The (in-)validity of volatile POCT parameters from patients beyond normothermia.

BACKGROUND: A common characteristic of all blood gas analyzers on the market is that measurements are processed at 37°C, not at the real patients´ temperature. Subsequently temperature-sensitive parameters can be mathematically corrected (alpha-stat method) or used directly (pH-stat method). National rules in Germany (Rili-BAEK) demand defined accuracy and precision without any restriction to samples´ temperatures or corrections. As consequence in the investigation at hand we tried to find out whether blood gas analyzers can fulfill the regulations for pCO2 and pO2 when normothermia of the matrix is not given. METHODS: Five matrices (blood from intensive care unit (ICU) patients, blood from healthy donors and 3 levels of bovine based quality control material) were tonometered at "high" and "low" partial pressures of O2 and CO2 within the RiLi-BAEK controlled range at 32, 37 and 40°C. One mL material was aspired into each blood gas (BG) syringe and analysis was accomplished immediately after. The procedure was repeated 10-fold for "high" and "low" gas concentrations and run on 4 different analyzers. At 18°C instead to the "high" one a "median" gas (n=10 as well) was employed. Every condition which constitutes of temperature (4), matrix (5), analyzer (4) and level of the partial pressure (2) led to a total of 1600 measurements. RESULTS: At 32°C or 37°C matrix temperature 7.5% to 27.5% of the pCO2(T) and between 14.5% and 28.1% of the pO2(T) results were outside the borders required by the RiLi-BAEK. At 18°C or 40°C the number of results beyond the allowed borders grows up to 82.5% for pCO2(T) and 73% for pO2(T) depending on the partial pressure (PP) level. CONCLUSIONS: High precision in automated quality control (at a constant matrix temperature) is given in modern BGAnalyzers but is counteracted in practice by non normothermic patient's temperature and unavoidable sample handling effects.

Preanalytics: The (in-)stability of volatile POCT parameters and the homogeneity of blood in syringes at the market.

BACKGROUND: In between calibrations, quality controls and so on reduce the availability of blood gas analyzers. Despite the intended urgency of the measurements, these inhibitory circumstances cause delays of measurements. The comparison of changes (primarily PO2 and PCO2, secondarily ctHb) in syringes from different suppliers and the embedding into guideline ranges are the objectives of this study. METHODS: Five matrices were tonometered at two levels within the German guideline (RiLi-BAEK) controlled range. Matrices were aspired into each syringe and blood gas analysis accomplished after 0 to 30min. The procedure was repeated 5 to 8-fold for the gas concentrations and every condition which consisted of syringe type (7), matrices (5) and time delay (7). RESULTS: Syringes produce almost identical effects on partial pressures during the 30min observation period. Initial fast changes arise when partial pressure (PP) differs widely from the atmospheric pressure and are followed by diffusion, gas production or consumption and ctHb depending effects. CONCLUSIONS: Only normal arterial blood gases without "atmospheric pollution" are not affected by the syringe materials within 30min. The homogeneity of a de-aerated and capped ICU-patients' sample is hardly to be provided after more than 10min of resting without mechanical assistance.

Analysis of metabolic alterations in Arabidopsis following changes in the carbon dioxide and oxygen partial pressures.

As sessile organisms, plants are subject to a multitude of environmental variations including several which directly affect their interaction with the atmosphere. Given the indiscriminant nature of Rubisco, the relative rates of photosynthesis and photorespiration are known to be responsive to changes in gas composition. However, comprehensive profiling methods have not yet been applied in order to characterize the wider consequences of these changes on primary metabolism in general. Moreover, although transcriptional profiling has revealed that a subset of photorespiratory enzymes are co-expressed, whether transcriptional responses play a role in short-term responses to atmospheric compositional changes remains unknown. To address these questions, plants Arabidopsis thaliana (Arabidopsis) ecotype Columbia (Col-O) grown under normal air conditions were transferred to different CO2 and O2 concentrations and characterized at the physiological, molecular, and metabolic levels following this transition. The results reveal alterations in the components, which are directly involved in, or supporting, photorespiration, including transcripts and metabolite levels. The results further highlight that the majority of the regulation of these pathways is not mediated at the level of transcription and that the photorespiratory pathway is essential also in conditions in which flux through the pathway is minimized, yet suggest that flux through this pathway is not mediated at the level of transcription.

Safety of poly (ethylene glycol)-coated perfluorodecalin-filled poly (lactide-co-glycolide) microcapsules following intravenous administration of high amounts in rats.

