300 LACK OF DRUG EFFECT ON OXYGEN INDUCED RETINAL ARTERY CONSTRICTION IN THE KITTEN

Hypotension and hypoxemia worsen traumatic brain injury outcomes. Hyperoxic resuscitation is controversial. The authors proposed that hyperoxia would improve hemodynamics and neuronal survival by augmenting oxygen delivery despite increased oxidative stress and neuroinflammation in experimental combined controlled cortical impact plus hemorrhagic shock in mice. Adult C57BL6 mice received controlled cortical impact followed by 35 min of hemorrhagic shock (mean arterial pressure, 25-27 mmHg). The resuscitation phase consisted of lactated Ringer's boluses titrated to mean arterial pressure greater than 70 mmHg. Definitive care included returning shed blood. Either oxygen or room air was administered during the resuscitation phases. Brain tissue levels of oxidative stress and inflammatory markers were measured at 24 h and hippocampal neuronal survival was quantified at 7 days. Hyperoxia markedly increased brain tissue oxygen tension approximately four- to fivefold (n = 8) and reduced resuscitation fluid requirements approximately 15% (n = 53; both P < 0.05). Systemic and cerebral physiologic variables were not significantly affected by hyperoxia. Hippocampal neuron survival was approximately 40% greater with oxygen versus room air (n = 18, P = 0.03). However, ascorbate depletion doubled with oxygen versus room air (n = 11, P < 0.05). Brain tissue cytokines and chemokines were increased approximately 2- to 20-fold (n = 10) after combined controlled cortical impact injury plus hemorrhagic shock, whereas hyperoxia shifted cytokines toward a proinflammatory profile. Hyperoxic resuscitation of cortical impact plus hemorrhagic shock reduced fluid requirements and increased brain tissue oxygen tension and hippocampal neuronal survival but exacerbated ascorbate depletion and neuroinflammation. The benefits of enhanced oxygen delivery during resuscitation of traumatic brain injury may outweigh detrimental increases in oxidative stress and neuroinflammation.

The American Heart Association recommends tidal volumes of 700 to 1000 mL during mouth-to-mouth ventilation, but smaller tidal volumes of 500 mL may be of advantage to decrease the likelihood of stomach inflation. Because mouth-to-mouth ventilation gas contains only 17% oxygen, but 4% carbon dioxide, it is unknown whether 500-mL tidal volumes given during rescue breathing may result in insufficient oxygenation and inadequate carbon dioxide elimination. In a university hospital research laboratory, 20 fully conscious volunteer health care professionals were randomly assigned to breathe tidal volumes of 500 or 1000 mL of mouth-to-mouth ventilation gas (17% oxygen, 4% carbon dioxide, 79% nitrogen), or room air control (21% oxygen, 79% nitrogen) for 5 min. Arterial blood gases were taken immediately before, and after breathing 5 min of the experimental gas composition. When comparing 500 versus 1000 mL of mouth-to-mouth ventilation tidal volumes with 500 mL of room air, 500 mL of mouth-to-mouth ventilation tidal volume resulted in significantly (P < 0.05) lower mean +/- SEM arterial oxygen partial pressure (70 +/- 1 versus 85 +/- 2 versus 92 +/- 3 mm Hg, respectively), and lower oxygen saturation (94 +/- 0.4 versus 97 +/- 0.2 versus 98 +/- 0.2%), but increased arterial carbon dioxide partial pressure (46 +/- 1 versus 40 +/- 1 versus 39 +/- 1 mm Hg, respectively). Sixteen of 20 volunteers had to be excluded from the experiment with 500 mL of mouth-to-mouth ventilation gas after about 3 min instead of after 5 minutes as planned because of severe nervousness, sweating, and air hunger. We conclude that during simulated mouth-to-mouth ventilation, only large (approximately 1000 mL), but not small (approximately 500 mL) tidal volumes were able to maintain both sufficient oxygenation and adequate carbon dioxide elimination. To provide efficient mouth-to-mouth ventilation, it is important to administer tidal volumes of 1000 mL; tidal volumes of 500 mL were not adequate.

