Acute short-term hyperoxia followed by mild hypoxia does not increase EPO production: resolving the "normobaric oxygen paradox"

Recent findings suggest that besides renal tissue hypoxia, relative decrements in tissue oxygenation, using a transition of the breathing mixture from hyperoxic to normoxic, can also stimulate erythropoietin (EPO) production. To further clarify the importance of the relative change in tissue oxygenation on plasma EPO concentration [EPO], we investigated the effect of a consecutive hyperoxic and hypoxic breathing intervention. Eighteen healthy male subjects were assigned to either IHH (N = 10) or CON (N = 8) group. The IHH group breathed pure oxygen (F_iO₂ ~ 1.0) for 1 h, followed by a 1-h period of breathing a hypoxic gas mixture (F_iO₂ ~ 0.15). The CON group breathed a normoxic gas mixture (F_iO₂ ~ 0.21) for the same duration (2 h). Blood samples were taken just before, after 60 min, and immediately after the 2-h exposure period. Thereafter, samples were taken at 3, 5, 8, 24, 32, and 48 h after the exposure. During the breathing interventions, subjects remained in supine position. There were significant increases in absolute [EPO] within groups at 8 and 32 h in the CON and at 32 h only in the IHH group. No significant differences in absolute [EPO] were observed between groups following the intervention. Relative (∆[EPO]) levels were significantly lower in the IHH than in the CON group, 5 and 8 h following exposure. The tested protocol of consecutive hyperoxic-hypoxic gas mixture breathing did not induce [EPO] synthesis stimulation. Moreover, the transient attenuation in ∆[EPO] in the IHH group was most likely due to a hyperoxic suppression. Hence, our findings provide further evidence against the “normobaric O₂ paradox” theory.     

Increased erythropoietin concentration after repeated apneas in humans

Hypoxia-induced increases in red blood cell production have been found in both altitude-adapted populations and acclimatized lowlanders. This process is mediated by erythropoietin (EPO) released mainly by the hypoxic kidney. We have previously observed high hemoglobin concentrations in elite breath-hold divers and our aim was to investigate whether apnea-induced hypoxia could increase EPO concentration. Ten healthy volunteers performed 15 maximal duration apneas, divided into three series of five apneas, each series separated by 10 min of rest. Apneas within series were separated by 2 min and preceded by 1 min of hyperventilation to increase apnea duration and arterial oxygen desaturation. When EPO concentration after serial apneas was compared to baseline values, an average maximum increase of 24% was found (P < 0.01). No changes in EPO concentration were observed during a control day without apnea, eliminating possible effects of a diurnal rhythm or blood loss. We therefore conclude that serial apneas increase circulating EPO concentration in humans.     

Influence of oxygen and carbogen breathing on renal oxygenation measured by T2*‐weighted imaging at 3.0 T

The aim of the study was to assess the influence of carbogen (95% O₂, 5% CO₂) or pure oxygen breathing on renal oxygenation measured by blood oxygenation level dependent (BOLD) magnetic resonance imaging at 3.0 T. Seven healthy young volunteers (median age 25, range 23–35 years) participated in the study. A T2*‐weighted fat‐saturated spoiled gradient‐echo sequence was implemented on a 3.0 T whole‐body imager (TE/TR = 27.9 ms/49 ms, excitation angle 20°) with an acquisition time of approximately 5.3 s. A total of 100 images were acquired during 22 min. A block design was applied for gas administration: 4 min room air, 4 min carbogen/oxygen, 4 min room air, 4 min carbogen/oxygen and 6 min room air. A compartment model was fitted to the data sets accounting for time‐dependent increase/decrease of renal oxygenation as well as baseline changes of the scanner. T2*‐weighted images showed good image quality without notable artefacts or distortions. Mean relative signal increase due to carbogen breathing was 2.73% (95% confidence interval: 1.34–5.54) in the right kidney and 3.76% (1.53–9.20) in the left kidney, while oxygen breathing led to a signal enhancement of 3.20% (2.57–3.98) in the right kidney and 3.16% (1.83–5.45) in the left kidney. No statistical difference was found between carbogen and oxygen breathing or between the oxygenation of the right and the left kidney. A significant difference was found in the characteristic time constant for the signal increase with a faster saturation taking place for oxygen breathing. Renal tissue oxygenation is clearly influenced by carbogen or oxygen breathing. The changes can be assessed by T2*‐weighted MRI at high field strengths. The effects are in the expected range for the BOLD effect of 3–4% at 3.0 T. The proposed technique might be interesting for the assessment of renal tissue oxygenation and its regulation in patients with kidney diseases. Copyright © 2009 John Wiley & Sons, Ltd.     

