Calcium-independent phospholipase A2-catalyzed plasmalogen hydrolysis in hypoxic human coronary artery endothelial cells

Thrombin stimulation of human coronary artery endothelial cells (HCAEC) results in activation of a membrane-associated, calcium-independent phospholipase A₂ (iPLA₂) that selectively hydrolyzes membrane plasmalogen phospholipids. Rupture of an atherosclerotic plaque and occlusion of the coronary vasculature results in a coronary ischemic event in which HCAEC in the ischemic area would be exposed to dramatic decreases in oxygen tension in addition to thrombin exposure. We exposed HCAEC to hypoxia in the presence or absence of thrombin stimulation and measured iPLA₂ activation, membrane phospholipid hydrolysis, and the accumulation of biologically active phospholipid metabolites. HCAEC exposed to hypoxia, thrombin stimulation, or a combination of the two conditions demonstrated an increase in iPLA₂ activity and an increase in arachidonic acid release from plasmenylcholine. Thrombin stimulation of normoxic HCAEC did not result in an accumulation of choline lysophospholipids, but hypoxia alone and in combination with thrombin stimulation led to a significant accumulation of lysoplasmenylcholine (LPlsCho). We propose that the presence of hypoxia inhibits LPlsCho catabolism, at least in part, as a result of the accumulation of long-chain acylcarnitines. The combination of increased production and decreased catabolism of LPlsCho is necessary for its accumulation. Pretreatment with bromoenol lactone to inhibit iPLA₂ blocked membrane phospholipid hydrolysis and production of membrane phospholipid-derived metabolites. The increase in iPLA₂ activity and the subsequent accumulation of membrane phospholipid-derived metabolites in HCAEC exposed to hypoxia or thrombin stimulation alone, and particularly in combination, have important implications in inflammation and arrhythmogenesis in atherosclerosis/thrombosis and subsequent myocardial ischemia. myocardial ischemia; arrhythmogenesis; thrombosis     

The Optimal Oxygen Equilibrium Curve: A Comparison Between Environmental Hypoxia and Anemia

SYNOPSIS. Internal hypoxia in vertebrates occurs during anemia,when blood oxygen (0₂) carrying capacity is reduced, or duringexposure to environmental hypoxia. In non-altitude adapted vertebrates,exposure to environmental hypoxia results in a change in bloodO₂ affinity which, in some cases is beneficial to tissue O₂delivery. In contrast, the elevation in blood O₂ carrying capacityobserved in almost all vertebrates is always beneficial to tissueO₂ delivery (assuming no large changes in blood viscosity) andmay be more important than changes in blood O₂ affinity in maintainingtissue O₂ delivery. Experimental anemia in vertebrates results in a decrease inblood O₂ affinity which is always beneficial to tissue O₂ delivery.The reduction in affinity is brought about by an increase inthe organic phosphate to hemoglobin ratio (NTP:Hb) within thered cell. In fish NTP:Hb decreases during environmental hypoxiabut increases during anemia indicating that NTP regulation isquite different between these treatments despite the similarityof these treatments at the tissue level.     

Physiological Adaptations of Crayfish to the Hypoxic Environment

SYNOPSIS. Crayfish routinely encounter waters of reduced oxygentension, resulting in a broad array of behavioral and physiologicalresponses. Many animals when faced with this stress will simplyremove themselves from the irritating environment through voluntarymigration. When an animal, either by choice or through physicalconstraints remains in a hypoxic environment it must compensatefor the reduction in O₂ availability. Many crayfish have theability to maintain oxygen consumption independent of waterPo₂ down to some critical level; below this the animal can nolonger maintain normoxic levels of aerobic metabolism. Regulationof oxygen uptake is thought to be due to a hypoxia-induced hyperventilationalong with an increase in hemocyanin O₂ affinity and an improvementin the ability of the respiratory surfaces to transfer O₂. Crayfishexposed to a reduction in water oxygen also show a strong bradycardia,which is compensated for by an increase in stroke volume, resultingin a maintenance of cardiac output. The adaptive advantage ofthis response is uncertain. As water Po₂ drops crayfish havebeen shown to redistribute cardiac output, presumably throughthe action of the cardioarterial valves. Hemolymph is shuntedto the anterior end of the animal, resulting in a greater perfusionof nervous tissue. The animals' ability to detect changes inwater Po₂ appear to result from O₂ sensitive receptors locatedon the gills or in the branchiocardiac veins. The integratedphysiological response toward environmental hypoxia allows thecrayfish to not only deal with the stress but to maintain activity.     

