Low Oxygen Areas Research Articles

Multi-factor biotopes as a method for detailed site characterization in diverse benthic megafaunal communities and habitats in deep-water off Morro Bay, California

Here we describe the methods and results for biological characterization of the benthos on a previously unexplored area of central California, USA seafloor. We conducted 40 remotely operated vehicle dives from 371 to 1173 m water depth. Seafloor habitats and megafauna (fish and invertebrates) were documented from 46.8 km of seafloor video footage. Our expanded development and analysis of biotopes from quantitative data allowed us to describe detailed biological communities, along with the physical characteristics and habitat associations within the study area. This method provides a framework for potential monitoring, detection of future environmental change (natural and anthropogenic) and comprehensive comparison to other deep water regions. From 185 h of observational video at 25 sites, nearly 120,000 annotations of organisms, habitat characters, biological detritus and anthropogenic debris were recorded and analyzed. We identified a total of 228 taxa, with 173 of them present on linear quantitative transects. Species richness for transects ranged from 0.04 to 0.28 m-2 (8–55 taxa), with densities ranging from 0.07 to 5.20 ind. m−2. Both were highest on hard substrate with greatest surface area. Densities decreased with depth. Within soft substratum zones was a large field of pockmarks, which are seafloor depressions averaging 175 m in diameter and 5 m in depth. Pockmarks have sometimes been associated with seafloor gas seepage, but here we found no biological evidence of chemosynthetic organisms. No significant differences were found in either density nor species richness at pockmark sites vs. non-pockmark sites. Mud draped greenish-black coarse sand occurred only in low oxygen areas, while hummocky, rugose mud supported somewhat different species than flat mud plains. Seventy percent of the transects occurred inside the oxygen minimum zone. We conclude that high rugosity, slope, and the presence of hard substratum were better predictors of species richness and density than oxygen concentration in this specific study. Abundant biological detritus, in the form of dead and dying pelagic pyrosomes and salps, created a large, presumably ephemeral flux of carbon to the seafloor during the study period.

High importance of coupled nitrification-denitrification for nitrogen removal in a large periodically low-oxygen estuary

The coupling between nitrification and denitrification/anammox (nitrate/nitrite used in denitrification/anammox derives from nitrification) is a significant process of reactive nitrogen (N) removal that has attracted much attention. However, the dynamics of coupled nitrification-denitrification/anammox in the periodically low-oxygen estuaries and coasts remain unclear. Here, continuous-flow experiments combined with isotope tracing techniques were conducted in periodically low-oxygen areas of the Yangtze Estuary to reveal the changes in benthic sediment denitrification and anammox as well as their coupling with nitrification. Our results showed that denitrification increased but anammox decreased during low-oxygen summer. The occurrence of low oxygen also promoted coupled nitrification-denitrification but decreased coupled nitrification-anammox. These results implied that decreased dissolved oxygen in summer did not largely restrict nitrification activity, and anaerobic denitrification/anammox regulated the magnitude of coupled nitrification-denitrification/anammox rates. Denitrification (74.95–100 %) was the dominant process in total N removal, while coupled nitrification-denitrification accounted for a higher proportion (45.68–97.05 %) of denitrification, indicating that coupling between nitrification and denitrification played a dominant role in N removal. In addition to dissolved oxygen levels, carbon and N substrate availabilities were also important variables to regulate N transformations. Overall, this study advanced our knowledge of the distribution patterns and controlling factors of N removal processes and highlighted that coupled nitrification-denitrification might have a significant but neglected role in N removal from periodically low-oxygen estuaries.

Immunofluorescence-Based Method to Assess Cancer Biomarker in the Hypoxic Region of the Tumor.

