Effects Of Prolonged Hypoxia Research Articles

Worth the risk? Effects of prolonged hypoxia and hypercapnia on ventilatory responses in patients with bilateral resection of the carotid bodies.

Worth the risk? Effects of prolonged hypoxia and hypercapnia on ventilatory responses in patients with bilateral resection of the carotid bodies.

OR-030 Influences of Four Weeks Intermittent Hypoxic Training on Aerobic Ability of High-Level Race Walking Athletes

OR-030 Influences of Four Weeks Intermittent Hypoxic Training on Aerobic Ability of High-Level Race Walking Athletes

Effects of prolonged hypoxia and bed rest on appetite and appetite-related hormones

Environmental hypoxia and inactivity have both been shown to modulate appetite. To elucidate the independent and combined effects of hypoxia and bed rest-induced inactivity on appetite-related hormones and subjective appetite, eleven healthy, non-obese males underwent three experimental interventions in a cross-over and randomized fashion: 1) Hypoxic confinement combined with daily moderate-intensity exercise (HAMB, FiO2 = 0.141 ± 0.004; PiO2 = 90.0 ± 0.4 mmHg) 2) Bed rest in normoxia (NBR, FiO2 = 0.209; PiO2 = 133.1 ± 0.3 mmHg) and 3) Bed rest in hypoxia (HBR, FiO2 = 0.141 ± 0.004; PiO2 = 90.0 ± 0.4 mmHg). A mixed-meal tolerance test (MTT), followed by an ad libitum meal were performed before (Pre) and after 16-days (Post) of each intervention. Composite satiety scores (CSS) during the MTT were calculated from visual analogue scores, while fasting and postprandial concentrations of total ghrelin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and leptin were quantified from arterialized-venous samples. Postprandial CSS were significantly lower at Post compared to Pre in NBR only (P < 0.05) with no differences observed in ad libitum meal intakes. Postprandial concentrations and incremental area under the curve (AUC) for total ghrelin and PYY were unchanged following all interventions. Postprandial GLP-1 concentrations were only reduced at Post following HBR (P < 0.05) with resulting AUC changes being significantly lower compared to HAMB (P < 0.01). Fasting leptin was reduced following HAMB (P < 0.05) with no changes observed following NBR and HBR. These findings suggest that independently, 16-day of simulated altitude exposure (∼4000 m) and bed rest-induced inactivity do not significantly alter subjective appetite or ad libitum intakes. The measured appetite-related hormones following both HAMB and HBR point to a situation of hypoxia-induced appetite stimulation, although this did not reflect in higher ad libitum intakes.Clinical Trial Registration Number:NCT02293772.

Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access.

Opioid overdose and mortality have increased at an alarming rate prompting new public health initiatives to reduce drug poisoning. One initiative is to expand access to the opioid antidote naloxone. Naloxone has a long history of safe and effective use by organized healthcare systems and providers in the treatment of opioid overdose by paramedics/emergency medicine technicians, emergency medicine physicians and anesthesiologists. The safety of naloxone in a prehospital setting administered by nonhealthcare professionals has not been formally established but will likely parallel medically supervised experiences. Naloxone dose and route of administration can produce variable intensity of potential adverse reactions and opioid withdrawal symptoms: intravenous administration and higher doses produce more adverse events and more severe withdrawal symptoms in those individuals who are opioid dependent. More serious adverse reactions after naloxone administration occur rarely and may be confounded by the effects of other co-intoxicants and the effects of prolonged hypoxia. One component of the new opioid harm reduction initiative is to expand naloxone access to high-risk individuals (addicts, abusers, or patients taking high-dose or extended-release opioids for pain) and their close family or household contacts. Patients or their close contacts receive a naloxone prescription to have the medication on their person or in the home for use during an emergency. Contacts are trained on overdose recognition, rescue breathing and administration of naloxone by intramuscular injection or nasal spraying of the injection prior to the arrival of emergency medical personnel. The safety profile of naloxone in traditional medical use must be considered in this new context of outpatient prescribing, dispensing and treatment of overdose prior to paramedic arrival. New naloxone delivery products are being developed for this prehospital application of naloxone in treatment of opioid overdose and prevention of opioid-induced mortality.

Pulse oximetry newborn screening for congenital heart defects. Is it really useful?

