Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476273 (respiratory distress)
19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beneficial effects of supplemental oxygen delivered to patients suffering from acute respiratory distress is offset by its reduction to genotoxic reactive oxygen species (ROS) that inhibit proliferation and kill pulmonary cells. Cells respond to oxygen-induced damage by expressing the tumor suppressor p53 and the cyclin-dependent kinase inhibitor p21(Cip1/WAF1/Sdi1) (p21), which limits proliferation by blocking entry into S phase. Since preventing DNA synthesis during genotoxic stress may enhance survival, the current study examines whether hyperoxia induces p21 through a p53-dependent pathway and whether p21 protects cells from the toxic effects of oxygen. HCT116 colon carcinoma cells and clonal lines lacking p53 or p21were used in this study because they allow direct cytotoxic comparisons between isogenic cells, without complications arising from unknown genetic differences between nonhomologous cell lines. Hyperoxia (95% O2, 5% CO2) increased p53 abundance, phosphorylation of p53 on serine 15, and p21 mRNA and protein in parental HCT116 cells that ceased proliferation. In contrast, p21 was not detected in either p53- or p21-deficient HCT116 cells, which exited the G1 compartment and were arrested in S and G2/M phases during hyperoxia. Trypan blue-dye exclusion revealed that induction of p21 markedly enhanced survival during exposure and colony survival assays showed that p21 enhanced the ability to resume proliferation during recovery in room air. The observation that p53-dependent induction of p21 prevents exit from G1 and promotes survival during hyperoxia is consistent with the importance of limiting DNA replication during genotoxic stress caused by oxygen exposure.
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PMID:p53-dependent induction of p21(Cip1/WAF1/Sdi1) protects against oxygen-induced toxicity. 1156 65

The purpose of this study was to compare low-dose (LD) and high-dose (HD) systemic heparinization in a prospective randomized study of arteriovenous carbon dioxide removal (AVCO2R) during acute respiratory distress syndrome, using a commercially available heparin-coated oxygenator. Adult sheep (n = 13) received an LD50 smoke inhalation and 40% TBSA third degree cutaneous flame burn injury. At 40-48 h post-injury, animals underwent cannulation of the carotid artery and jugular vein and were then randomized to HD heparin (activated clotting time, ACT > 300s, n = 6) and LD heparin (ACT < 200s, n =7) and placed on AVCO2R for approximately 72 h using an oxygenator with the Trillium Bio-Passive Surface. Mean ACTs were significantly different, as expected (HD: 446 +/- 26s, LD: 213 +/- 12s, p < 0.05). AVCO2R shunt flow averaged approximately 13% of cardiac output with mean CO2 removal similar in HD and LD, p = NS. The hematocrit, platelet count, and fibrin degradation products for the two groups were not different. No differences in thrombosis or bleeding were noted. In conclusion, LD systemic heparin (ACT < 200s) with a heparin-coated oxygenator does not increase thrombogenicity during AVCO2R for smoke/burn-induced severe lung injury in sheep.
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PMID:Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal. 1176 Oct 85

Increased understanding of the mechanisms and effects of acute respiratory failure has not been accompanied by more precise criteria by which the clinician can determine when intubation should be carried out and invasive positive-pressure ventilation (IPPV) instituted in a given patient. The indications traditionally offered in reviews and textbooks have tended to be either so broad as not to be very helpful in an individual case, or of questionable clinical relevance and too cumbersome for practical use. This review updates the indications for IPPV in adult patients with acute respiratory failure by examining available evidence from clinical trials and by considering new management alternatives that have become available in the last 20 years. Indications for IPPV based on specific threshold values for P(CO2) and pH or on various indices of arterial oxygenation have generally not been validated by clinical evidence, and it is unlikely that any cutoff value would be applicable to all patients or all categories of acute respiratory failure. Stated another way, there is probably no single value for arterial P(CO2), pH, or P(O2) that by itself constitutes an indication for IPPV. Compelling face validity justifies the use of IPPV in cases of apnea or when it appears certain that respiratory arrest is about to occur. However, dyspnea, tachypnea, or the subjective impression of respiratory distress are probably not in themselves justification for emergency intubation. It should be possible to avoid IPPV and its attendant complications in many cases of acute hypercapnic respiratory failure. In acute exacerbations of chronic obstructive pulmonary disease, noninvasive positive-pressure ventilation (NPPV) should be the initial ventilation approach unless the patient has one of several specific exclusion criteria such as cardiovascular instability or severely impaired mental status. It may also be possible to avoid intubation through the use of NPPV in certain immunocompromised patients with early acute hypoxemic respiratory failure. However, in other settings of acute hypoxemic respiratory failure, such as acute lung injury and acute respiratory distress syndrome, this has not been shown. The use of IPPV may improve outcomes in patients with severe cardiogenic shock. However, IPPV has not proven to be beneficial in traumatic brain injury and flail chest, in the absence of other indications.
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PMID:Indications for mechanical ventilation in adults with acute respiratory failure. 1187 5