Hypoxia, reactive oxygen, and cell injury

Hypoxia usually decreases the formation of reactive oxygen species by oxidases and by autoxidation of components of cellular electron transfer pathways and of quinoid compounds such as menadione. In the case of menadione reactive oxygen species are liberated to a significant extent only at non-physiologically high oxygen partial pressures (PO2). At physiological and hypoxic PO2 values electron shuttling of menadione in the mitochondrial respiratory chain predominates. In contrast, lipid peroxidation induced by halogenated alkanes, such as carbon tetrachloride, in liver leads to an increase in the formation of reactive oxygen and thus in cell injury under hypoxic conditions. Reactive oxygen species may also be generated during reoxygenation of a previously hypoxic tissue. Based on experiments with isolated hepatocytes a three-zone-model of liver injury due to hypoxia and reoxygenation is presented; 1) a zone where the cells die by hypoxia; 2) a zone where the cells are destroyed upon reoxygenation, presumably mediated by an increase in the cellular ATP content; and 3) a zone where cell injury occurs upon reoxygenation, mediated by reactive oxygen species possibly liberated by xanthine oxidase.     

Reactive oxygen species formation in the transition to hypoxia in skeletal muscle

Many tissues produce reactive oxygen species (ROS) during reoxygenation after hypoxia or ischemia; however, whether ROS are formed during hypoxia is controversial. We tested the hypothesis that ROS are generated in skeletal muscle during exposure to acute hypoxia before reoxygenation. Isolated rat diaphragm strips were loaded with dihydrofluorescein-DA (Hfluor-DA), a probe that is oxidized to fluorescein (Fluor) by intracellular ROS. Changes in fluorescence due to Fluor, NADH, and FAD were measured using a tissue fluorometer. The system had a detection limit of 1 µM H₂O₂ applied to the muscle superfusate. When the superfusion buffer was changed rapidly from 95% O₂ to 0%, 5%, 21%, or 40% O₂, transient elevations in Fluor were observed that were proportional to the rise in NADH fluorescence and inversely proportional to the level of O₂ exposure. This signal could be inhibited completely with 40 µM ebselen, a glutathione peroxidase mimic. After brief hypoxia exposure (10 min) or exposure to brief periods of H₂O₂, the fluorescence signal returned to baseline. Furthermore, tissues loaded with the oxidized form of the probe (Fluor-DA) showed a similar pattern of response that could be inhibited with ebselen. These results suggest that Fluor exists in a partially reversible redox state within the tissue. When Hfluor-loaded tissues were contracted with low-frequency twitches, Fluor emission and NADH emission were significantly elevated in a way that resembled the hypoxia-induced signal. We conclude that in the transition to low intracellular PO₂, a burst of intracellular ROS is formed that may have functional implications regarding skeletal muscle O₂-sensing systems and responses to acute metabolic stress. dihydrofluorescein; tissue fluorometer; ebselen; N-acetylcysteine; rat     

Acute response of the lung mechanics of the rabbit to hypoxia

We measured thechange in total lung resistance(RL) and that in total lungelastance (EL) induced byhypoxia (n = 7) and compared theresults with those by intravenous histamine bolus (n = 5) at three different positiveend-expiratory pressure (PEEP) levels (2, 5, and 8 hPa) in open-chestand vagotomized rabbits. The percent increase ratio ofRL(PIR_R) andEL(PIR_E) was defined as the changein RL andEL, respectively, induced byhypoxia compared with that in the normoxic condition, expressed as apercentage. PIR values for the change inRL andEL induced by bolus injection ofhistamine were also calculated. ThePIR_R andPIR_E induced by hypoxia and byhistamine were positive by a statistically significant amount at everyPEEP level, except for the PIR_Evalue at 8-hPa PEEP in the hypoxic challenge. ThePIR_E-to-PIR_Rratio values in the hypoxic challenge at 2-hPa PEEP were significantlylarger than those in the histamine challenge (hypoxia: 0.91 ± 0.23%; histamine: 0.37 ± 0.065%,P < 0.05). The increasein EL induced by histamine inthe acute phase has been reported to be mainly derived from tissuedistortion secondary to bronchial constriction. Thus our resultssuggest that a part of the increase inEL by hypoxia was originated indifferent parenchymal responses from histamine and imply that thishypoxic response of lung parenchyma is sensitive to the increase inparenchymal tethering at high PEEP levels.