Congenital heart diseases (CHDs) are the most common birth defects, occurring in 8–9/1,000 live births and they represent one of the leading cause of infant death in the developed countries. A timely diagnosis is beneficial as even most critical cases can be successfully repaired by cardiac surgery or interventional catheterization procedures or may undergo a satisfactory palliation. Conversely, a delayed diagnosis may expose patients to the detrimental effects of prolonged hypoxia or hypoperfusion, worsen the preoperative condition and ultimately increase the risk of death or neurological sequelae [1]. With the advances in prenatal care many cases of CHDs are nowadays detected before birth. Nevertheless, the effectiveness of antenatal ultrasound screening is still not optimal and the detection rate of CHDs currently does not exceed 70% in the best case series.

Effect of prolonged hypoxia in autotrophic conditions in the hydrogen production by the green microalga Chlamydomonas reinhardtii in photobioreactor

In the context of hydrogen production by the green alga Chlamydomonas reinhardtii, the control of light attenuation conditions is used to set-up anoxia under illuminated and autotrophic conditions, without affecting photosynthetic capacities of cells (as with sulphur deprivation or PSII inhibitors like DCMU). This paper presents a full description of the protocol where the incident photons flux density (PFD) is adapted during cultivation in order to obtain a sufficiently low illuminated fraction γ under 0.25 leading to anoxic hydrogen producing conditions during several days. The protocol is validated in a torus-shape photobioreactor (PBR) revealing after few days of anoxic conditions a peak of hydrogen production (1.44 ml H2/h/l of culture; [0.8-1.0] ml H2/h/g of dry weight biomass) concomitant with a decrease of biomass concentration, protein content and maximal photosynthetic yield. Effect of over-accumulating starch, as being known to increase hydrogen production by the PSII-independent pathway, is also investigated.

Increased hexose transport in the roots of tomato plants submitted to prolonged hypoxia

We investigated the effects of prolonged hypoxia on the sugar uptake in tomato (Solanum lycopersicum L. var. MP-1) roots. Hydroponic cultures of whole tomato plants were submitted to hypoxic treatment for 1 week, and the roots were analyzed for sugar concentrations, hexose uptake and hexose transporter expression level. Contrary to what has been observed after anoxic shock or short-term hypoxic treatment, we show that sugar concentrations increase and hexose uptake is up-regulated in the roots after 1 week of hypoxic treatment. Increased hexose transport is concomitant with the induction of the hexose transporter gene LeHT2. These responses may be due either to a direct effect of low O(2) supply, or to a secondary effect associated with the increase in sugar concentrations, which, typically, develops in most hypoxic plants.

Effect of prolonged hypoxia on food consumption, respiration, growth and reproduction in marine scavenging gastropod Nassarius festivus

The effects of prolonged exposure to reduced oxygen levels (3.0 and 1.5 mg O 2 l −1) on marine scavenging gastropods Nassarius festivus were studied for 8 weeks. The percentages of individuals engaged in feeding and amount of food consumed were reduced as oxygen level decreased; absorption efficiency, however, did not vary significantly with oxygen level. Oxygen consumption rates and specific oxygen consumption rates were lower at reduced oxygen levels. Reproduction occurred at all oxygen levels with less egg capsules being produced at lower oxygen levels. Egg size and number of eggs per capsule, however, were not significantly affected by oxygen level. The increase in shell length was 12%, 6% and 5% at 6.0 mg O 2 l −1 (normoxia), 3.0 mg O 2 l −1 and 1.5 mg O 2 l −1, respectively. At the end of the experiment, the amount of energy allocated to growth and reproduction decreased at reduced oxygen levels with values obtained at 3.0 mg O 2 l −1 and 1.5 mg O 2 l −1 being 48% and 70% lower than those at 6.0 mg O 2 l −1. At all oxygen levels, most of the accumulated energy was allocated to shell growth and reproduction, and the amount allocated to somatic growth was relatively insignificant. The reduction in energy allocated to reproduction was greater than that to shell growth as the oxygen level was reduced, indicating a strategic energy allocation of marine scavengers under stressful conditions to enhance survival.

Constitutive/Hypoxic Degradation of HIF-α Proteins by the Proteasome Is Independent of von Hippel Lindau Protein Ubiquitylation and the Transactivation Activity of the Protein

Constitutive/Hypoxic Degradation of HIF-α Proteins by the Proteasome Is Independent of von Hippel Lindau Protein Ubiquitylation and the Transactivation Activity of the Protein

Central Necrosis in Isolated Hypoxic Human Pancreatic Islets: Evidence for Postisolation Ischemia