The development of novel imaging technologies allows the analysis of the expression and spatial distribution of multiple markers simultaneously, providing necessary information about a cellular identity and the surrounding microenvironment. This chapter describes the utilization of immunofluorescence to identify such biomarkers in fixed tissue from prostate cancer (PCa) xenografts. One such marker detectable by immunofluorescence is pimonidazole, which has been utilized to locate areas of low oxygen (hypoxia). Pimonidazole, in combination with other biomarkers, could be utilized to identify "niches" in the microenvironment harboring more aggressive cells both within and outside hypoxic areas. Specifically, we describe the method to use pimonidazole for the identification of hypoxic regions in PCa xenograft tumors along with CPT1A (carnitine palmitoyltransferase 1A) expression, an indicator of β-oxidation. This approach could be useful to characterize various biomarkers in the complex hypoxic tumor microenvironment.

Coral larvae avoid substratum exploration and settlement in low-oxygen environments

Oxygen is a critical resource that mediates a multitude of essential processes and interactions at multiple scales on coral reefs. In adult corals, it can directly or indirectly impact physiological processes, such as photosynthesis, respiration, and calcification. Moreover, many corals bleach as a consequence of being exposed to low oxygen. The sessile adult phase of corals makes habitat selection crucial for post-settlement survival and thus their pelagic larvae use a diverse array of cues to determine a suitable spot for settlement. However, the effects of oxygen on the early life stages of corals are still poorly known. This study investigated the importance of oxygen as a potential settlement cue and its effect on swimming and settlement behavior of coral larvae of two Acropora species. Two experiments were performed, one investigating coral larval swimming behavior under different oxygen conditions and the other studying coral larval settlement along an oxygen gradient. Bottom exploration, expressed as the percent of A. cytherea and A. pulchra larvae in the bottom section of experimental cylinders, was reduced by 96% and 100%, respectively, in hypoxic water compared to normoxic water. When offered the choice to settle on an otherwise preferred settlement substrate (Titanoderma prototypum) along an oxygen gradient, larvae of both coral species settled almost exclusively on T. prototypum fragments placed in well-oxygenated environments, with settlement rates increasing nonlinearly with oxygen concentrations. These results suggest that low-oxygen areas can negatively influence the settlement success of coral larvae and that oxygen concentration may be used as a cue for coral larval swimming and settlement behavior.

Impact of Lithium Salts on the Combustion Characteristics of Electrolyte under Diverse Pressures

The electrolyte is one of the components that releases the most heat during the thermal runaway (TR) and combustion process of lithium-ion batteries (LIBs). Therefore, the thermal hazard of the electrolyte has a significant impact on the safety of LIBs. In this paper, the combustion characteristics of the electrolyte such as parameters of heat release rate (HRR), mass loss rate (MLR) and total heat release (THR) have been investigated and analyzed. In order to meet the current demand of plateau sections with low-pressure and low-oxygen areas on LIBs, an electrolyte with the most commonly used lithium salts, LiPF6, was chosen as the experimental sample. Due to the superior low-temperature performance, an electrolyte containing LiBF4 was also selected to be compared with the LiPF6 sample. Combustion experiments were conducted for electrolyte pool fire under various altitudes. According to the experimental results, both the average and peak values of MLR in the stable combustion stage of the electrolyte pool fire had positive exponential relations with the atmospheric pressure. At the relatively higher altitude, there was less THR, and the average and peak values of HRR decreased significantly, while the combustion duration increased remarkably when compared with that at the lower altitude. The average HRR of the electrolyte with LiBF4 was obviously lower than that of solution containing LiPF6 under low atmospheric pressure, which was slightly higher for LiBF4 electrolyte at standard atmospheric pressure. Because of the low molecular weight (MW) of LiBF4, the THR of the corresponding electrolyte was larger, so the addition of LiBF4 could not effectively improve the safety of the electrolyte. Moreover, the decrease of pressure tended to increase the production of harmful hydrogen fluoride (HF) gas.

