Periods Of Hypoxia Research Articles

Prevention of Neurodegenerative Damage to the Brain in Rats in Experimental Alzheimer’s Disease by Adaptation to Hypoxia

We report here studies addressing the possibility of preventing neurodegenerative changes in the brain using adaptation to periodic hypoxia in rats with experimental Alzheimer's disease induced by administration of the neurotoxic peptide fragment of beta-amyloid (Ab) into the basal magnocellular nucleus. Adaptation to periodic hypoxia was performed in a barochamber (4000 m, 4 h per day, 14 days). The following results were obtained 15 days after administration of Ab. 1. Adaptation to periodic hypoxia significantly blocked Ab-induced memory degradation in rats, as assessed by testing a conditioned passive avoidance reflex. 2. Adaptation to periodic hypoxia significantly restricted increases in oxidative stress, measured spectrophotometrically in the hippocampus in terms of the content of thiobarbituric acid-reactive secondary lipid peroxidation products. 3. Adaptation to periodic hypoxia completely prevented the overproduction of NO in the brains of rats with experimental Alzheimer's disease, as measured in terms of increases in tissue levels of stable NO metabolites, i.e., nitrites and nitrates. 4. The cerebral cortex of rats given Ab injections after adaptation to periodic hypoxia did not contain neurons with pathomorphological changes or dead neurons (Nissl staining), which were typical in animals with experimental Alzheimer's disease. Thus, adaptation to periodic hypoxia effectively prevented oxidative and nitrosative stress, protecting against neurodegenerative changes and protecting cognitive functions in experimental Alzheimer's disease.

Preconditioning the diabetic human myocardium

Our objective was to determine whether human diabetic myocardium is amenable to the cardioprotective actions of ischaemic preconditioning. Human right atrial appendages were harvested from diabetic and non-diabetic patients undergoing elective coronary artery bypass graft surgery. The atrial trabeculae were isolated and subjected to 90 min. of hypoxia followed by 120 min. of reoxygenation, following which the percentage recovery of baseline contractile function was determined. The atrial trabeculae were randomized to: (i) controls (groups 1 and 3); (ii) standard hypoxic preconditioning (HPC) protocol consisting of 4 min. of hypoxia/16 min. of reoxygenation before the 90 min. index hypoxic period (groups 2 and 4); (iii) Prolonged HPC protocol consisting of: 7 min. of hypoxia /16 min. of reoxygenation before the index hypoxic period (group 5). In addition, basal levels of Akt phosphorylation were determined in right atrial appendages harvested from non-diabetic patients and diabetic patients to determine whether PI3K-Akt signalling is down-regulated in the diabetic heart. Standard HPC improved baseline contractile function in human atrial trabeculae harvested from non-diabetic patients (52.4 ± 3.8% with HPC versus 30.0 ± 3.2% in control: P= 0.001; N= 6/group), but not in atrial trabeculae isolated from diabetic patients (22.6 ± 3.3% with HPC versus 28.5 ± 1.9% in control: P > 0.05; N= 6/group). However, the prolonged HPC protocol did improve baseline contractile function in atrial trabeculae harvested from diabetic patients (42.0 ± 2.4% with HPC versus 28.5 ± 1.9% in control: P= 0.001; N≥ 6/group). Western blot analysis demonstrated lower levels of phosphorylated Akt in diabetic myocardium compared to non-diabetic myocardium (0.13 ± 0.03 arbitrary units versus 0.39 ± 0.11 arbitrary units: P= 0.047; N≥ 4/group). From the data obtained it appears that the threshold for preconditioning the diabetic myocardium is elevated which may be related to the down-regulation of the PI3K-Akt pathway.