Combining carbon dioxide and strong emulsifier in-depth huff and puff with DCA microsphere plugging in horizontal wells of high-temperature and high-salinity reservoirs

Our previous work demonstrated that hypoxia decreases transcription of the human prostaglandin H synthase-2 (PGHS-2) gene during exposure to lipopolysaccharide (LPS), resulting in decreased prostaglandin E2 (PGE2) synthesis (J. Biol. Chem. 269:32979-32984, 1994). Because PGE2 is reported to inhibit interleukin 1 (IL-1) and tumor necrosis factor (TNF), it is likely that hypoxia, through changes in PGE2, will alter IL-1 and TNF release from the human alveolar macrophage. In addition, like PGHS-2, the TNF and IL-1 promoters contain oxidant-sensitive elements which might be altered by hypoxia. Therefore, we hypothesized that LPS-induced release of TNF and IL-1 would be altered by hypoxia. To test this, human alveolar macrophages were cultured for 24 h with 0 to 1 microgram/ml LPS in a room-air incubator with 5% CO2 or a hypoxia incubator continuously perfused with 5% CO2/95% N2 (O2 < 0.05%). With room air, LPS increased IL-1 beta mRNA and increased IL-1 beta protein release into the culture medium in a dose-dependent manner. Hypoxia increased the LPS-stimulated release of IL-1 beta 30% above that of room-air controls. However, immunoblots showed that hypoxia caused no change in intracellular IL-1 beta compared with room-air controls. There was also no change in LPS-induced IL-1 beta message with hypoxia. The inhibitor of IL-1, IL-1RA, was apparently decreased by hypoxia, but this decrease was not statistically significant. TNF-alpha mRNA and release of protein also increased during LPS exposure in room air. Hypoxia markedly increased LPS-induced TNF-alpha message and release of TNF-alpha compared with LPS-exposed room-air controls. Consistent with our prior observations, hypoxia decreased LPS-induced PGHS-2 message and protein, and also the PGHS-2 product, PGE2. Because PGE2 is reported to inhibit the expression of IL-1 and TNF genes, we inhibited PGE2 synthesis with indomethacin during culture in room air; the result was an increase in the release of IL-1 and TNF. In additional studies, adding PGE2 inhibited TNF release from the hypoxia cells to values near those of room-air controls. In summary, hypoxia increases the release of the cytokines IL-1 beta and TNF-alpha. This increase may be due to decreased PGE2 synthesis during hypoxia. These results demonstrate that the response of the human alveolar macrophage to hypoxia is complex. Hypoxia increases the LPS-stimulated release of the inflammatory cytokines IL-1 and TNF, whereas synthesis of PGHS-2, which generates the anti-inflammatory prostaglandin PGE2 is decreased.

A total of ten 6-month-old male rhesus monkey (Macaca mulatta) infants, born full-term, were positive-pressure ventilated with greater than 95% oxygen or room air (controls). A protocol was used which closely simulated pediatric intensive care. To test if regulatory peptides were affected by the oxygen treatment, and to search for an early marker of oxygen toxicity, lung tissue samples and systemic mixed venous blood were collected at 6, 12 and 24 hours after onset of treatment. The peptides, gastrin releasing peptide (GRP), calcitonin gene-related peptide (CGRP), peptide YY (PYY), vasoactive intestinal peptide (VIP) and somatostatin (SOM), were quantitated in lung tissue extracts and plasma using radioimmunoassay. Lung tissue GRP, CGRP, and PYY levels appeared to decrease gradually with time, perhaps as a result of the positive pressure ventilation procedure. GRP and CGRP levels decreased less among monkey infants ventilated with oxygen, thus they were significantly higher at 24 hours than in air ventilated controls. VIP levels were significantly lower among tests compared to controls at that time. Blood peptide levels did not change with oxygen treatment. These results suggest that tissue concentrations of certain pulmonary regulatory peptides can become altered by ventilation with greater than 95% oxygen. A blood borne peptide marker was not identified.