The host response against foreign materials designates the biocompatibility of intravenously administered microcapsules and thus, widely affects their potential for subsequent clinical use as artificial oxygen/drug carriers. Therefore, body distribution and systemic parameters, as well as markers of inflammation and indicators of organ damage were carefully evaluated after administration of short-chained poly (vinyl alcohol, (PVA)) solution or poly (ethylene glycol (PEG))-shielded perfluorodecalin-filled poly (d,l-lactide-co-glycolide, PFD-filled PLGA) microcapsules into Wistar rats. Whereas PVA infusion was well tolerated, all animals survived the selected dose of 1247 mg microcapsules/kg body weight but showed marked toxicity (increased enzyme activities, rising pro-inflammatory cytokines and complement factors) and developed a mild metabolic acidosis. The observed hypotension emerging immediately after start of capsule infusion was transient and mean arterial blood pressure restored to baseline within 70 min. Microcapsules accumulated in spleen and liver (but not in other organs) and partly occluded hepatic microcirculation reducing sinusoidal perfusion rate by about 20%. Intravenous infusion of high amounts of PFD-filled PLGA microcapsules was tolerated temporarily but associated with severe side effects such as hypotension and organ damage. Short-chained PVA displays excellent biocompatibility and thus, can be utilized as emulsifier for the preparation of drug carriers designed for intravenous use.

Lower hypoxia thresholds of cuttlefish early life stages living in a warm acidified ocean.

The combined effects of future ocean acidification and global warming on the hypoxia thresholds of marine biota are, to date, poorly known. Here, we show that the future warming and acidification scenario led to shorter embryonic periods, lower survival rates and the enhancement of premature hatching in the cuttlefish Sepia officinalis. Routine metabolic rates increased during the embryonic period, but environmental hypercapnia significantly depressed pre-hatchling's energy expenditures rates (independently of temperature). During embryogenesis, there was also a significant rise in the carbon dioxide partial pressure in the perivitelline fluid (PVF), bicarbonate levels, as well as a drop in pH and oxygen partial pressure (pO2). The critical partial pressure (i.e. hypoxic threshold) of the pre-hatchlings was significantly higher than the PVF oxygen partial pressure at the warmer and hypercapnic condition. Thus, the record of oxygen tensions below critical pO2 in such climate scenario indicates that the already harsh conditions inside the egg capsules are expected to be magnified in the years to come, especially in populations at the border of their thermal envelope. Such a scenario promotes untimely hatching and smaller post-hatching body sizes, thus challenging the survival and fitness of early life stages.

Spinal 5-HT7 receptors and protein kinase A constrain intermittent hypoxia-induced phrenic long-term facilitation.

Phrenic long-term facilitation (pLTF) is a form of serotonin-dependent respiratory plasticity induced by acute intermittent hypoxia (AIH). pLTF requires spinal Gq protein-coupled serotonin-2 receptor (5-HT2) activation, new synthesis of brain-derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, TrkB. Intrathecal injections of selective agonists for Gs protein-coupled receptors (adenosine 2A and serotonin-7; 5-HT7) also induce long-lasting phrenic motor facilitation via TrkB "trans-activation." Since serotonin released near phrenic motor neurons may activate multiple serotonin receptor subtypes, we tested the hypothesis that 5-HT7 receptor activation contributes to AIH-induced pLTF. A selective 5-HT7 receptor antagonist (SB-269970, 5mM, 12 µl) was administered intrathecally at C4 to anesthetized, vagotomized and ventilated rats prior to AIH (3, 5-min episodes, 11% O2). Contrary to predictions, pLTF was greater in SB-269970 treated versus control rats (80 ± 11% versus 45 ± 6% 60 min post-AIH; p<0.05). Hypoglossal LTF was unaffected by spinal 5-HT7 receptor inhibition, suggesting that drug effects were localized to the spinal cord. Since 5-HT7 receptors are coupled to protein kinase A (PKA), we tested the hypothesis that PKA inhibits AIH-induced pLTF. Similar to 5-HT7 receptor inhibition, spinal PKA inhibition (KT-5720, 100 µM, 15 µl) enhanced pLTF (99 ± 15% 60 min post-AIH; p<0.05). Conversely, PKA activation (8-br-cAMP, 100 µM, 15 µl) blunted pLTF versus control rats (16 ± 5% versus 45 ± 6% 60 min post-AIH; p<0.05). These findings suggest a novel mechanism whereby spinal Gs protein-coupled 5-HT7 receptors constrain AIH-induced pLTF via PKA activity.