Role of 70-kDa Ribosomal Protein S6 Kinase, Nitric Oxide Synthase, Glycogen Synthase Kinase-3β, and Mitochondrial Permeability Transition Pore in Desflurane-induced Postconditioning in Isolated Human Right Atria

Desflurane during early reperfusion has been shown to postcondition human myocardium. Whether it involves "reperfusion injury salvage kinase" pathway remains incompletely studied. The authors tested the involvement of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, glycogen synthase kinase (GSK)-3beta, and mitochondrial permeability transition pore in desflurane-induced postconditioning. The authors recorded isometric contraction of human right atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of rapamycin, a 70-kDa ribosomal protein S6 kinase inhibitor, NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, and atractyloside, the mitochondrial permeability transition pore opener. GSK-3beta inhibitor VII was administered during the first few minutes of reoxygenation alone or in the presence of desflurane 6%, rapamycin, NG-nitro-L-arginine methyl ester, and atractyloside. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- SD). Phosphorylation of GSK-3beta was measured using blotting. Desflurane 6% (84 +/- 4% of baseline) enhanced the recovery of force after 60 min of reoxygenation when compared with the control group (54 +/- 4%, P < 0.0001). Rapamycin (68 +/- 8% of baseline), NG-nitro-L-arginine methyl ester (57 +/- 8%), atractyloside (52 +/- 7%) abolished desflurane-induced postconditioning (P < 0.001). GSK-3beta inhibitor-induced postconditioning (84 +/- 5%, P < 0.0001 vs. control) was not modified by desflurane (78 +/- 6%), rapamycin (81 +/- 6%), and NG-nitro-L-arginine methyl ester (82 +/- 10%), but it was abolished by atractyloside (49 +/- 6%). Desflurane increased the phosphorylation of GSK-3beta (3.30 +/- 0.57-fold increase in desflurane vs. control; P < 0.0001). In vitro, desflurane-induced postconditioning protects human myocardium through the activation of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, inhibition, and phosphorylation of GSK-3beta, and preventing mitochondrial permeability transition pore opening.

Hydrogen sulfide attenuates intestinal ischemia‐reperfusion injury when delivered in the post‐ischemic period

To investigate whether pharmacologic post-conditioning of intestinal tissue with hydrogen sulfide (HS) protects against ischemia reperfusion injury (IRI). In vitro, enterocytes were made hypoxic for 1, 2, or 3 h, treated with media containing between 0 and 100 µM HS 20 min prior to the end of the hypoxic period, then returned to normoxia for 3 h. An apoptotic index (AI) was determined for each time point and (HS). In vivo, jejunal ischemia was induced in male Sprague-Dawley rats for 1, 2, or 3 h; 20 min prior to the end of the ischemic period animals were given an intravenous injection of NaHS sufficient to raise the bloodstream concentration to 0, 10 µM, or 100 µM HS. This was followed by jejunal reperfusion for 3 h, histologic processing, and measurement of villus height. In vitro, there was a significant decrease in AI compared with non-HS-treated control at all time points after treatment with 10 µM HS, and at the 2 h time point with 100 µM HS (P < 0.017). In vivo, after 1 h ischemia, qualitative reduction of injury was noted with 10 µM and 100 µM; after 2 h ischemia, reduction was noted with 10 µM but not 100 µM; and after 3 h ischemia, there was no injury reduction. HS treatment resulted in significant quantitative preservation (P < 0.05) of villus height at all time points and doses, except for 3 h ischemia and delivery of 100 µM (P = 0.129). Hydrogen sulfide provides significant protection to intestinal tissues in vitro and in vivo when delivered after the onset of ischemia.

Effect of different stress factors on some physiological parameters of Nile tilapia ( Oreochromis niloticus)

This study was conducted to determine the effect of different stress factors on some physiological measurements of Nile tilapia ( Oreochromis niloticus). A total number of 160 Nile tilapia, the body weight ranging between 100 and 120 g, were exposed to three stress factors of hypoxia, overcrowding and starvation for different periods 24, 72 and 144 h. The results of cortisol level were 134.15, 144.27, 154.12 ng/ml and 140.18 ng/ml for control, hypoxia, overcrowding and starvation, respectively, while after 144 h did not show significant difference among treatments compared with control group. In contrast, the values of T 3 and T 4 observed reduction with significant difference that T 3 ranged between the highest value 122.12 ng/ml for control group to lowest value of starvation group 94.35, 93.81 and 88.46 ng/ml after 24, 72 and 144 h. Also, similar trend of results observed in T 4 and blood glucose among treatments. And the enzymatic activity of lactate dehydrogenise (LDH) increased in hypoxic group, while a significant reduction appeared in overcrowding and starved fish compared to control group. The pyruvate kinase (PK) activity decreased in hypoxic group but increased in other group.