Alveolar (and thus arterial) P(O2) and P(CO2) clearly depend on minute ventilation. However, we need to balance gas exchange goals against the risk of overstretching, especially of the healthier regions of the lung. The plateau pressure is probably the best easily-obtained marker of the risk of stretch in the lung, and a commonly quoted threshold is 30--35 cm H(2)O, the normal maximum transalveolar pressure at total lung capacity. In establishing the proper balance of stretch versus gas exchange, we need to address what levels of pH and P(aO2) we consider acceptable. There are no good data to guide us on the lowest tolerable pH, but 7.2 is commonly quoted in the literature, and 7.15 was the lower limit of acceptability in the ARDS (acute respiratory distress syndrome) Network trial. P(O2) levels as low as 55 mm Hg may be well tolerated, provided there is reasonable oxygen delivery. In distributing the desired minute volume between respiratory frequency and tidal volume (V(T)), a V(T) of 6 mL/kg ideal body weight has been shown to improve ARDS outcome, compared to 12 mL/kg. Thus, 6 mL/kg should be the "start point." Adjustments upward could be considered the plateau pressure is acceptable, in order to improve gas exchange or comfort. Conversely, downward adjustments should be considered if the plateau pressure is high and the gas exchange is acceptable. Frequency is adjusted for the desired minute ventilation. It must be recognized, however, that as frequency (and minute ventilation) increases, the risk of air trapping and intrinsic positive end-expiratory pressure (PEEP) increases. Just like applied PEEP, intrinsic PEEP increases the baseline pressure and stretch upon which the V(T) is delivered. The end-inspiratory stretch increases accordingly. The shape and duration of the flow pattern may affect gas mixing, recruitment, cardiac function, intrinsic PEEP buildup, and patient comfort. It is also conceivable that certain flow patterns can produce an acceleration injury. Although small clinical trials using physiologic end points espouse certain flow patterns, there are no good outcome data at present supporting any particular approach. Some authors suggest that high-frequency ventilation (HFV) might be considered an "ultimate" lung-protective strategy. HFV creates considerable intrinsic PEEP, which, when coupled with sustained inflation maneuvers, can provide substantial alveolar recruitment. In addition, the small V(T) of HFV prevents excessive end-inspiratory distention. Although considerable clinical data support the use of HFV in pediatric patients at risk for ventilator-induced lung injury, there are few data from adults. Whether HFV will prove valuable in well-designed open lung strategies in the adult population still has to be determined.
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PMID:Setting the frequency-tidal volume pattern. 1187 6

Percutaneous arteriovenous CO2 removal (AVCO2R) uses a simple arteriovenous (A-V) shunt for near-total CO2 removal that allows significant reductions in minute ventilation. We critically reviewed our algorithm-directed perioperative anesthesia management in our LD40 ovine smoke-burn injury model of acute respiratory distress syndrome (ARDS) treated with AVCO2R. General anesthesia is required for: (1) Vascular access followed by ARDS model development by smoke insufflation (36 breaths) plus 40% TBSA III degrees burn with mechanical ventilation. Induction: 12.5 mg/kg im ketamine and 4% halothane by mask, then intubation. Maintenance: 1.0-2.5% halothane in 100% O2; (2) When PaO2/FiO2 < 200 (48-52 h), sheep randomized to the AVCO2R (n = 8) or SHAM (n = 8) procedure. Induction: 66% N2O and 5% isoflurane in balance O2. Maintenance: 1.5-2.5% isoflurane in 100% O2 for AVCO2R, cannulation (10F carotid artery, 14F jugular vein); (3) Postop, both groups had algorithm-directed ventilator management, identical heparin (ACT > 300 s), fluid, and analgesia management. All sheep met criteria for ARDS, survived anesthesia, and were standing by 0.5-5 h. There were no complications attributable to anesthesia. The absence of anesthesia-related complications allows model development for outcomes studies for ARDS in general and AVCO2R specifically.
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PMID:Arterio-venous CO2 removal (AVCO2R) perioperative management: rapid recovery and enhanced survival. 1193 89