Further studies on the controlled atmosphere storage of avocados

To study therapeutic effects by using different oxygen therapies in rats with acute carbon dioxide poisoning, to select the best oxygen therapy technology for patients with acute carbon dioxide poisoning on the spot. Sixty healthy male Sprague-Dawley rats were randomized into normal control group, carbon dioxide exposure group, hyperbaric oxygen treatment group (pressure 2 ATA, FiO(2)100%), high concentration of atmospheric oxygen treatment group (FiO(2)50%), low concentration of atmospheric oxygen treatment group (FiO(2)33%). After treated with different oxygen in rats with acute carbon dioxide poisoning, arterial pH, PO2 and PCO2 of rats were detected, in addition observe pathological changes of lung tissue and brain tissue. The arterial pH (7.31 ± 0.06) and PO2 [(68.50 ± 15.02) mm Hg] of carbon dioxide exposure group were lower than those of control group [pH (7.42 ± 0.02) and PO2 (92.83 ± 8.27) mm Hg], PCO2 [(71.66 ± 12.10) mm Hg] was higher than that of control group [(48.25 ± 2.59) mm Hg] (P < 0.05); the arterial pH (hyperbaric oxygen treatment group 7.37 ± 0.02, high concentration of atmospheric oxygen treatment group 7.39 ± 0.03, low concentration of atmospheric oxygen treatment group 7.38 ± 0.02) and PO2 of oxygen treatment groups [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (82.25 ± 12.98), (84.75 ± 11.24), (83.75 ± 16.77) mm Hg, respectively] were higher than that of carbon dioxide exposure group, PCO2 [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (52.25 ± 4.95), (51.75 ± 4.82), (52.66 ± 5.61) mm Hg, respectively] was lower than that of carbon dioxide exposure group (P < 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 between oxygen treatment groups and control group (P > 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 among oxygen treatment groups (P > 0.05). There was large area of bleeding of lungs in rats with carbon dioxide poisoning, the bleeding of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment was better than the rats with carbon dioxide poisoning, there was no abnormal appearance of lungs in rats with hyperbaric oxygen treatment. The light microscope observation showed that there were diffuse bleeding and exudation of lungs in rats with carbon dioxide poisoning, the bleeding and exudation of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment were better than the rats with carbon dioxide poisoning, there were only minor bleeding and exudation of lungs in rats with hyperbaric oxygen treatment. There was no difference of brain in anatomy and microscopy among all groups, there were no significant bleeding, edema, cell degeneration and necrosis. Lung pathology in acute carbon dioxide poisoning rats with hyperbaric oxygen treatment is better than the rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment, there is no significant difference of effect between high concentration of atmospheric oxygen treatment group and low concentration of atmospheric oxygen treatment group, however, the results of blood gas analysis and lung pathology than the exposure group improved, so qualified medical unit for hyperbaric oxygen therapy as soon as possible, hyperbaric oxygen treatment facilities in the absence of circumstances, the emergency treatment of early oxygen is also a good measure.

After completing this article, readers should be able to: 1. Define the indeterminate class of recommendations for neonatal resuscitation. 2. Describe the two areas of current investigation within the indeterminate class recommendations. 3. Describe the application of two techniques from other settings within the indeterminate class recommendations. 4. Describe the indeterminate class recommendation for which conflicting evidence is emerging. With the shift to evidence-based guidelines, the process of revising the scientific framework for neonatal resuscitation and the derivative educational efforts will become more predictable and accessible. Beginning with the International Guidelines 2000, an Indeterminate Class of recommendations appeared. These focused on areas of intense scientific research that may lead to clinically important therapies; technological developments widely adopted for use in other age groups that may find a role in neonatal resuscitation; or emerging evidence that conflicts substantially with previous data, resulting in a revision of recommendations to withdraw support of a particular therapeutic approach. The advent of changes in evidence-based guidelines carries the obligation to monitor the impact of such changes. Finally, entirely new questions and proposed guideline recommendations will be submitted to evidence evaluation in the future. Five Indeterminate Class recommendations appeared in the neonatal resuscitation portion of the International Guidelines 2000 (Table⇓ ). Cerebral hypothermia following hypoxic-ischemic insult and positive-pressure ventilation with room air represent proposals in the translational research phase, moving from animal and molecular models into clinical trials. The recommendations relating to adjunctive airway techniques, laryngeal mask airway and exhaled carbon dioxide detection, recognize the importance of these techniques in the older pediatric and adult populations, but acknowledge the significant limitations in their application to neonates. The statement regarding high-dose epinephrine reinforces the conflicting nature of evidence relating to this therapy, yet it acknowledges that available evidence is extrapolated largely from older age groups and falls short of supporting …