Comparative Estimation of Tracheostomy Time and Procedures in Patients with Multiple Organ Dysfunction after Cardiosurgical Interventions

Objective: to comparatively evaluate the efficiency of tracheostomy by various methods in different artificial ventilation periods in patients with multiple organ dysfunction after cardiosurgical intervention. Subjects and methods. In the first stage, the patients in whom tracheostomy was performed in a classical surgical manner (a control group; n=15) not earlier than 7 days after arterial ventilation (AV) were compared. A study group comprised 19 patients in whom tracheostomy was carried out on days 3—4 after AV. In the second stage of the study, tracheostomy was made not later than 4 days following AV: by the puncture-dilatation method in study group 2 (n=28) and by the classical surgical procedure in control group 2 (n=49). Results. The time and procedures of an intervention were found to have an impact on the bacteriological profile of a patient, the duration of switch to spontaneous respiration, and the tracheobronchial tree. The advantages and disadvantages of the puncture-dilatation technique of tracheostomy were noted from the standpoint of hemodynamics, gas transport, possible complications, and long-term Results. Conclusion. Early tracheostomy caused a reduction in the number of infectious complications of the tracheobronchial tree, early decannulation with switch to spontaneous breathing. The puncture-dilatation procedure of tracheostomy is characterized by the minimum hypoxic period at cannula installation and ensures prompt healing in the absence of purulent complications. The classical surgical tracheostomy remains to be the method of choice during massive anticoagulant therapy. The accumulation of long-term results should be continued. Key words: tracheostomy, multiple organ dysfunction, cardiac surgery.

Spatial and temporal changes in estuarine water quality during a post-flood hypoxic event

A major fish kill occurred in the Richmond River estuary in January 2008 due to oxygen depletion following extensive overbank flooding. This paper examines spatial and temporal changes in the chemistry of main channel waters, thereby identifying the primary sources of deoxygenating water. Over 40 km of the mid- to lower estuary main channel was deoxygenated within seven days of the flood peak. Hypoxia was confined to downstream of the confluences with mid-estuary backswamp basins and occurred during the later phase of the flood recession. Water chemistry at key locations in the estuary indicated elevated concentrations of redox sensitive species associated with acid sulfate soils (ASS) during the hypoxic period. Peak concentrations of Fe 2+ up to 18.2 μmol L −1, dissolved Mn up to 4.3 μmol L −1, chemical oxygen demand (COD) up to 2052 μmol L −1, dissolved organic carbon (DOC) up to 960 μmol L −1 and elemental S 0 up to 4.7 μmol L −1 were found in the backswamp discharge confluences and mid-estuary main channel locations. The geochemical signature of main channel floodwaters identifies anaerobic decomposition of floodplain vegetation in ASS backswamps as a primary process leading to generation of hypoxic waters. The transport of these hypoxic floodwaters to the estuary has been accelerated and prolonged by extensive floodplain drainage, thereby enhancing the magnitude and duration of estuarine deoxygenation.

Determinants of quality of life in survivors of cardiac arrest

To study factors related to quality of life after a hypoxic period due to cardiac arrest. Retrospective cohort study. Eighty-eight survivors of out-of-hospital cardiac arrest, admitted to a Dutch academic hospital between 2001 and 2006. Patients received a set of questionnaires at home. The main outcome measures were physical and mental quality of life (Medical Outcomes Study 36-item Short Form Health Survey; SF-36). Potential determinants were cognitive complaints, emotional problems depression/anxiety), post-traumatic stress, fatigue, daily functioning and participation in society. Multiple linear regression analyses were performed with physical and mental quality of life as dependent variables. Sixty-three (72%) patients responded. Mean time since cardiac arrest was 36 months (standard deviation (SD) 19). Backward regression analyses showed that physical quality of life was significantly (p < 0.001, adjusted R2 = 0.531) related to cognitive complaints (beta = -0.378), instrumental daily life activities (beta = 0.262), post-traumatic stress (beta = -0.246) and fatigue (beta = -0.226). Mental quality of life was significantly (p < 0.001, adjusted R2 = 0.664) explained by anxiety/depression (beta = -0.609), fatigue (beta = -0.177) and cognitive complaints (beta = -0.175). Quality of life is related to cognitive complaints, fatigue, anxiety/depression, post-traumatic stress and difficulties in daily activities in survivors of out-of-hospital cardiac arrest. Rehabilitation programmes for this group should specifically address these topics.