Oxygen breathing may be a cheaper and safer alternative to exogenous erythropoietin (EPO)

Erythropoietin (EPO) is a glycoprotein hormone produced by renal tissue in response to hypoxia; EPO functions as a cytokine to precursor cells produced by the bone marrow, stimulating red blood cell production. Erythropoiesis stimulating agents (ESAs) are manufactured molecules designed to mimic the ability of endogenous EPO to bind to EPO receptors and increase red blood cell production. To achieve desired dosing schedules and avoid the need for blood transfusions, oncologists have become increasingly reliant on ESAs to counter the anemia often experienced during chemotherapy. In recent years, significant concerns have been raised about the safety of ESAs, including the possibility of increased cardiovascular events and even increased tumor growth and accelerated mortality in cancer patients. ESAs also contribute significantly to the expense of chemotherapy, rendering them unavailable to some patients and available to others only upon achieving insurance-mandated levels of anemia. A recently discovered "normobaric oxygen paradox" demonstrates that renal tissue can be stimulated to increase EPO production via a simple pattern of oxygen breathing at normal atmospheric pressures. This leads directly to the hypothesis that oxygen breathing may provide chemotherapy patients with a convenient and inexpensive alternative to ESAs. Stimulating endogenous EPO production eliminates the small risk of immune system reaction associated with ESAs. Further, the endogenous physiological EPO doses provided by this method may be safer, in terms of cancer mortality, than the exogenous pharmacological doses inherent in ESA administration. A single patient test case is presented to support the hypothesis that normobaric oxygen breathing can be an effective replacement for ESAs in treating chemotherapy-induced anemia. In this case, a stage III breast cancer patient undergoing dose-dense AC+T chemotherapy obtained a clear response equivalent to ESA treatment by using a pattern of simple oxygen breathing.     

Dose-dependent effect of angiotensin II on human erythropoietin production

Current evidence suggests that angiotensin II may be involved in the regulation of renal erythropoietin (EPO) production. The present study assessed the role of angiotensin II (A II) in different doses in the control of EPO production in humans. In a parallel, randomized, placebo-controlled open design, 60 healthy male volunteers received a 6-h intravenous infusion of: placebo (placebo, electrolyte solution), a pressor dose of A II (1-3 microg/min; A II press), a combination of a pressor dose of A II and the selective AT1-receptor blocker losartan, 50 mg (A II press + L), a subpressor dose of A II (0.0375-0.15 microg/min; A II subpress) and a combination of a subpressor dose of A II and losartan (A II subpress + L). A II press treatment resulted in a significant increase of the maximum EPO concentration (CmaxEPO, 41% higher versus placebo) and the amount of EPO produced in 24 h (AUCEPO(0-24 h), 61% larger versus placebo), A II subpress treatment increased CmaxEPO (35% higher versus placebo) and AUC(EPO)(0-24 h) (34% larger versus placebo). A II press + L and A II subpress + L treatments did not significantly increase CmaxEPO and AUCEPO(0-24 h) compared to placebo. A II affects EPO production in a dose-dependent manner. The signal seems to be mediated via AT1-receptors. A II appears to be one modulator EPO production in humans.     

Acute normobaric hyperoxia transiently attenuates plasma erythropoietin concentration in healthy males: evidence against the 'normobaric oxygen paradox' theory

Aim: The purpose of the present study was to evaluate the ‘normobaric oxygen paradox’ theory by investigating the effect of a 2‐h normobaric O₂ exposure on the concentration of plasma erythropoietin (EPO). Methods: Ten healthy males were studied twice in a single‐blinded counterbalanced crossover study protocol. On one occasion they breathed air (NOR) and on the other 100% normobaric O₂ (HYPER). Blood samples were collected Pre, Mid and Post exposure; and thereafter, 3, 5, 8, 24, 32, 48, 72 and 96 h, and 1 and 2 weeks after the exposure to determine EPO concentration. Results: The concentration of plasma erythropoietin increased markedly 8 and 32 h after the NOR exposure (approx. 58% and approx. 52%, respectively, P ≤ 0.05) as a consequence of its natural diurnal variation. Conversely, the O₂ breathing was followed by approx. 36% decrement of EPO 3 h after the exposure (P ≤ 0.05). Moreover, EPO concentration was significantly lower in HYPER than in the NOR condition 3, 5 and 8 h after the breathing intervention (P ≤ 0.05). Conclusion: In contrast to the ‘normobaric oxygen paradox’ theory, the present results indicate that a short period of normobaric O₂ breathing does not increase the EPO concentration in aerobically fit healthy males. Increased O₂ tension suppresses the EPO concentration 3 and 5 h after the exposure; thereafter EPO seems to change in a manner consistent with natural diurnal variation.     