Linear and nonlinear analyses of normal and fatigue heart rate variability signals for miners in high-altitude and cold areas

Background and objectiveFatigue is an important cause of operational errors, and human errors are the main cause of accidents. This study is an exploratory study in China. Field tests were conducted on heart rate variability (HRV) parameters and physiological indicators of fatigue among miners in high-altitude, cold and low-oxygen areas. This paper studies heart activity patterns during work fatigue in miners. MethodsFatigue affects both the sympathetic and parasympathetic nervous systems, and it is expressed as an abnormal pattern of HRV parameters. Thirty miners were selected as subjects for a field test, and HRV was extracted from 60 groups of electrocardiography (ECG) datasets as basic signals for fatigue analysis. Then, we analyzed the HRV signals of the miners using linear (time domain and frequency domain) and nonlinear dynamics (Poincaré plot and sample entropy (SampEn)), and a Pearson's correlation coefficient analysis and t-tests were performed on the measured indices. ResultsThe results showed that the time-domain indices (SDNN, RMSSD, SDSD, pNN50, RRn, heart rate (HR), R-wave humps (RH)) and the coefficient of variation (CV)) and the frequency-domain indices (low frequency/high frequency (LF/HF), LFnorm and HFnorm) clearly changed after fatigue. These features were selected using a Poincaré plot, sample entropy, Pearson's correlation coefficient and a t-test for further analysis. The fatigue characteristics and sensitivity parameters of miners in a high-altitude, cold and hypoxic environment were obtained. ConclusionsThis study provides deep insight into the use of linear and nonlinear fatigue characteristics to effectively and reliably identify miner fatigue. Furthermore, the study provides a reference for clinical studies of acute mountain sickness in high-altitude, cold and hypoxic environments.

Uncovering diversity and metabolic spectrum of animals in dead zone sediments

Ocean deoxygenation driven by global warming and eutrophication is a primary concern for marine life. Resistant animals may be present in dead zone sediments, however there is lack of information on their diversity and metabolism. Here we combined geochemistry, microscopy, and RNA-seq for estimating taxonomy and functionality of micrometazoans along an oxygen gradient in the largest dead zone in the world. Nematodes are metabolically active at oxygen concentrations below 1.8 µmol L−1, and their diversity and community structure are different between low oxygen areas. This is likely due to toxic hydrogen sulfide and its potential to be oxidized by oxygen or nitrate. Zooplankton resting stages dominate the metazoan community, and these populations possibly use cytochrome c oxidase as an oxygen sensor to exit dormancy. Our study sheds light on mechanisms of animal adaptation to extreme environments. These biological resources can be essential for recolonization of dead zones when oxygen conditions improve.

Mast Cells Localize in Hypoxic Zones of Tumors and Secrete CCL-2 under Hypoxia through Activation of L-Type Calcium Channels.

Hypoxia is a condition that together with low pH, high amounts of reactive oxygen species (ROS), and increased adenosine levels characterize tumor microenvironment. Mast cells (MCs) are part of tumor microenvironment, but the effect of hypoxia on the production of MC-derived cytokines has not been fully described. Using the hypoxia marker pimonidazole in vivo, we found that MCs were largely located in the low-oxygen areas within B16-F1 mice melanoma tumors. In vitro, hypoxia promoted ROS production, a ROS-dependent increase of intracellular calcium, and the production of MCP 1 (CCL-2) in murine bone marrow-derived MCs. Hypoxia-induced CCL-2 production was sensitive to the antioxidant trolox and to nifedipine, a blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). Simultaneously with CCL-2 production, hypoxia caused the ROS-dependent glutathionylation and membrane translocation of the α1c subunit of Cav1.2 LVDCCs. Relationship between ROS production, calcium rise, and CCL-2 synthesis was also observed when cells were treated with H2O2 In vivo, high CCL-2 production was detected on hypoxic zones of melanoma tumors (where tryptase-positive MCs were also found). Pimonidazole and CCL-2 positive staining diminished when B16-F1 cell-inoculated animals were treated with trolox, nifedipine, or the adenosine receptor 2A antagonist KW6002. Our results show that MCs are located preferentially in hypoxic zones of melanoma tumors, hypoxia-induced CCL-2 production in MCs requires calcium rise mediated by glutathionylation and membrane translocation of LVDCCs, and this mechanism of CCL-2 synthesis seems to operate in other cells inside melanoma tumors, with the participation of the adenosine receptor 2A.