Interval hypoxic training improves autonomic cardiovascular and respiratory control in patients with mild chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is associated with cardiac autonomic nervous system dysregulation. This study evaluates the effects of interval hypoxic training on cardiovascular and respiratory control in patients with mild COPD. In 18 eucapnic normoxic mild COPD patients (age 51.7 +/- 2.4 years, mean +/- SEM), randomly assigned to either training or placebo group, and 14 age-matched healthy controls (47.7 +/- 2.8 years), we monitored end-tidal carbon dioxide, airway flow, arterial oxygen saturation, electrocardiogram, and continuous noninvasive blood pressure at rest, during progressive hypercapnic hyperoxia and isocapnic hypoxia to compare baroreflex sensitivity to hypoxia and hypercapnia before and after 3 weeks of hypoxic training. In double-blind fashion, both groups received 15 sessions of passive intermittent hypoxia (training group) or normoxia (placebo group). For the hypoxia group, each session consisted of three to five hypoxic (15-12% oxygen) periods (3-5 min) with 3-min normoxic intervals. The placebo group inhaled normoxic air. Before training, COPD patients showed depressed baroreflex sensitivity, as compared with healthy individuals, without evident chemoreflex abnormalities. After training, in contrast to placebo group, the training group showed increased (P < 0.05) baroreflex sensitivity up to normal levels and selectively increased hypercapnic ventilatory response (P < 0.05), without changes in hypoxic ventilatory response. Eucapnic normoxic mild COPD patients already showed signs of cardiovascular autonomic abnormalities at baseline, which normalized with hypoxic training. If confirmed in more severe patients, interval hypoxic training may be a therapeutic strategy to rebalance early autonomic dysfunction in COPD patients.

Changes in Pituitary-Adrenal Function under Continuous Exposure to Hypoxia in Male Rats

The plasma corticosterone concentration and incorporation of 14C-1-acetate into adrenocortical hormones were measured in male rats exposed to hypoxia (12.5% O2 in N2 balance) for periods of 30 min--14 days. Hypoxia significantly increased the weight of the adrenal and pituitary glands in early stages of exposure. However, weight returned to the control level on the 14th day of exposure. Hypoxia consistently decreased the weight of the thymus. Hypoxia elevated the plasma corticosterone concentration in the early stages of exposure. However, the elevated corticosterone level gradually decreased by the 7th day. The corticosterone level at this stage was lower than in the control. The corticosterone concentration returned to the control level on the 14th day. Hypoxia significantly facilitated incorporation of 14C-1-acetate into corticosterone and cortisol in the adrenal homogenate. The elevated incorporation was maintained until the 7th day and gradually decreased to the control level there after. Body weight was decreased by hypoxia (12 gram in 24 hours). On the 5th day, the weight returned to the control level. Hematocrit increased gradually during 14 days of hypoxia exposure. These results suggest that pituitary-adrenal function is greatly facilitated by 1-6 hours of hypoxia exposure, and hypoxia acclimatization is accomplished humorally within 14 days of exposure in rats.

Autophagy is required during cycling hypoxia to lower production of reactive oxygen species