Airborne particulate matter (PM) is an important environmental issue because of its association with acute respiratory distress in humans, although the specific particle characteristics that cause lung damage have yet to be identified. Particle size, acid aerosols, water-soluble transition metals (e.g. Cu, Fe, V, Ni and Zn), polyaromatic hydrocarbons, and particle composition are the focus of several popular hypotheses addressing respiratory distress. All of the above mentioned characteristics are contained in PM generated from the combustion of both pulverized coal, and biomass, including dried municipal sewage sludge (MSS). In this investigation, we report results from collaborative interdisciplinary research on the inhalation health risks caused by particles emitted from the co-combustion of municipal sewage sludge (MSS) and coal. A solid particle resuspension system was implemented to resuspend ash particles. Mice were exposed to resuspended coal and MSS/coal ash particles. Mice exposed to MSS/coal ash particulate demonstrated significant increases in lung permeability, a marker of the early stages of pathological lung injury, while the mice exposed to coal-only ash did not. These results show that the composition of particles actually inhaled is important in determining lung damage. Zinc was significantly more concentrated in the MSS/coal ash than coal ash particles and the pH of these particles did not differ significantly. Specifically, an MSS/coal mixture, when burned, emits particles that may cause significantly more lung damage than coal alone, and that consequently, the use of MSS as a 'green', CO2-neutral replacement fuel should be carefully considered.
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PMID:Resuspension of coal and coal/municipal sewage sludge combustion generated fine particles for inhalation health effects studies. 1199 68

The aim of this paper was the registration of the answers of the smooth musculature of the trachea at the different concentrations of ethanol, at the gestationary weeks of the newborns with the respiratory distress syndrome. In vitro examination was worked at the nonhuman preparations of the trachea of the newborns at autopsy material, the same material of the trachea and the lungs is fixed on 10% puferized formaline for the pathomorphologic examinations (RDS). The incubation of the preparation is performed on the water bath with Kreps solution, with the constant aerozation (O2 95% and CO2 5%). The answers are registered by means of the Transducer Statham UC2 at higher canal written physiography Watanabe HSE 6600. The preparations are treated with various concentrations of ethanol 96% (0.2 ml, 0.5 ml and 1.0 ml). From the received results we came to the conclusion that the effect of ethanol in the various concentrations at the smooth musculature of the trachea in the newborns with RDS, is demonstrated the contractile or the relaxing effect without statistic significance in various gestational weeks (p > 0.05).
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PMID:[An in vitro study of tracheal smooth muscle response to ethanol in neonates with respiratory distress syndrome]. 1237 55

Arteriovenous carbon dioxide removal (AVCO2R) as an alternative treatment for acute respiratory distress syndrome uses a low resistance gas exchanger in a simple arteriovenous shunt to achieve total CO2 removal and allow lung rest. We have previously shown in our clinically relevant LD40 ovine model of smoke/burn induced acute respiratory distress syndrome that AVCO2R allows significant decreases in respiratory rate, tidal volume, peak airway pressure, and FiO2, as compared with standard mechanical ventilation. In addition, we have shown in a prospective randomized outcomes study that AVCO2R increases ventilator free days, decreases ventilator dependent days, and significantly improves survival. The purpose of this study is to further define the limits of AVCO2R through hemodynamic augmentation and evaluation of peak end expiratory pressure (PEEP). Administration of an alpha agonist (phenylephrine) and a beta agonist (isoproterenol) increased mean arterial pressure (MAP) and cardiac output (CO), respectively. MAP increases ranged from 2.4% to 94.4% and CO increases ranged from 33% to 146%. Phenylephrine caused elevations in MAP (2.4-94.4%) and AVCO2R flow (9-67%), and CO never decreased more than 10%. Isoproterenol administration increased CO (33-146%), decreased MAP (9-54%), and decreased AVCO2R flow (11-42%). In a second group, PEEP was increased stepwise from 0 (baseline) to 20 cm H2O. Increasing PEEP did not result in significant hemodynamic changes (< 10% change from baseline PEEP) for MAP, CO, or AVCO2R flow. In conclusion, alpha agonist administration increased AVCO2R blood flow, whereas beta agonist administration decreased MAP and AVCO2R blood flow, despite CO elevation. Various levels of PEEP are well tolerated and thus allow a range of options during AVCO2R.
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PMID:The effect of augmented hemodynamics on blood flow during arteriovenous carbon dioxide removal. 1255 4