A variety of explanations have been provided to elucidate the requirement of the large islet mass that is essential for a successful treatment of patients with type I diabetes by intrahepatic transplantation. The purpose of this study was to investigate islet cell survival under the effect of prolonged hypoxia and/or nutrient withdrawal, which mimics posttransplantation environment of transplanted islets in the liver. We studied the influence of 24 h of hypoxia (1% O2) in intact isolated human and rat islets as well as the effect of combined oxygen/nutrient deprivation in a mouse insulinoma cell line (MIN6). In intact human islets, 24 h of hypoxia led to central necrosis combined with apoptotic features such as nuclear pyknosis and DNA fragmentation. In the course of hypoxic treatment, ultrastructural analysis demonstrated a gradual transition from an apoptotic to a necrotic morphology particularly pronounced in central areas of large islets. In MIN6 cells, on the other hand, hypoxia led to a twofold (p < 0.01) increase in caspase-3 activity, an indicator of apoptosis, but not to necrosis, as determined by release of lactate dehydrogenase (LDH). Only in combination with nutrient/serum deprivation was a marked increase in LDH release observed (sixfold vs. control, p < 0.01). We therefore conclude that, similar to MIN6 cells, central necrosis in isolated hypoxic islets is the result of the combined effects of hypoxia and nutrient/serum deprivation, most likely due to limited diffusion. Provided that transplanted islets undergo a similar fate as shown in our in vitro study, future emphasis will require the development of strategies that protect the islet graft from early cell death and accelerate the revascularization process.

Chronic Hypoxia Induces Apoptosis in Cardiac Myocytes: A Possible Role for Bcl-2-like Proteins

The effect of prolonged hypoxia as well as the molecular mechanisms on cardiac cell death is not well established. A possible role of Bcl-2 and Bax in hypoxia-induced apoptosis in different cell types has been proposed. Here we demonstrate the effect of hypoxia on the induction of apoptosis and the expression of Bcl-2-like proteins in vivo and in vitro. Hearts from rats exposed to chronic hypoxia (n = 4) showed an increased rate of apoptosis compared to normoxic hearts (n = 4). The induction of apoptosis in hypoxic hearts correlated with a significant decrease of Bcl-2 protein level, whereas Bax protein expression was increased. Exposure of isolated neonatal rat cardiac myocytes to hypoxia also resulted in a significant increase in apoptosis. However, Bcl-2 and Bax protein levels essentially remained unchanged. Our results may suggest a different molecular mechanism of hypoxia-induced apoptosis in vivo and in vitro.

Effect of prolonged hypoxia on Na + channel mRNA subtypes in the developing rat cortex

Voltage-gated Na + channels are regulated in response to oxygen deprivation in the mammalian cortex. Past investigations have demonstrated that Na + channel protein expression is up-regulated in the immature brain exposed to prolonged hypoxia. Since it is unknown as to which Na + channel subtype(s) is involved in this regulation, we used RT-PCR to assess the effect of hypoxia on Na + channel I, II and III α-subunit mRNA expression in the developing rat cortex. Na + channel II mRNA tended to increase during early development, whereas Na + channel I and III did not change or slightly decreased with age. Hypoxic exposure for 1-day had no effect on Na + channel expression, while 5-day hypoxia significantly increased Na + channel III density, with a slight increase in Na + channel I and no appreciable change in Na + channel II. These results suggest that Na + channel subtype expression in the developing cortex is differentially regulated in response to prolonged hypoxic exposure.

Persistent block of CA1 synaptic function by prolonged hypoxia

The effects of prolonged hypoxia were studied by field and intracellular recordings from hippocampal slices of the rat, kept submerged at 34°C. When artificial cerebrospinal fluid contained 10 mM glucose, even very long exposures to hypoxia or 300 μM cyanide (21–25 min) did not block field excitatory postsynaptic potentials and population spikes irreversibly. By contrast, in the presence of 4 mM glucose, hypoxia lasting only 9–13 min—ending 2–3 min after the characteristic transient recovery (“hypoxic injury potential”)—resulted in irreversible block of synaptic responses. Voltage-dependent sodium channels and N-methyl- d-aspartate receptors are involved, because irreversible block was prevented by tetrodotoxin (0.5 μM), kynurenate (2 mM) or dl-aminophosphonovalerate (50 μM), whereas 6,7-dinitroquinoxaline-2,3-dione (25 μM) suppressed only the transient recovery. The hypoxic suppression of afferent volleys in slices kept in 4 mM glucose was also prevented by kynurenate or aminophosphonovalerate. Intracellular recordings revealed opposite effects of hypoxia according to glucose concentration: in 10 mM glucose, mainly hyperpolarization; in 4 mM glucose, after a brief hyperpolarization, a major and usually irreversible depolarization. In the presence of kynurenate or tetrodotoxin, major depolarizations also occurred, but they were reversible. Thus, large depolarizations of hippocampal neurons do not necessarily lead to irreversible block of synaptic transmission: there is lasting damage only when hypoxia is combined with low glucose, presumably because a reduced supply of glycolytically generated ATP limits the Na +/K + pump's ability to maintain or restore membrane potentials and thus prevent excessive activation of N-methyl- d-aspartate receptors.