Background and purpose Human tumors are characterized by the presence of cells that experience periodic episodes of hypoxia followed by reoxygenation. These cells are exposed to reactive oxygen species (ROS) upon reoxygenation and require adaptation to this stress by lowering ROS production or enhancing ROS-clearance for their survival. We hypothesized that autophagy, a lysosomal degradation pathway, may be involved in reducing ROS during periodic hypoxia through removal of ROS producing species. Materials and methods Human tumor cells (MCF-7, HT29, U373) were exposed to cycles of hypoxia (O 2 < 0.02%) and reoxygenation in the absence or presence of the autophagy inhibitor chloroquine (CQ). Clonogenic survival, ROS production and mitochondrial-DNA content were assessed. In addition, A549 cells overexpressing wild-type or K63-mutated ubiquitin (K63R) were analyzed for ROS production. Results Our data indicate that CQ treatment sensitizes cells to cycling hypoxia, due to increased production of ROS, associated with an incapacity to reduce mitochondrial content. Addition of the ROS-scavenger N-acetyl-cysteine increased cell viability and neutralized CQ-effects. Additionally, genetic prevention of K63-linked ubiquitin chains that are required for the removal of toxic protein aggregates by autophagy, resulted in increased ROS production. Conclusions Inhibition of autophagy substantially increases cell death induced by cycling hypoxia through increased ROS production, providing an opportunity to decrease the hypoxic fraction within tumors and enhance tumor therapy.

Sevoflurane‐ and Desflurane‐induced human myocardial post‐conditioning through Phosphatidylinositol‐3‐kinase/Akt signalling

The role of phosphatidylinositol-3-kinase (PI3K) in sevoflurane- and desflurane-induced myocardial post-conditioning remains unknown. We recorded isometric contraction of isolated human right atrial trabeculae (oxygenated Tyrode's at 34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by a 60-min reoxygenation period. At the onset of reoxygenation, muscles were exposed to 5 min of sevoflurane 1%, 2%, and 3%, and desflurane 3%, 6%, and 9%. In separate groups, sevoflurane 2% and desflurane 6% were administered in the presence of 100 nM wortmannin, a PI3K inhibitor. Recovery of force after the 60-min reoxygenation period was compared between groups (mean +/- SD). As compared with the Control group (49 +/- 7% of baseline) PostC by sevoflurane 1%, 2%, and 3% (78 +/- 4%, 79 +/- 5%, and 85 +/- 4% of baseline, respectively) and desflurane 3%, 6%, and 9% (74 +/- 5%, 84 +/- 4%, and 86 +/- 11% of baseline, respectively) enhanced the recovery of force. This effect was abolished in the presence of wortmannin (56 +/- 5% of baseline for sevoflurane 2%+wortmannin; 56 +/- 3% of baseline for desflurane 6%+wortmannin). Wortmannin alone had no effect on the recovery of force (57 +/- 7% of baseline). In vitro, sevoflurane and desflurane post-conditioned human myocardium against hypoxia through activation of phosphatidylinositol-3-kinase.

Increased serum brain-derived neurotrophic factor protein upon hypoxia in healthy young men

Exposing animals to brief hypoxic periods leads to neuroprotective ischemic tolerance termed preconditioning. This phenomenon is well documented in the brain, but the underlying mechanisms require further elucidation. As nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important mediators of maintaining homeostatic conditions in the adult nervous system in terms of physiological and pathophysiological processes, we hypothesized that hypoxic preconditioning might modulate serum neurotrophin concentrations. Hypoxia was induced for 30 min in 14 healthy young men resulting in a constant blood oxygen saturation of 75%. Hyperinsulinemic euglycemic clamps were performed and serum concentrations of BDNF and NGF were measured at baseline, directly after the intervention, and at the end of the session. Overall, serum BDNF concentrations decreased over time by maximally 35% (P = 0.001) while in contrast NGF concentrations remained unchanged. Acute hypoxia alleviated the decrease of BDNF resulting in higher BDNF concentrations as compared to normoxic control (P < 0.01). Our findings show that acute hypoxia results in significantly higher serum BDNF concentrations pointing to a potential role of BDNF in the underlying mechanism of hypoxic preconditioning. Based on its neuroprotective properties, BDNF may be of high clinical relevance for therapeutic options in ischemic neurovascular diseases.