In most severe cases of the acute respiratory distress syndrome, veno-venous extracorporeal membrane oxygenation (ECMO) can be used to facilitate gas exchange. However, the clinical use is limited due to the size and the concomitant risk of severe adverse events of conventionally-used centrifugal blood pumps with high extracorporeal blood volumes. The DeltaStream blood pump is a small-sized rotary blood pump that may reduce extracorporeal blood volume, foreign surfaces, contact activation of the coagulation system, and blood trauma. The aim of the present study was to test the safety and efficacy of the DeltaStream pump for ECMO in animals with normal lung function and experimental acute lung injury (ALI). Therefore, veno-venous ECMO was performed for 6 hours in mechanically ventilated pigs with normal lung function (n=6) and with ALI induced by repeated lung lavage (n=6) with a blood flow of 30% of the cardiac output. Gas flow with a FiO2 of 1.0 was set to equal blood flow. With a mean activated clotting time of 121 +/- 22 s, no circulatory impairment or thrombus formation was revealed during ECMO. Furthermore, free plasma Hb did not increase. In controls, hemodynamics and gas exchange remained unchanged. In animals with ALI, hemodynamics remained stable and gas transfer across the extracorporeal oxygenators was optimal, but only in 2 animals was a marked increase in PaO2 observed. CO2 removal was efficacious in all animals. We concluded that the DeltaStream blood pump may be used for veno-venous ECMO without major blood damage or hemodynamic impairment.
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PMID:Extracorporeal gas exchange with the DeltaStream rotary blood pump in experimental lung injury. 1278 May 7

Conventional gas ventilation is often unsuccessful for premature neonatal patients suffering from respiratory distress syndrome (RDS). For such patients, liquid ventilation (LV) with perfluorocarbon (PFC) liquids has been proposed. By eliminating the air-liquid interface in saccules (the premature gas exchange structures), where scarce or absent surfactant production exists, pulmonary instability is avoided, lung compliance is improved, and atelectatic saccules are recruited, ultimately lowering the saccular pressure. Tidal LV involves administrating a liquid tidal volume to the patient at each respiratory cycle, and therefore requires a dedicated circuital setup to deliver, withdraw, and refresh the PFC during the treatment. We have developed a prototype liquid breathing system (LBS). The apparatus comprises two subcircuits managed by a personal computer based control system. The ventilation subcircuit performs inspiration/expiration with two sets of peristaltic pumps. A system to evaluate the true inspired/expired volumes was devised that consists of two reservoirs equipped with pressure transducers measuring the hydraulic head of the fluid therein. Volume accuracy was +/- 0.3 ml. The refresh subcircuit properly processes the PFC by performing filtration (DFA, Pall, NY), oxygenation, CO2 scavenge, and heat exchange (SciMed 2500, Life Systems, MN). The new apparatus has been used in preliminary animal tests on five newborn mini pigs with induced acquired RDS. The PFC used was RM-101 (Miteni, Milano, Italy). The animals were successfully supported for 4 hours each. Mean arterial O2 pressure was 131.4 mm Hg (range 79.0-184.2), and mean arterial CO2 pressure was 64.8 mm Hg (range 60.0-73.4).
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PMID:Volume controlled apparatus for neonatal tidal liquid ventilation. 1279 Mar 72


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