     

Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude cerebral edema

The mechanism by which hypoxia causes high-altitudecerebral edema (HACE) is unknown. Tissue hypoxia triggers angiogenesis, initially by expressing vascular endothelial growth factor (VEGF), which has been shown to increase extracerebral capillary permeability. This study investigated brain VEGF expression in 32 rats exposed toprogressively severe normobaric hypoxia (9-6%O₂) for 0 (control), 3, 6, or 12 h or 1, 2, 3, or 6 days. O₂concentration was adjusted intermittently to the limit of tolerance byactivity and intake, but no attempt was made to detect HACE. Northernblot analysis demonstrated that two molecular bands of transcribed VEGFmRNA (~3.9 and 4.7 kb) were upregulated in cortex and cerebellumafter as little as 3 h of hypoxia, with a threefold increase peaking at12-24 h. Western blot revealed that VEGF protein was increased after 12 h of hypoxia, reaching a maximum in ~2 days. The expression of flt-1 mRNA was enhanced after 3 days of hypoxia. We conclude that VEGF production in hypoxia isconsistent with the hypothesis that angiogenesis may be involved inHACE.

     

Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans

The ventilatorysensitivity to CO₂, in hyperoxia, is increased after an 8-hexposure to hypoxia. The purpose of the present study was to determinewhether this increase arises through an increase in peripheral orcentral chemosensitivity. Ten healthy volunteers each underwent 8-hexposures to 1) isocapnic hypoxia, with end-tidalPO₂ (PET_O2) = 55 Torr and end-tidal PCO₂(PET_CO2) = eucapnia; 2)poikilocapnic hypoxia, with PET_O2 = 55 Torr and PET_CO2 = uncontrolled;and 3) air-breathing control. The ventilatory response toCO₂ was measured before and after each exposure with theuse of a multifrequency binary sequence with two levels of PET_CO2: 1.5 and 10 Torr above the normalresting value. PET_O2 was held at 250 Torr.The peripheral (Gp) and the central (Gc) sensitivities were calculatedby fitting the ventilatory data to a two-compartment model. There wereincreases in combined Gp + Gc (26%, P < 0.05),Gp (33%, P < 0.01), and Gc (23%, P = not significant) after exposure to hypoxia. There were no significant differences between isocapnic and poikilocapnic hypoxia. We conclude that sustained hypoxia induces a significant increase inchemosensitivity to CO₂ within the peripheral chemoreflex.

     

Role of carotid body activity responsible for hypoxic ventilatory decline in awake humans

Long, W. Q., G. G. Giesbrecht, and N. R. Anthonisen. Ventilatory response to moderate hypoxia in awakechemodenervated cats. J. Appl. Physiol. 74(2): 805-810, 1993.In humans and cats the ventilatory response to 30 min ofmoderate hypoxia (arterial PO₂ 40-55Torr) is biphasic: ventilation increases sharply for the first 5 minand then declines. In humans there is evidence that the decline isdependent on the initial increase. We therefore examined ventilatoryresponses to moderate isocapnic hypoxia in awake cats with and withoutcarotid body denervation. Cats underwent denervation or a shamoperation. Then they were studied in a Drorbaugh-Fenn plethysmographwhile ventilation, arterial PO₂, and end-tidal PO₂ and PCO₂ weremeasured. Three sham-operated and four denervated cats were studiedwith room air as the control. Sham animals demonstrated a biphasicresponse: ventilation rose to 211% of control at 5 min and fell to114% of control at 25 min. Denervated animals showed neither theinitial increase nor the subsequent decrease in ventilation. Threesham-operated and three denervated cats were studied with 2%CO₂ added to the inspirate. Results were similar: intactcats showed a biphasic response to hypoxia, whereas denervated catsshowed neither an increase nor a decrease in ventilation. Preliminaryexperiments showed that hypoxia was not associated with changes inCO₂ output or systemic blood pressure in either denervatedor intact animals. We conclude that depression of ventilation does notoccur in awake denervated cats in response to moderate hypoxiaand that the decline in ventilation that occurs in intact cats is insome way dependent on peripheral chemoreceptor output.