Enhanced Organic Carbon Burial in Sediments of Oxygen Minimum Zones Upon Ocean Deoxygenation

Oxygen minimum zones (OMZs) in the ocean are expanding. This expansion is attributed to global warming and may continue over the next 10 to 100 kyrs due to multiple climate CO$_\text{2}$-driven factors. The expansion of oxygen-deficient waters has the potential to enhance organic carbon burial in marine sediments, thereby providing a negative feedback on global warming. Here, we study the response of dissolved oxygen in the ocean to increased phosphorus and iron inputs due to CO$_\text{2}$-driven enhanced weathering and increased dust emissions, respectively. We use an ocean biogeochemical model coupled to a general ocean circulation model (the Hamburg Oceanic Carbon Cycle model, HAMOCC 2.0) to assess the impact of such regional deoxygenation on organic carbon burial in the modern ocean on time scales of up to 200~kyrs. We find that an increase in input of phosphorus and iron leads to an expansion of the area of the OMZ impinging on continental margin sediments and a significant decline in bottom water oxygen in the open ocean relative to pre-industrial conditions. The associated increase in organic carbon burial could contribute to the drawdown of $\sim$1600~Gt of carbon, which is equivalent to the total amount of CO$_\text{2}$ in the atmosphere predicted for the year 2100 in a business as usual scenario, on time scales of up to 50 kyrs. The corresponding areal extent of sediments overlain by bottom waters with little or no oxygen as estimated by the model is not very different from the minimum area estimated for two major oceanic anoxic events in Earth's past. Such events were associated with major perturbations of the oceanic carbon cycle, including high rates of organic carbon burial. We conclude that organic carbon burial in low oxygen areas in the ocean could contribute to removal of anthropogenic CO$_\text{2}$ from the atmosphere on long time scales.

Mesenchymal stem/stromal cells genetically engineered to produce vascular endothelial growth factor for revascularization in wound healing and ischemic conditions.

Mesenchymal stem/stromal cells (MSCs) may be able to improve ischemic conditions as they can actively seek out areas of low oxygen and secrete proangiogenic factors. In more severe trauma and chronic cases, however, cells alone may not be enough. Therefore, we have combined the stem cell and angiogenic factor approaches to make a more potent therapy. We developed an engineered stem cell therapy product designed to treat critical limb ischemia that could also be used in trauma-induced scarring and fibrosis where additional collateral blood flow is needed following damage to and blockage of the primary vessels. We used MSCs from normal human donor marrow and engineered them to produce high levels of the angiogenic factor vascular endothelial growth factor (VEGF). The MSC/VEGF product has been successfully developed and characterized using good manufacturing practice (GMP)-compliant methods, and we have completed experiments showing that MSC/VEGF significantly increased blood flow in the ischemic limb of immune deficient mice, compared to the saline controls in each study. We also performed safety studies demonstrating that the injected product does not cause harm and that the cells remain around the injection site for more than 1 month after hypoxic preconditioning. An on-demand formulation system for delivery of the product to clinical sites that lack cell processing facilities is in development.

Sensitivity of the simulated Oxygen Minimum Zone to biogeochemical processes at an oligotrophic site in the Arabian Sea