The purpose of the study was to evaluate the influence of hyperoxia and hypercapnia on respiration and metabolism during a steady-state exercise. Thirteen healthy subjects were examined during bicycle-ergometer rides at approximately 50% VO2max under four different breathing gas conditions: 1) room air (control); 2) 40% oxygen; 3) 3% carbon dioxide; 4) 40% oxygen and 3% carbon dioxide. Hyperoxia, with or without hypercapnia, decreased respiratory ventilation and carbon dioxide elimination significantly. On the other hand, oxygen uptake in hyperoxia was not significantly different from that of normoxia. Hypercapnia increased respiratory ventilation more than 30% compared to normocapnia, but it did not change oxygen uptake and carbon dioxide elimination significantly.

Recent studies suggest that VEGF may worsen pulmonary edema during acute lung injury (ALI), but, paradoxically, impaired VEGF signaling contributes to decreased lung growth during recovery from ALI due to neonatal hyperoxia. To examine the diverse roles of VEGF in the pathogenesis of and recovery from hyperoxia-induced ALI, we hypothesized that exogenous recombinant human VEGF (rhVEGF) treatment during early neonatal hyperoxic lung injury may increase pulmonary edema but would improve late lung structure during recovery. Sprague-Dawley rat pups were placed in a hyperoxia chamber (inspired O(2) fraction 0.9) for postnatal days 2-14. Pups were randomized to daily intramuscular injections of rhVEGF(165) (20 microg/kg) or saline (controls). On postnatal day 14, rats were placed in room air for a 7-day recovery period. At postnatal days 3, 14, and 21, rats were killed for studies, which included body weight and wet-to-dry lung weight ratio, morphometric analysis [including radial alveolar counts (RAC), mean linear intercepts (MLI), and vessel density], and lung endothelial NO synthase (eNOS) protein content by Western blot analysis. Compared with room air controls, hyperoxia increased pulmonary edema by histology and wet-to-dry lung weight ratios at postnatal day 3, which resolved by day 14. Although treatment with rhVEGF did not increase edema in control rats, rhVEGF increased wet-to-dry weight ratios in hyperoxia-exposed rats at postnatal days 3 and 14 (P < 0.01). Compared with room air controls, hyperoxia decreased RAC and increased MLI at postnatal days 14 and 21. Treatment with VEGF resulted in increased RAC by 181% and decreased MLI by 55% on postnatal day 14 in the hyperoxia group (P < 0.01). On postnatal day 21, RAC was increased by 176% and MLI was decreased by 58% in the hyperoxia group treated with VEGF. rhVEGF treatment during hyperoxia increased eNOS protein on postnatal day 3 by threefold (P < 0.05). We conclude that rhVEGF treatment during hyperoxia-induced ALI transiently increases pulmonary edema but improves lung structure during late recovery. We speculate that VEGF has diverse roles in hyperoxia-induced neonatal lung injury, contributing to lung edema during the acute stage of ALI but promoting repair of the lung during recovery.

The quality of the current evidence is very low. The effects of nitrous oxide and helium pneumoperitoneum compared with carbon dioxide pneumoperitoneum are uncertain. Evidence from one trial of small sample size suggests that room air pneumoperitoneum may decrease hospital costs in people undergoing laparoscopic abdominal surgery. The safety of nitrous oxide, helium, and room air pneumoperitoneum has yet to be established.Further trials on this topic are needed, and should compare various gases (i.e. nitrous oxide, helium, argon, nitrogen, and room air) with carbon dioxide under standard pressure pneumoperitoneum with cold gas insufflation for people with high anaesthetic risk. Future trials should include outcomes such as complications, serious adverse events, quality of life, and pain.

BackgroundBPD is characterized by decreased alveolarization and dysmorphic vascular growth. Although growth of the pulmonary circulation and alveolarization are closely coordinated, mechanisms that link alveolar and vascular growth are poorly...