     

Mild sustained and intermittent hypoxia induce apoptosis in PC-12 cells via different mechanisms

Episodic hypoxia, a characteristic feature of obstructive sleep apnea, induces cellular changes and apoptosis in brain regions associated with neurocognitive function. To investigate whether mild, intermittent hypoxia would induce more extensive neuronal damage than would a similar degree of sustained hypoxia, rat pheochromocytoma PC-12 neuronal cells were subjected to either sustained (5% O₂) or intermittent (alternating 5% O₂ 35 min, 21% O₂ 25 min) hypoxia for 2 or 4 days. Quantitative assessment of apoptosis showed that while mild sustained hypoxia did not significantly increase cell apoptosis at 2 days (1.31 ± 0.29-fold, n = 8; P = NS), a significant increase in apoptosis occurred after 4 days (2.25 ± 0.4-fold, n = 8; P < 0.002), without increased caspase activation. Furthermore, caspase inhibition with the general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) did not modify sustained hypoxia-induced apoptosis. In contrast, mild, intermittent hypoxia induced significant increases in apoptosis at 2 days (3.72 ± 1.43-fold, n = 8; P < 0.03) and at 4 days (4.57 ± 0.82-fold, n = 8; P < 0.001) that was associated with enhanced caspase activity and attenuated by Z-VAD-FMK pretreatment. We conclude that intermittent hypoxia induces an earlier and more extensive apoptotic response than sustained hypoxia and that this response is at least partially dependent on caspase-mediated pathways. In contrast, caspases do not seem to play a role in sustained hypoxia-induced apoptosis. These findings suggest that different signaling pathways are involved in sustained and intermittent hypoxia-induced cell injury and may contribute to the understanding of differential brain susceptibility to sustained and intermittent hypoxia. episodic hypoxia; neuronal cell death; caspase; hypoxic adaptation     

Physiological Responses to Oxygen Depletion in Intertidal Animals

SYNOPSIS. Aquatic habitats, especially those of the intertidal,are subject to massive fluctuation of O₂ level including periodsof both extreme hypoxia and hyperoxia. Most animals have someability to regulate oxygen consumption during oxygen depletion,although the critical oxygen level above which compensationis possible varies complexly with many external and internalfactors. Mechanisms of detection of, and compensation for, hypoxicexposure are examined, in both the short and long-term. Thetime courses of behavioral, ventilatory and circulatory responsesto hypoxia are outlined and the limitations of their role inmaintenance of aerobic metabolism are discussed. The role ofadjustment of O₂ binding properties of respiratory pigmentsin maintenance of O₂ consumption in hypoxia is also explored.Finally the role of anaerobic energy production is briefly outlined.     

Root Respiration and Carbohydrate Status of Two Wheat Genotypes in Response to Hypoxia

To investigate root respiration and carbohydrate status in relationto waterlogging or hypoxia tolerance, root respiration rateand concentrations of soluble sugars in leaves and roots weredetermined for two wheat (Triticum aestivum L.) genotypes differingin waterlogging-tolerance under hypoxia (5% O₂) and subsequentresumption of full aeration. Root and shoot growth were reducedby hypoxia to a larger extent for waterlogging-sensitive Coker9835. Root respiration or oxygen consumption rate declined withhypoxia, but recovered after 7 d of resumption of aeration.Respiration rate was greater for sensitive Coker 9835 than fortolerant Jackson within 8 d after hypoxia. The concentrationsof sucrose, glucose and fructose decreased in leaves for bothgenotypes under hypoxia. The concentration of these sugars inroots, however, increased under hypoxia, to a greater degreefor Jackson. An increase in the ratio of root sugar concentrationto shoot sugar concentration was found for Jackson under hypoxicconditions, suggesting that a large amount of carbohydrate waspartitioned to roots under hypoxia. The results indicated thatroot carbohydrate supply was not a limiting factor for rootgrowth and respiration under hypoxia. Plant tolerance to waterloggingof hypoxia appeared to be associated with low root respirationor oxygen consumption rate and high sugar accumulation underhypoxic conditions.Copyright 1995, 1999 Academic Press Oxygen consumption rate, sugar accumulation, Triticum aestivum L., waterlogging tolerance     