The Relationship Between N-acetylcysteine, Hyperbaric Oxygen, and Inflammation in a Rat Model of Acetaminophen-induced Nephrotoxicity

An overdose of acetaminophen (APAP) produces acute tubular necrosis. The aim of this study was to observe the effects of hyperbaric oxygen (HBO) only and combined with N-acetylcysteine (NAC) on inflammatory cytokines in kidney. Thirty-two male Sprague–Dawley rats were divided into four groups: sham, control (APAP), NAC, and NAC?+?HBO. In the APAP, NAC, and NAC?+?HBO groups, renal injury was induced by oral administration of 1 g/kg APAP. The NAC group received NAC (100 mg/kg/day). NAC?+?HBO group received NAC (100 mg/kg/day) intraperitoneally and HBO underwent at 2.8 ATA pressure with 100 % oxygen inhalation for 90 min every 12 h for 5 days. Rats in the sham group received distilled water only by gastric tube. All animals were killed on 6 days after APAP or distilled water administration. Creatinine, urea, neopterin, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 levels were measured in sera. There was a significant increase in serum creatinine and urea levels in the control group compared to the sham group (in both, p?=?0.001). NAC and NAC?+?HBO significantly decreased serum neopterin, TNF-α, and IL-6 levels compared to control group. APAP administration caused tubular necrosis in the renal. NAC and NAC?+?HBO treatments significantly reduced APAP-induced renal damage. The results of this study showed that renal dysfunction in APAP toxicity was attenuated by the use of HBO and NAC treatments. The combination of NAC and HBO treatments might be recommended as an effective treatment modality for APAP-induced nephrotoxicity.     

Human erythropoietin response to hypocapnic hypoxia,normocapnic hypoxia,and hypocapnic normoxia

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO₂ to the hypoxic gas. On separate days, eight healthy male subjects were exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVAP = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other experiments were corrected for these spontaneous variations in each individual. At 2 h after ending hypocapnic hypoxia (10% O₂ in nitrogen), mean serum-EPO increased by 28% [baseline 8.00 (SEM 0.84) U · 1⁻¹, post-hypoxia 10.24 (SEM 0.95) U · 1⁻¹, P = 0.005]. Normocapnic hypoxia was produced by the addition of CO₂ (10% Co₂ with 10% O₂) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVAP > 0.05). Hypocapnic normoxia, produced by hyperventilation of room air, elicited a normoxic increase in the haemoglobin oxygen affinity without changing serum-EPO. Among the measured blood gas and acid-base parameters, only the partial pressures of oxygen in arterial blood during hypocapnic hypoxia were related to the peak values of serum-EPO (r = −0.81,P = 0.01). The present human EPO responses to hypoxia were lower than those which have previously been reported in rodents and humans. In contrast with the earlier rodent studies, it was found that human EPO production could not be triggered by short-term increases in pH and haemoglobin oxygen affinity per se, and the human EPO response to hypoxia could be suppressed by concomitant normocapnia without acidosis.     

The effects of substrate utilization,manipulated by caffeine,on post-exercise oxygen consumption in untrained female subjects

Summary The effect of substrate utilization manipulated by caffeine on post-exercise oxygen consumption was investigated in five untrained females (age=21±1.5 years), following 90 min of treadmill walking at 55% maximal oxygen consumption. Each subject participated in the two trials (control and experimental) within 2 weeks of each other. Immediately following the measurement of resting oxygen consumption, subjects consumed one of the two test beverages 60 min prior to exercise: 5 mg of caffeine per kg of bodyweight in 200 ml of orange juice (CA) or 200 ml of orange juice (C). Assignment of CA and C was made in a random, double blind fashion. Immediately prior to the exercise phase (0 min) resting oxygen consumption was again measured. Following exercise, subjects returned to the same pre-exercise sitting position where respiratory data was collected over 1 h. No significant differences were found in resting oxygen consumption and respiratory exchange ratio (R) prior to caffeine ingestion (−60 min). One hour after caffeine ingestion (0 min) oxygen consumption and free fatty acid (FFA) levels increased significantly compared to C. During and 1 h following exercise, oxygen consumption and FFA levels were significantly greater, with R values being significantly lower in CA compared to C. These findings provide further evidence that metabolic substrate is somehow implicated in elevating oxygen consumption following exercise cessation.     