Effects of Prolonged Hypoxia, Reoxygenation, and Shear Stress on Bovine Aortic Endothelial Cell Prostacyclin Production

Bovine aortic endothelial cell prostacyclin production was assessed under conditions of shear stress, hypoxia, and reoxygenation. Methods: Endothelial cell cultures (n = 8) grown on microcarrier beads were sequentially exposed to 2 h of normoxia (O 2 = 20%), then 24 h of hypoxia (O 2 = 2%) and 2 h of reoxygenation (O 2 = 20%). Cell viability, levels of prostaglandin H 2 synthase protein, and prostacyclin production were evaluated. Results: Prostacyclin production decreased significantly after 1 h of hypoxia, and became undetectable after 24 h. Reoxygenation did not result in recovery of normoxic levels of prostacyclin production. Immunoblots revealed no change in the levels of prostaglandin H 2 synthase protein during hypoxia, and reoxygenation. Addition of arachidonic acid to cells (n = 5) during reoxygenation resulted in prompt recovery of prostacyclin synthesis. Conclusions: Endothelial cells exposed to sequential conditions of hypoxia and reoxygenation in the presence of shear stress decreased prostacyclin production. The decrease in prostacyclin production was not due to altered cell viability, levels of prostaglandin H 2 synthase, or inactivation of prostaglandin H 2 synthase.

Survival of synchronized human NHIK 3025 cells irradiated aerobically following a prolonged treatment with extremely hypoxic conditions

Purpose : To investigate whether radiation survival of cells irradiated aerobically in the oxygen-sensitive restriction point in late G1 is dependent on where in the cell cycle the cells first were rendered hypoxic. Materials and methods : Human cervix carcinoma, NHIK 3025 cells, were synchronized and rendered hypoxic while in early-, midor late G1 or in early G2. Cell-cycle progression during the treatment was monitored by flow cytometry, and cell survival following either hypoxia alone or hypoxia with subsequent reoxygenation and irradiation was measured by the ability of the cells to form macroscopic colonies. Results : During prolonged hypoxia, all surviving cells accumulated in an oxygen-sensitive restriction point in late G1. Cells rendered hypoxic in G2 initiated DNA synthesis following reoxygenation and irradiation several hours later than cells rendered hypoxic in G1. Radiation survival of cells accumulated in the oxygensensitive restriction point was independent of where in the cell cycle the cells first were rendered hypoxic. The hypoxia-treated cells had lower radiation survival probability than untreated cells in late G1. Conclusions : Although cells accumulated in the oxygen-sensitive restriction point from different parts of the cell cycle are not biologically identical, they are radiobiologically similar. The radiosensitizing effect of prolonged hypoxia was not merely due to cell-cycle redistribution.

Hypobaric hypoxia (380 Torr) decreases intracellular and total body water in goats

The effects of prolonged hypoxia on body water distribution was studied in four unanesthetized adult goats (Capra lircus) at sea level and after 16 days in a hypobaric chamber [(380 Torr, 5,500 m, 24 +/- 1 degrees C); arterial PO2 = 27 +/- 2 (SE) Torr]. Total body water (TBW), extracellular fluid volume (ECF), and plasma volume (PV) were determined with 3H2O, [14C]inulin, and indocyanine green dye, respectively. Blood volume (BV) [BV = 100PV/(100 - hematocrit)], erythrocyte volume (RCV) (RCV = BV - PV), and intracellular fluid (ICF) (ICF = TBW - ECF) and interstitial fluid (ISF) (ISF = ECF - PV) volumes were calculated. Hypoxia resulted in increased pulmonary ventilation and arterial pH and decreased arterial PCO2 and PO2 (P less than 0.05). In addition, body mass (-7.1%), TBW (-9.1%), and ICF volume (-14.4%) all decreased, whereas ECF (+11.7%) and ISF (+27.7%) volumes increased (P less than 0.05). The decrease in TBW accounted for 89% of the loss of body mass. Although PV decreased significantly (-15.3%), BV was unchanged because of an offsetting increase in RCV (+39.5%; P less than 0.05). We conclude that, in adult goats, prolonged hypobaric hypoxia results in decreases in TBW volume, ICF volume, and PV, with concomitant increases in ECF and ISF volumes.