Feeding ecology of emerald shiners and rainbow smelt in central Lake Erie

To better understand the feeding ecology of two important Laurentian Great Lakes prey species, rainbow smelt Osmerus mordax and emerald shiners Notropis atherinoides, we quantified the diet composition, selectivity, daily ration, and diet overlap of both species in offshore central Lake Erie during May through October 2005, which spanned a period of severe hypolimnetic hypoxia (< 2 mg O 2/L). Rainbow smelt fed upon a variety of prey taxa, including zooplankton, chironomid pupae and larvae, and fish, whereas emerald shiners primarily consumed cladocerans, if available. In turn, diet overlap between rainbow smelt and emerald shiners was low except during September when hypolimnetic hypoxia reduced rainbow smelt access to benthic prey. Rainbow smelt most frequently selected chironomid pupae, while emerald shiners generally selected pupae or large predatory cladocerans ( Leptodora or Bythotrephes). Daily ration and individual consumption by rainbow smelt were 54–68% less during hypoxia than at the same site during stratified pre-hypoxic or mixed post-hypoxic conditions. Although emerald shiner daily ration and individual consumption decreased between pre-hypoxic and hypoxic periods, it continued to decrease during the post-hypoxic period, suggesting that reduced consumption may not have been linked to hypoxic conditions. Ultimately, our findings suggest that emerald shiners are as important regulator of zooplankton abundance in the Great Lakes as rainbow smelt, given their potentially high mass-specific consumption rates, selectivity and diet patterns, and current high abundance.

Gestational stress delays maturation of the hypoxic ventilatory response: an in vivo and in vitro study

Exposure to stress during gestation disrupts CNS development; however, its effects on the respiratory control system are unknown. We tested the hypothesis that exposing dams to a predator odor during gestation disrupts the maturation of the hypoxic ventilatory response (HVR) of newborn rats. From the 9th to the 19th day of pregnancy, females subjected to gestational stress (GS) were placed in a cage containing 35 μl of TMT, a component of fox odor for 20 min. For sham treatment, gestating females were exposed to a strong odor (butyric acid, 105 μl). Controls were undisturbed. Ventilatory activity was measured at post natal days 0, 2 and 4 using plethysmography (in vivo) and "en bloc" brainstem spinal cord preparations (in vitro). Measurements were performed under baseline conditions and hypoxia. In vivo: unlike controls, P4 male pups born to GS dams could not sustain a significant increase in breathing frequency through out the hypoxic period (12% O2, 20 min). This effect of GS was not observed in females. In vitro: at the end of hypoxia (7% O2, 20 min), preparations from GS pups showed a smaller phrenic burst frequency decrease than controls (‐58% vs ‐76%). No sexual dimorphism was observed in vitro. GS delays maturation of the hypoxic ventilatory response. Comparison of in vivo vs in vitro data suggests that GS affects peripheral chemoreceptor development and/or integration of afferent signal in the CNS. Supported by the CIHR.

Development of Resistance of an Organism under Various Conditions of Hypoxic Preconditioning: Role of the Hypoxic Period and Reoxygenation

Single exposure to moderate (10% O(2)) hypobaric, normobaric, and intermittent hypoxia is followed by a preconditioning response of the organism. The mechanisms for immediate adaptation are activated during the hypoxic period. Intermittent reoxygenation not only delays, but even suppresses this process. However, periods of oxygenation during the course of hypoxic training reduce the effect of hypoxia and prevent the possibility for "overdosage" of the adverse stimulus. Hence, they have a regulatory or normalizing role under these conditions. Our results indicate that hypoxitherapy in intermittent hypoxia mode provides optimum conditions for long-term adaptation.

The Impact of Proliferative Potential of Umbilical Cord–Derived Endothelial Progenitor Cells and Hypoxia on Vascular Tubule Formation In Vitro

Revascularization of the damaged tissue is pivotal to tissue repair. Here, by bringing together two in vitro model systems, we have been able to examine (1) the ability of human umbilical vein endothelial cells (HUVEC) containing a complete hierarchy of endothelial progenitors derived from the human umbilical cord to generate vascular tubules within a human stromal niche in vitro and (2) the effects of exposure to low oxygen tensions on endothelial progenitor cell proliferation and tubule formation in vitro. Our results demonstrate that high proliferative potential endothelial colony forming cells (HPP-ECFC) from cultured HUVEC preferentially contribute to vascular tubule formation in vitro and that these progenitor cells are concentrated in the CD34(lo/-) fraction. HUVEC were initially resistant when exposed to hypoxia (1.5% O(2)) for short periods (1-2 days), but sustained chronic hypoxia (4-14 days) inhibited their ability to proliferate. This was reflected by a loss in their ability to form tubules in cocultures of human dermal fibroblasts (hDFs). In contrast, an acute exposure to low oxygen tensions (1.5% O(2) for 24 h) followed by reoxygenation did not adversely affect the capacity of these cells to both proliferate and form vascular tubules in vitro.These studies therefore provide a model system to study the influences of the microenvironmental niche and modification of this niche on vascular tubule formation in vitro from HPP-ECFC.

Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state.

The effect of extreme, prolonged arterial hypoxia on cerebral blood flow, oxygen uptake and intracranial pressure was studied in anesthetized dogs. The experiments were performed along two lines. Both started with a period of hypoxia of about 40 minutes to 2 hours. Thereafter normoxia was restituted in one group and the animals were studied for another 1-2 hours. In the other group with continued hypoxia dopamine was administered. During the hypoxic period the cerebral blood flow decreased mainly as a result of vasoconstriction after an initial marked flow increase. Cerebral oxygen uptake was reduced. Intracranial pressure increased, largely in proportion to blood flow changes, and no indication of important brain edema appeared. In the "recovery" period at normoxia the cerebral oxygen uptake showed an increase during the observation time. The blood flow, initially high, returned to the control level within the observation period. Dopamine infusion during continued hypoxia induced a vasodilatation, with reduction of vascular resistance to the values found at the induction of hypoxia, and with an increase of the cerebral oxygen uptake. An important role of endogenous dopamine in the hypoxic vasodilatation is suggested.

Episodic nocturnal hypoxia and nasal packs

Nasal obstruction influences respiration during sleep and nasal packs may cause obstructive sleep apnoea. In order to investigate this, the perioperative oxygen saturation was monitored for 3 nights with continuous pulse oximetry in 12 patients, who had bilateral nasal packs after septoplasty. A significant increase in the number of nocturnal episodes of hypoxia and a significant prolongation of the mean duration of the individual hypoxic periods were demonstrated during the first and the second post-operative nights. The clinical significance of these results is as yet unknown, but the use of partial nasal packing in septoplasty is advocated. Further investigations of nocturnal oxygen desaturation and design of nasal packs, securing the post-operative nasal airway, are needed.

Sevoflurane and nitrous oxide exert cardioprotective effects against hypoxia-reoxygenation injury in the isolated rat heart

It is unclear whether nitrous oxide (N(2)O) has a protective effect on cardiac function in vitro. In addition, little is known about the cardioprotective effect of anesthesia administered during hypoxia or ischemia. We therefore studied the cardioprotective effects of N(2)O and sevoflurane administered before or during hypoxia in isolated rat hearts. Rat hearts were excised and perfused using the Langendorff technique. For hypoxia-reoxygenation, hearts were made hypoxic (95% N(2), 5% CO(2)) for 45 min and then reoxygenated (95% O(2), 5% CO(2)) for 40 min (control: CT group). Preconditioning was achieved through three cycles of application of 4% sevoflurane (sevo-pre group) or 50% N(2)O (N(2)O-pre group) for 5 min with 5-min washouts in between. Hypoxic conditions were achieved by administering the 4% sevoflurane (sevo-hypo group) or 50% N(2)O (N(2)O-hypo group) during the 45-min hypoxic period. L-type calcium channel currents (I(Ca,L)) were recorded on rabbit myocytes. (1) Both 4% sevoflurane and 50% N(2)O significantly reduced left ventricular developed pressure (LVDP). Sevoflurane also increased left ventricular end-diastolic pressure, though N(2)O did not. (2) The recoveries of LVDP and pressure-rate product (PRP) after hypoxia-reoxygenation were better in the sevo-pre group than in the CT or N(2)O-pre group. (3) Application of either sevoflurane or N(2)O during hypoxia improved recovery of LVDP and PRP, and GOT release was significantly lower than in the CT group. (4) Sevoflurane and N(2)O reduced I(Ca,L) to similar extents. Although sevoflurane administered before or during hypoxia exerts a cardioprotective effect, while N(2)O shows a cardioprotective effect only when administered during hypoxia.