Egg-Mass Size and Cell Size: Effects of Temperature on Oxygen Distribution

Two processes strongly influence the distribution of oxygenwithin egg masses and cells: the supply of oxygen by diffusionand the consumption of oxygen by embryos and mitochondria. Theseprocesses are differentially sensitive to temperature. The diffusioncoefficient of oxygen depends only weakly on temperature, havinga Q₁₀ of approximately 1.4. In contrast, the consumption ofoxygen depends strongly on temperature, having a Q₁₀ between1.5 and 4.0. Thus, at higher temperatures, the ratio of oxygensupply to demand decreases. I show, by extending a model ofoxygen distribution within metabolizing spheres, that maximalegg-mass sizes and cell sizes are predicted to be smaller athigher temperatures. For egg masses, definitive data are notyet available. For ectothermic cells, this prediction appearsto be supported; cells from a variety of ectothermic organisms,unicellular and multicellular, are smaller when the cells areproduced at warmer temperatures. Establishing a specific connectionbetween this pattern and oxygen distributions requires demonstrationof (1) oxygen concentration gradients within metabolizing spheresand (2) central oxygen concentrations low enough to affect function.Egg masses from a variety of taxa show steep oxygen concentrationgradients and often are severely hypoxic or anoxic in centrallocations. Severe hypoxia appears capable of retarding developmentor killing embryos. Similar kinds of data for ectothermic cellshave not yet been collected, but the literature on oxygen gradientswithin mammalian cells suggests that intracellular gradientsmay be important.     

Effect of hypoxia on abdominal motor unit activities in spontaneously breathing cats

Mateika, J. H., E. Essif, and R. F. Fregosi. Effect ofhypoxia on abdominal motor unit activities in spontaneously breathingcats. J. Appl. Physiol. 81(6):2428-2435, 1996.These experiments were designed to examine thebehavior of external oblique motor units in spontaneously breathingcats during hypoxia and to estimate the contribution of recruitment andrate coding to changes in the integrated external obliqueelectromyogram (iEMG). Motor unit activities in the external obliquemuscle were identified while the cats expired against a positiveend-expiratory pressure (PEEP) of 1-2.5cmH₂O. After localization of unitactivity, PEEP was removed, and recordings were made continuously for3-4 min during hyperoxia, normoxia, and hypoxia. A total of 35 single motor unit activities were recorded from 10 cats. At each level of fractional concentration of end-tidalO₂, the motor unit activity wascharacterized by an abrupt increase in mean discharge frequency, at~30% of expiratory time, which then continued to increase gradually or remained constant before declining abruptly at the end ofexpiration. The transition from hyperoxia to normoxia and hypoxia wasaccompanied by an increase in the number of active motor units (16 of35, 20 of 35, and 29 of 35, respectively) and by an increase in the mean discharge frequency of those units active during hyperoxia. Thechanges in motor unit activity recorded during hypoxia were accompaniedby a significant increase in the average peak amplitude of theabdominal iEMG. Linear regression analysis revealed that motor unitrate coding was responsible for close to 60% of the increase in peakiEMG amplitude. The changes in abdominal motor unit activity and theexternal oblique iEMG that occurred during hypoxia were abolished ifthe arterial PCO₂ was allowed tofall. We conclude that external oblique motor units are activated during the latter two-thirds of expiration and that rate coding andrecruitment contribute almost equally to the increase in expiratory muscle activity that occurs with hypoxia. In addition, the excitation of abdominal motor units during hypoxia is critically dependent onchanges in CO₂ and/ortidal volume.