Oxygen minimum zones (OMZs) are large, low-oxygen areas in the global oceans. Although OMZs represent a serious threat to ecosystem functioning and services, our capability of modelling the main biogeochemical processes driving OMZ dynamic are still limited. Here we performed a full sensitivity analysis of a complex ecosystem model to rank the most important biogeochemical parameters influencing the simulation of the OMZ at an oligotrophic site in the open Arabian Sea. We applied a one-dimensional configuration of the European Regional Seas Ecosystem Model (ERSEM) - here advanced by including denitrification - coupled with the General Ocean Turbulence Model (GOTM). The coupled model was skilled in simulating the vertical gradients of climatological data of oxygen and nutrients. The sensitivity analysis of the model was carried out in two steps: i) a preliminary Morris screening analysis of 207 ERSEM parameters, which selected the three most influential groups of parameters; and ii) a subsequent Monte Carlo sampling-based analysis for ranking the importance of the 38 parameters within the three selected groups. Overall, the four most important parameters for the simulation of the minimum oxygen concentration were found to be: 1) the cubic half saturation constant for oxygenic control of denitrification; 2) the parameter regulating the fraction of ingested matter excreted by heterotrophic nanoflagellates; 3) the bacterial efficiency at low oxygen levels; and 4) the specific rate of bacterial release of capsular material. Based on these findings, and assuming that the ranking of the model parameters reflects the relevance of the process they characterize, we present a conceptual model describing the most important biogeochemical processes affecting the OMZ at the study site. Our results suggest that including bacteria explicitly in ecosystem models is useful to simulate and predict OMZs, provided that efforts are invested in estimating parameters characterizing the microbial loop in marine ecosystems.

On influencing factors of hypoxia in waters adjacent to the Changjiang estuary

Based on observational data from ten cruises carried out in 2012 and 2013, the distribution of dissolved oxygen (DO) and the evolution of hypoxia (DO concentrations < 2.0mgL−1) in waters adjacent to the Changjiang estuary are studied. The linkage between summer hypoxia and hydrodynamic conditions is explored. The results suggest that hypoxia frequently occurred from June to October to the south of the Changjiang estuary near the 30–50m isobaths and was prone to happening under strong stratification without the presence of the Kuroshio Subsurface Water (KSW). Over the Changjiang Bank, hypoxia mainly occurred in July, August and September. Low-oxygen areas initially appeared under strong stratification induced by the spreading of the Changjiang Diluted Water (CDW), and developed into hypoxic zones due to lack of DO replenishment from the relatively DO-rich Yellow Sea Water and the KSW. The yearly evolution of hypoxia was influenced by shelf circulation especially the path of the KSW in the bottom layer of the water to the south of the Changjiang estuary, and the extension of the CDW in the surface layer over the Changjiang Bank.

The effect of hypoxia on fish schooling.

Low-oxygen areas are expanding in the oceans as a result of climate change. Work carried out during the past two decades suggests that, in addition to impairing basic physiological functions, hypoxia can also affect fish behaviour. Given that many fish species are known to school, and that schooling is advantageous for their survival, the effect of hypoxia on schooling behaviour may have important ecological consequences. Here, we review the effects of hypoxia on school structure and dynamics, together with the mechanisms that cause an increase in school volume and that ultimately lead to school disruption. Furthermore, the effect of hypoxia generates a number of trade-offs in terms of schooling positions and school structure. Field observations have found that large schools of fish can exacerbate hypoxic conditions, with potential consequences for school structure and size. Therefore, previous models that predict the maximum size attainable by fish schools in relation to oxygen levels are also reviewed. Finally, we suggest that studies on the effect of hypoxia on schooling need to be integrated with those on temperature and ocean acidifications within a framework aimed at increasing our ability to predict the effect of multiple stressors of climate change on fish behaviour.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'.

Fermentation and Hypoxia Ensure Colorant and Synergistic Adverse Impacts on the Evolution, Survival, and Transfiguration of Premature Existence Phase Bivalves

Low oxygen precincts in beach front and vast sea biological systems have extended in late decades, a pattern that will quicken with climatic warming. There is developing acknowledgment that low oxygen areas of the sea are additionally fermented, a condition that will increase with rising levels of barometrical CO2. By and by, be that as it may, the simultaneous impacts of low oxygen and fermentation on marine life forms are to a great extent obscure, as earlier investigations of marine hypoxia have not considered pH levels. Later stage shellfishes were impervious to hypoxia or fermentation independently however experienced fundamentally (40%) diminished development rates when presented to both conditions at the same time. All things considered, these discoveries show that the outcomes of low oxygen and fermentation for early life organize bivalves, and likely other marine living beings, are more serious than would be anticipated by either singular stressor and in this manner must be viewed as together while surveying how sea creatures react to these conditions both today and under future environmental change situations.