Effects of prolonged hypoxia on adenylate cyclase activity and beta-adrenergic receptors in pulmonary and systemic arteries of the rat.

Prolonged hypoxia causes pulmonary hypertension but no change in systemic vasomotor tone. In an effort to define the mechanisms involved, we determined the effects of 3 and 7 days of hypoxia on adenylate cyclase activity and beta-adrenergic receptor binding characteristics in pulmonary and systemic arteries in an adult rat model of hypoxic pulmonary vasoconstriction produced by hypobaria. Basal and stimulated adenylate cyclase activity were measured in crude membrane preparations by radioimmunoassay for cyclic AMP. Basal enzyme activity in pulmonary arteries did not change with hypoxia, whereas in systemic arteries it increased 3.5- and 5.3-fold following 3 and 7 days of hypoxia, respectively. GTP-stimulated activity in pulmonary arteries also did not change, but in systemic arteries it increased 7.1- and 5.5-fold. Isoproterenol-stimulated activity in pulmonary arteries was decreased to 49% of control-stimulated activity following 3 days but was similar to control-stimulated activity after 7 days of hypoxia; in systemic arteries it increased 5.6- and 4.6-fold. Sodium fluoride-stimulated activity in pulmonary arteries was unchanged, whereas in systemic arteries it increased 3.8- and 5.3-fold. In contrast, forskolin-stimulated activity, which also was not altered in pulmonary arteries, was increased by only 85% and 71% in systemic arteries. beta-Adrenergic receptors were studied with [125I]iodocyanopindolol. Seven days of hypoxia decreased receptor density by 37% and 57% in the pulmonary and systemic arteries, respectively. Receptor affinity for agonists was not altered. Thus, despite downregulation of beta-adrenergic receptors in both artery types, prolonged hypoxia has no sustained effect on adenylate cyclase activity in pulmonary arteries, whereas enzyme activity in systemic arteries is markedly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of prolonged hypoxia on striated muscle pH regulation.

The extracellular acid-base status of mammals exposed to low inspired PO2 for prolonged periods of time has been studied extensively (Bouverot, 1985). However, less is known regarding the intracellular acid-base status during prolonged hypoxia. In a previous study we observed that the intracellular pH of striated muscles of rats subjected to 3 weeks of hypobaric hypoxia was not significantly different from that of normoxic rats (Gonzalez and Clancy, 1986b). However, when the cells were acid-loaded by rendering the animals hypercapnic, the decreases in intracellular pH of tibialis anterior, quadriceps and diaphragm were significantly less than in hypercapnic normoxic rats. The magnitude of cell pH regulation, as measured by the apparent non-bicarbonate buffer value, ranged from 3 (tibialis anterior) to 12 (diaphragm) times greater in the hypobaric hypoxic than the normoxic animals. This augmentation of striated muscle pH regulation during hypercapnia in hypobaric hypoxic rats could result from increased physicochemical buffering and/or increased efflux of proton equivalents. The question arises as to whether augmentation of these cellular pH- regulating mechanisms resulted from intrinsic changes in the cell interior and/or the sarcolemma engendered by the prolonged hypoxia or whether extracellular factors which enhance these cellular pH-regulating mechanisms were increased to a greater extent in the hypercapnic hypoxic rats than in the hypercapnic normoxic rats. To resolve this question cell pH regulation of diaphragms from prolonged hypoxic and normoxic rats was studied under in vitro conditions. Under these conditions the contribution of extracellular factors to cell pH regulation was the same in diaphragms from hypoxic and normoxic rats. Therefore, any difference in cell pH regulation should be attributable to intrinsic changes in one or more of the cell pH-regulating mechanisms.

The effect of prolonged hypoxia on growth and viability of Chinese hamster cells

The colony forming ability and cell proliferation kinetics of Chinese hamster cells growing under continuous prolonged hypoxia have been studied. The colony forming ability decreases rapidly according to a time-power-function. Cell multiplication ceases gradually while profound changes in the progression through the various stages of the cell cycle take place. The prominent effect is a four- to five-fold increase in the duration of the S phase and a nine-fold increase in the duration of the G 1 phase.

Effects of hypoxia, hypotension, and acidosis on the electrolyte composition of rat kidneys.

The effect of prolonged hypoxia, transient and prolonged hypotension, and of acidosis on rat kidney and muscle water, sodium, potassium, magnesium, and phosphate composition was investigated. A signif