     

Ontogeny of Cardiac and Ventilatory Function in the Crayfish Procambarus clarkii

SYNOPSIS. Ontog eny of cardiac and ventilatory function wasinvestigated in the direct developing crayfish Procambarus clarkiito determine basic developmental patterns and to evaluate diffusionaland convective gas exchange. Animals were exposed to water rangingin Po₂ from 150 to less than 10 mmHg. Ontogeny of cardiac functionfollows a pattern unlike that observed in other developing organisms.Heart rate (f_H) decreases from the mid-point of embryonic developmentuntil hatching, and the decrease in f_H is accompanied by a concomitantloss in cardiac and ventilatory sensitivity to hypoxia. Duringlarval development however, f_H increases until a juvenile stageis reached. Heart rate then decreases again as the animal increasesin mass. Cardiac and ventilatory responses to hypoxia are restoredby the third larval instar. Ventilatory function is initiatedwithin hours of hatching. Scaphognathite movement (f_sc), whichis initially uncoordinated, does not result in appreciable movementof water, but functional pumping is achieved within hours ofhatching. Animals do not exhibit an adult-like response to hypoxicexposure until at least the third larval instar. The ontogenyof both cardiac and ventilatory function indicates that thedirect developing crayfish is not physiologically mature untilan early juvenile stage. The drop in embryonic JFH and lossof hypoxic sensitivity late in development may indicate thatoxygen requirements of embryos exceed the capacity of egg membranescapacity (surface area) to supply oxygen by diffusion.     

From critters to cancers: bridging comparative and clinical research on oxygen sensing, HIF signaling, and adaptations towards hypoxia

The objective of this symposium at the First International Congressof Respiratory Biology (ICRB) was to enhance communication betweencomparative biologists and cancer researchers working on O₂sensing via the HIF pathway. Representatives from both campscame together on August 13–16, 2006, in Bonn, Germany,to discuss molecular adaptations that occur after cells havebeen challenged by a reduced (hypoxia) or completely absent(anoxia) supply of oxygen. This brief "critters-to-cancer" surveydiscusses current projects and new directions aimed at improvingunderstanding of hypoxic signaling and developing therapeuticinterventions.     

Lactate efflux from exercising human skeletal muscle: role of intracellular PO2

It remainscontroversial whether lactate formation during progressive dynamicexercise from submaximal to maximal effort is due to muscle hypoxia. Tostudy this question, we used direct measures of arterial and femoralvenous lactate concentration, a thermodilution blood flow technique,phosphorus magnetic resonance spectroscopy (MRS), and myoglobin (Mb)saturation measured by ¹H nuclearMRS in six trained subjects performing single-leg quadriceps exercise.We calculated net lactate efflux from the muscle and intracellularPO₂ with subjects breathing room airand 12% O₂. Data were obtained at50, 75, 90, and 100% of quadriceps maximalO₂ consumption at each fraction ofinspired O₂. Mb saturation wassignificantly lower in hypoxia than in normoxia [40 ± 3 vs. 49 ± 3% (SE)] throughout incremental exercise to maximalwork rate. With the assumption of aPO₂ at which 50% of Mb-binding sitesare bound with O₂ of 3.2 Torr,Mb-associated PO₂ averaged 3.1 ± 0.3 and 2.3 ± 0.2 Torr in normoxia and hypoxia, respectively. Netblood lactate efflux was unrelated to intracellular PO₂ across the range of incrementalexercise to maximum (r = 0.03 and 0.07 in normoxia and hypoxia, respectively) but linearly related toO₂ consumption(r = 0.97 and 0.99 in normoxia andhypoxia, respectively) with a greater slope in 12%O₂. Net lactate efflux was alsolinearly related to intracellular pH(r = 0.94 and 0.98 in normoxia andhypoxia, respectively). These data suggest that with increasing workrate, at a given fraction of inspiredO₂, lactate efflux is unrelated tomuscle cytoplasmic PO₂, yet theefflux is higher in hypoxia. Catecholamine values from comparablestudies are included and indicate that lactate efflux in hypoxia may bedue to systemic rather than intracellular hypoxia.