3-D habitat suitability of jack mackerel Trachurus murphyi in the Southeastern Pacific, a comprehensive study

South Pacific jack mackerel, Trachurus murphyi, has an ocean-scale distribution, from the South American coastline to New Zealand and Tasmania. This fish, captured by Humans since the Holocene, is nowadays heavily exploited and its population has decreased substantially since the mid-1990s. The uncertainty associated to jack mackerel population structure currently hampers management. Several hypotheses have been proposed from a single population up to several discrete populations. Still no definitive answer was given. Determining how environmental conditions drive jack mackerel distribution can provide insights on its population structure. To do so, here we performed in three steps. First, we used satellite data to develop a statistical model of jack mackerel horizontal habitat suitability. Model predictions based on interaction between temperature and chlorophyll-a match the observed jack mackerel distribution, even during extreme El Niño event. Second, we studied the impact of oxygen and show that jack mackerel distribution and abundance is correlated to oxygen over a wide variety of scales and avoid low oxygen areas and periods. Third, on the basis of the above we built a conceptual 3D model of jack mackerel habitat in the Southeastern Pacific. We reveal the presence of a low suitable habitat along the Chilean and Peruvian coast, figuratively presenting a closed door caused by a gap in the horizontal habitat at ∼19–22°S and a shallow oxycline off south-centre Peru. This kind of situation likely occurs on a seasonal basis, in austral summer but also at longer temporal scales. A lack of exchanges at some periods/seasons partially isolate jack mackerel distributed off Peru. On the other hand the continuity in the habitat during most of the year explains why exchanges occur. We conclude that the more likely population structure for jack mackerel is a pelagic metapopulation.

The role of red blood cell S-nitrosation in nitrite bioactivation and its modulation by leucine and glucose

Previous work has shown that red blood cells (RBCs) reduce nitrite to NO under conditions of low oxygen. Strong support for the ability of red blood cells to promote nitrite bioactivation comes from using platelet activation as a NO-sensitive process. Whereas addition of nitrite to platelet rich plasma in the absence of RBCs has no effect on inhibition of platelet activation, when RBCs are present platelet activation is inhibited by an NO-dependent mechanism that is potentiated under hypoxia. In this paper, we demonstrate that nitrite bioactivation by RBCs is blunted by physiologically-relevant concentrations of nutrients including glucose and the important signaling amino acid leucine. Our mechanistic investigations demonstrate that RBC mediated nitrite bioactivation is largely dependent on nitrosation of RBC surface proteins. These data suggest a new expanded paradigm where RBC mediated nitrite bioactivation not only directs blood flow to areas of low oxygen but also to areas of low nutrients. Our findings could have profound implications for normal physiology as well as pathophysiology in a variety of diseases including diabetes, sickle cell disease, and arteriosclerosis.

Archaeal enrichment in the hypoxic zone in the northern Gulf of Mexico.

Areas of low oxygen have spread exponentially over the past 40 years, and are cited as a key stressor on coastal ecosystems. The world's second largest coastal hypoxic (≤ 2 mg of O2 l(-1)) zone occurs annually in the northern Gulf of Mexico. The net effect of hypoxia is the diversion of energy flow away from higher trophic levels to microorganisms. This energy shunt is consequential to the overall productivity of hypoxic water masses and the ecosystem as a whole. In this study, water column samples were collected at 39 sites in the nGOM, 21 of which were hypoxic. Analysis of the microbial community along a hypoxic to oxic dissolved oxygen gradient revealed that the relative abundance (iTag) of Thaumarchaeota species 16S rRNA genes (> 40% of the microbial community in some hypoxic samples), the absolute abundance (quantitative polymerase chain reaction; qPCR) of Thaumarchaeota 16S rRNA genes and archaeal ammonia-monooxygenase gene copy number (qPCR) were significantly higher in hypoxic samples. Spatial interpolation of the microbial and chemical data revealed a continuous, shelfwide band of low dissolved oxygen waters that were dominated by Thaumarchaeota (and Euryarchaeota), amoA genes and high concentrations of phosphate in the nGOM, thus implicating physicochemical forcing on microbial abundance.