Inhaled nitric oxide (NO) is used for the treatment of infants with pulmonary hypertension, usually in combination with high concentrations of oxygen. We hypothesized that the addition of 10 ppm NO would improve survival of neonatal mice exposed to hyperoxia. FVB mouse pups were exposed to either room air (21% O2), >95% O2, or >95% O2 plus 10 ppm NO within 24 hours of birth. At 96 hours, all room air controls, all pups exposed to room air plus 10 ppm NO, and 16 of the 30 pups exposed to >95% O2 alone survived; however, none of the 18 pups exposed to >95% O2 plus 10 ppm NO survived (p < 0.02 compared to RA or hyperoxia alone). Additional pups were exposed and the lungs were harvested at 72 hours for immunoblotting for 3-nitrotyrosine (3-NT), myeloperoxidase (MPO) and mitogen-activated protein kinase phosphatase-1 (MKP-1). There were greater 3-NT and MPO levels in the lungs from pups exposed to >95% O2 plus 10 ppm NO than from pups exposed to either >95% O2 or room air. In contrast, the addition of 10 ppm NO prevented the induction of MKP-1 due to hyperoxic exposure. Since MKP-1 is involved in the restraint of inflammatory responses, decreased MKP-1 activity may account for the greater 3-NT and MPO expression in the hyperoxia + NO exposed pups. The mortality observed when NO is combined with hyperoxia may be due, at least in part, to greater neutrophil infiltration in the lung, peroxynitrite-mediated oxidant stress and/or decreased MKP-1 expression.

Preterm birth is associated with proinflammatory conditions and alterations in adult cardiac shape and function. Neonatal exposure to high oxygen, a rat model of prematurity-related conditions, leads to cardiac remodeling, fibrosis, and dysfunction. TLR (Toll-like receptor) 4 signaling is a critical link between oxidative stress, inflammation, and the pathogenesis of cardiovascular diseases. The current study sought to investigate the role of TLR4 signaling in neonatal oxygen-induced cardiomyopathy. Male Sprague-Dawley pups were kept in 80% oxygen or room air from day 3 to 10 of life and treated with TLR4 antagonist lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides(LPS-RS) or saline. Echocardiography was performed at 4, 7, and 12 weeks. At 12 weeks, intraarterial blood pressure was measured before euthanization for histological and biochemical analyses. At day 10, cardiac TLR4, Il (interleukin) 18, and Il1β expression were increased in oxygen-exposed compared with room air controls. At 4 weeks, compared with room air-saline, saline-, but not LPS-RS treated-, oxygen-exposed animals, exhibited increased left ventricle mass index, reduced ejection fraction, and cardiac output index. Findings were similar at 7 and 12 weeks. LPS-RS did not influence echocardiography in 12 weeks room air animals. Systolic blood pressure was higher in saline- but not LPS-RS treated-oxygen-exposed animals compared with room air-saline and -LPS-RS controls. LPS-RS prevented cardiac fibrosis and cardiomyocytes hypertrophy, the increased TLR4, Myd88, and Il18 gene expression, TRIF expression, and CD68+ macrophages infiltration associated with neonatal oxygen exposure, without impact in room air rats. This study indicates that neonatal exposure to high oxygen programs TLR4 activation, which contributes to cardiac remodeling and dysfunction.

The heteromolecular insertion of carbon dioxide in combination with heterocumulenes, iso(thio)cyanates or N,N′-dicyclohexylcarbodiimide, into rhenium–alkoxy group bond was accomplished for the first time in relation to reactivity of rhenium oxoalkoxides. The ease of combined insertion of iso(thio)cyanate and carbon dioxide into Re–O(Me) bond is determined by the nature of the heterocumulene organic group. Indeed, if ethyl iso(thio)cyanate is used in the reaction, the insertion is reversible, whereas the reaction with PhNCS (unlike PhNCO) together with carbon dioxide leads to complete insertion into two Re–O(R) bonds to give the insertion product (OMe)10O6Re4[OC(O){N(Ph)C(S)}2-OMe]2. In similar reactions carried out with N,N′-dicyclohexylcarbodiimide, a dependence of the number of bonds participating in the inner-sphere condensation of the inserted moieties on the duration of the experiment was found for the first time. An increase in the time of synthesis from 3 to 5 h results in insertion involving six rather than three bonds, the heteromolecular insertion products being (OMe),O6Re4{OC(O)[(Hex)N=C=N(Hex)]2}3 and (OMe)6O6Re4{OC(O)[(Hex)N=C=N(Hex)]2}6, respectively.