     

Effect of hypoxia on respiratory system impedance in dogs

Simon, B. A., P. B. Zanaboni, and D. P. Nyhan. Effectof hypoxia on respiratory system impedance in dogs. J. Appl. Physiol. 83(2): 451-458, 1997.The effects of hypoxia on lung and airwaymechanics remain controversial, possibly because of the confoundingeffects of competing reflexes caused by systemic hypoxemia. We comparedthe effects of systemic hypoxemia with those of unilateral alveolarhypoxia (with systemic normoxemia) on unilateral respiratory systemimpedance (Z) in intact, anesthetized dogs. Independent lungventilation was obtained with a Kottmeier endobronchial tube.Individual left and right respiratory system Z was measured duringsinusoidal forcing with 45 ml of volume at frequencies of 0.2-2.1Hz during control [100% inspiredO₂ fraction(FI_O2)], systemichypoxemia (10% FI_O2), andunilateral alveolar hypoxia (0%FI_O2 to left lung, 100%FI_O2 to right lung). Duringsystemic hypoxemia, there was a mean Z magnitude increase of 18%. Thischange was entirely attributable to a decrease in the imaginarycomponent of Z; there was no change in the real component of Z. Administration of atropine (0.2 mg/kg) did not block the increase in Zwith systemic hypoxemia. In contrast, there was no change in Z in thelung subjected to unilateral alveolar hypoxia. We conclude thatalveolar hypoxia has no direct effect on lung mechanical properties inintact dogs. In contrast, systemic hypoxemia does increase lungimpedance, apparently through a noncholinergic mechanism.

     

Changes in respiratory control during and after 48h of isocapnic and poikilocapnic hypoxia in humans

Ventilatory acclimatization tohypoxia is associated with an increase in ventilation under conditionsof acute hyperoxia(E_hyperoxia) and an increase in acute hypoxic ventilatory response (AHVR). Thisstudy compares 48-h exposures to isocapnic hypoxia( protocol I) with 48-hexposures to poikilocapnic hypoxia ( protocolP) in 10 subjects to assess the importance ofhypocapnic alkalosis in generating the changes observed in ventilatoryacclimatization to hypoxia. During both hypoxic exposures,end-tidal PO₂ was maintained at60 Torr, with end-tidal PCO₂ held at the subject's prehypoxic level( protocol I) or uncontrolled( protocol P).E_hyperoxiaand AHVR were assessed regularly throughout the exposures.E_hyperoxia(P < 0.001, ANOVA) and AHVR(P < 0.001) increased during thehypoxic exposures, with no significant differences betweenprotocols I andP. The increase inE_hyperoxiawas associated with an increase in slope of theventilation-end-tidal PCO₂ response(P < 0.001) with no significantchange in intercept. These results suggest that changes in respiratorycontrol early in ventilatory acclimatization to hypoxiaresult from the effects of hypoxia per se and not the alkalosisnormally accompanying hypoxia.

     

Changes in leaf gas exchange, water relations, biomass production and solute accumulation in Phragmites australis under hypoxic conditions

The physiological responses to hypoxic stress were studied in the common reed, Phragmites australis (Cav.) Trin. ex Steudel. Growth, leaf gas exchange, water (and ion) relations and osmotic adjustment were determined in hydroponically grown plants exposed to 10, 20 and 30 days of oxygen deficiency. The highest growth of reed seedlings was found in normoxic (aerobic) conditions. Treatment effects on biomass production were relatively consistent within each harvest. Leaf water potential and osmotic potential declined significantly as hypoxia periods increased. However, leaf turgor pressure showed a consistent pattern of increase, suggesting that reed plants adjusted their water status by osmotic adjustment in response to root hypoxia. After 20 and 30 days in the low oxygen treatment, net CO₂ assimilation and stomatal conductance were positively associated and the former variable also had a strong positive relationship with transpiration. Short-term hypoxic stress had a slight effect on the ionic status (K⁺, Ca²⁺ and Mg²⁺) of reed plants. In contrast, soluble sugar concentrations increased more under hypoxic conditions as compared to normoxia. These findings indicate that hypoxia slightly affected the physiological behavior of reed plants.