Abundance of oceanic sea skaters, Halobates in the tropical Indian Ocean with respect to surface chlorophyll and oxygen concentrations

This study aims to clarify the relationship between environmental factors and the abundance of oceanic sea skaters, Halobates mostly H. micans. Samplings were performed in the tropical Indian Ocean at 15 stations along a straight line from 04°09′S, 094°26′E to 16°39′S, 065°15′E in October–November, 2010 with a Neuston net with CTD casting. A significant positive correlation was seen between chlorophyll concentration and number of Halobates individuals (mostly H. micans) collected, while a significant negative correlation was seen between oxygen concentration and number of individuals. More food such as zooplankton available to sea skaters in high-chlorophyll and low-oxygen areas may lead to higher population densities. Neuston net samplings were also taken around a fixed station, 8°S, 80°30′E in September–October 2011. The larval density of H. micans tended to be higher in spots where the air temperature was between 27.5°C and 28.0°C than in spots where it was between 25°C and 27°C. Reproductive and growth activities of H. micans may be affected by even a relatively small variation in air temperature in the spots they inhabit even at the fixed point 8°S, 80°30E in the Indian Ocean.

Hypoxic pulmonary vasoconstriction as a contributor to response in acute pulmonary embolism.

Hypoxic pulmonary vasoconstriction (HPV) is an adaptive response unique to the lung whereby blood flow is diverted away from areas of low alveolar oxygen to improve ventilation-perfusion matching and resultant gas exchange. Some previous experimental studies have suggested that the HPV response to hypoxia is blunted in acute pulmonary embolism (APE), while others have concluded that HPV contributes to elevated pulmonary blood pressures in APE. To understand these contradictory observations, we have used a structure-based computational model of integrated lung function in 10 subjects to study the impact of HPV on pulmonary hemodynamics and gas exchange in the presence of regional arterial occlusion. The integrated model includes an experimentally-derived model for HPV. Its function is validated against measurements of pulmonary vascular resistance in normal subjects at four levels of inspired oxygen. Our results show that the apparently disparate observations of previous studies can be explained within a single model: the model predicts that HPV increases mean pulmonary artery pressure in APE (by 8.2±7.0% in these subjects), and concurrently shows a reduction in response to hypoxia in the subjects who have high levels of occlusion and therefore maximal HPV in normoxia.

Tumorigenesis: cell defense against hypoxia?

Microenvironmental elements can directly contribute to the induction and the maintenance of tumor. Oxygen is the main element in the cell microenvironment and hypoxia can affect the process of tumorigenesis. In response to hypoxia, cells change their pattern and characteristics. These changes suggest that it is not just adaptation, but some sort of cell defense against hypoxia. If hypoxia is corrected, then cell defense mechanisms are interrupted. An examination of the process of tumorigenesis helps to design better therapeutic strategies. A systematic review of the English literature was conducted by searching PubMed, Google Scholar, and ISI Web databases for studies on changes that defend and help cells to live in a hypoxic microenvironment. Cells respond to hypoxia by de-differentiation and an increase in heat shock proteins. Angiogenesis and deviation of inflammatory response in favor of hypoxic cell survival also defend and save the oxygen-starved cells from death. Finally, anti-angiogenic therapies and more hypoxia enhance metastasis, as tumors with low oxygen concentration are more malignant than tumors with high oxygen concentration. All these enable cells to migrate away from low oxygen areas and seek a more conducive microenvironment. Therapies that make the microenvironment more hypoxic need to be revised. This has been done for anti-angiogenic therapies, previously considered to be anti-tumor approaches. Effective therapies may be correcting therapies which direct the tumor microenvironment towards natural physical/chemical condition. Correcting therapies either bring back tumor cells to a normal form (correct tumor cells) or help the immune system to eradicate tumor cells which can not be corrected.