity and extracellular surfactant fluorescence recover steadily by the fifth day of adaptation. The amount of phagocytized surfactant in alveolar macrophages is increased, with the changes being opposite to those characteristic of extracellular surfactant.     

Acoustic evidence of airway opening during recruitment in excised dog lungs.

The aim of this study was to test the hypothesis that the mechanism of recruitment and the lower knee of the pressure-volume curve in the normal lung are primarily determined by airway reopenings via avalanches rather than simple alveolar recruitments. In isolated dog lung lobes, the pressure-volume loops were measured, and crackle sounds were recorded intrabronchially during both the first inflation from the collapsed state to total lobe capacity and a second inflation without prior degassing. The inflation flow contained transients that were accompanied by a series of crackles. Discrete volume increments were estimated from the flow transients, and the energy levels of the corresponding crackles were calculated from the sound recordings. Crackles were concentrated in the early phase of inflation, with the cumulative energy exceeding 90% of its final value by the lower knee of the pressure-volume curve. The values of volume increments were correlated with crackle energy during the flow transient for both the first and the second inflations (r(2) = 0.29-0.73 and 0.68-0.82, respectively). Because the distribution of volume increments followed a power law, the correlation between crackle energy and discrete volume increments suggests that an avalanche-like airway opening process governs the recruitment of collapsed normal lungs.     

Cyclic nucleotides (cAMP and cGMP) in the dog plasma during extracorporeal hemocarboperfusion

The concentrations of cyclic nucleotides (cAMP and cGMP) were measured in blood plasma of dogs subjected to extracorporeal hemocarboperfusion. In spite of complete and irreversible absorption of cyclic nucleotides by the coal absorbent, SKN-2M, the concentration of cGMP in plasma remained within normal. The concentration of cAMP increased 1.5-2.5-fold. The rise in the cAMP concentration was not connected with injection of sodium thiopental and heparin before hemocarboperfusion. It is assumed that cyclic nucleotides play the role of circulating intercellular regulators in blood plasma. These regulators are necessary for the normal course of metabolic processes.     

Protection of the blood-brain barrier during acute and chronic hypertension

A new concept about sympathetic nerves has emerged recently: not only is sympathetic tone important in short-term regulation of vascular resistance, but chronic effects of nerves on vessels have important effects. This concept is supported by studies of mechanisms by which sympathetic nerves protect the blood-brain barrier (BBB). The BBB is susceptible to disruption during acute and chronic hypertension. Acute, severe hypertension produces passive dilatation of cerebral vessels with disruption of the BBB. Sympathetic stimulation attenuates the increase in cerebral blood flow during acute hypertension and thereby protects the BBB. During chronic hypertension, we have observed disruption of the barrier, which may contribute to hypertensive encephalopathy. Sympathetic nerves protect against disruption of the BBB during chronic hypertension. This protective effect is apparently related to a trophic effect of nerves in promotion of cerebral vascular hypertrophy during chronic hypertension. Thus, this is the first evidence that, in the same vascular bed, sympathetic nerves have two different protective effects. Protection of the BBB is accomplished acutely by sympathetic neural effects on vascular resistance and chronically by promotion of vascular hypertrophy.     

Ultrastructure of celiac plexus nodes in the dog

A normal structure of the celiac plexus nodes has been studied in 12 mature dogs. As demonstrate the results of the investigation, gangliocytes of the celiac plexus are characterized with a well developed granular cytoplasmic reticulum and a large number of Golgi complexes. In perikaryon of the gangliocytes, an essential number of mitochondria, microtubules, free ribosomes and polysomes, lysosomes, multivesicular bodies, agranular and granular vesicles and neurofilaments are found. The gangliocyte has one nucleus which occupies about 1/3 of the whole area of the cell. The nucleus is rich in chromatin. The nucleolus makes about 1/5 of the whole area of the nucleus and is intensively rich in heterochromatin. In the celiac plexus nodes amyelinated neural fibers predominate. Dendrites in the gangliocytes differ from axons by a higher electron density of their matrix and contain the same organells that does the perikaryon of the gangliocyte. Rather complex glyoneuronal interrelations are observed in the canine celiac plexus nodes. Synapses are revealed in all ganglionar zones. The axodendritic synaptic contacts predominate over the axosomatic ones.