Prophylaxis with α-lipoic acid against lipopolysaccharide-induced brain injury in rats

Introduction  Lipopolysaccharide (LPS) stimulates the synthesis and release of reactive oxygen species that play an important role in the pathogenesis of tissue injuries. In this study the effect of early administration of the antioxidant α-lipoic acid (α-LA) on brain lipid peroxidation, brain hydrogen peroxide (H₂O₂) concentration, and brain total sulfhydryl group (-SH group) content was evaluated in rats with endotoxic shock induced by administration of LPS (Escherichia coli 026:B6, 30 mg/kg i.v.) Materials and Methods  Rats were treated intravenously with normal saline or α-LA (60 mg/kg) 30 min after LPS injection. After 5 h of observation, the animals were killed and their brains were isolated for the measurements. Results  Injection of LPS alone resulted in the development of shock and oxidative stress, the latter indicated by a significant increase in brain concentrations of thiobarbituric acid-reacting substances (TBARS) and H₂O₂ and a decrease in total brain -SH group content. Administration of α-LA after the LPS challenge resulted in an increase in total -SH group content and a decrease in TBARS and H₂O₂ concentration in the brain tissue compared with the LPS group. Conclusion  The results indicate that α-LA treatment effectively protected the brain tissue against endotoxin-induced oxidative stress. Administration of LA could be a useful adjunct to clinical application in the management of septic shock.     

Respiratory response to systemic inhibition of the Na/H exchanger type 3 in intact rats

The Na⁺/H⁺ exchangers (NHEs) are a family of antiporters involved in the maintenance of neural steady-state intracellular pH. The NHE3 seems to be the predominant subtype in central chemosensitive cells. We aimed to analyze the effect of a selective NHE3 inhibition on the respiratory pattern in spontaneously breathing rats with intact vagi. Rats were intravenously infused for 10 min with the selective NHE3 inhibitor AVE1599 (Aventis Pharma Deustchland, 0.5 and 2 mg/kg) or with phosphate buffer. Whole-body plethysmography was used to monitor breathing pattern before, during, and up to 30 min after the drug infusion. Immunohistochemistry for the c-Fos protein was performed in the animal brains and c-Fos-positive cells were counted along the brainstem. Selective NHE3 inhibition induced a significant increase in the respiratory frequency and in the number of c-Fos immunopositive cells in the lateral parabrachial nucleus, the pre-Bötzinger complex and a rostral extension of the retrotrapezoid nucleus/parapyramidal region (p < 0.05, ANOVA). We conclude that systemic administration of AVE1599 increases respiratory frequency and activates ponto-medullary areas implicated in the central control of breathing and chemoreception.     

Hyperoxia-induced alterations in cardiovascular function and autonomic control during return to normoxic breathing

Hyperoxia causes hemodynamic alterations. We hypothesized that cardiovascular and autonomic control changes last beyond the end of hyperoxic period into normoxia. Ten healthy volunteers were randomized to breathe either medical air or 100% oxygen for 45 min in a double-blind study design. Measurements were performed before (baseline) and during gas exposure, and then 10, 30, 60, and 90 min after gas exposure. Hemodynamic changes were studied by Doppler echocardiography. Changes in cardiac and vasomotor autonomic control were evaluated through changes in spectral power of heart rate variability and blood pressure variability. Cardiac baroreflex sensitivity was assessed by the sequence method. Hyperoxia significantly decreased heart rate and increased the high frequency power of heart rate variability, suggesting a chemoreflex increase in vagal activity since the slope of cardiac baroreflex was significantly decreased during hyperoxia. Hyperoxia increased significantly the systemic vascular resistances and decreased the low frequency power of blood pressure variability, suggesting that hyperoxic vasoconstriction was not supported by an increase in vascular sympathetic stimulation. These changes lasted for 10 min after hyperoxia (p < 0.05). After the end of hyperoxic exposure, the shift of the power spectral distribution of heart rate variability toward a pattern of increased cardiac sympathetic activity lasted for 30 min (p < 0.05), reflecting a resuming of baseline autonomic balance. Cardiac output and stroke volume were significantly decreased during hyperoxia and returned to baseline values (10 min) later than heart rate. In conclusion, hyperoxia effects continue during return to normoxic breathing, but cardiac and vascular parameters followed different time courses of recovery.     

The acute effects of ondansetron on the electrocardiogram in clinically normal dogs

This study was performed to determine the acute effects of a single intravenous dose of ondansetron on the electrocardiogram of dogs. Eight adult crossbreed dogs were used in this study. The electrocardiogram recording was obtained before the infusion of ondansetron and repeated at 5, 30, 60, and 120 min after treatment. The ECG measurements of heart rate, PR interval, QRS interval, ST segment, T-wave amplitude, and QT interval were taken from lead II. The JT interval was calculated as the QT interval minus the QRS interval. Rate-corrected QT and JT intervals (QTc and JTc) were obtained by using two formulas QTc = QT/³√R-R interval and JTc = JT/³√R-R interval. In comparison to the baseline values, mean heart rate significantly decreased at 5, 30, and 60 min after administration of intravenous ondansetron. There was significant prolongation of QT, QTc, and JT intervals at 30 and 60 min after infusion of drug. T-waves showed significant changes in its direction and amplitude at 60 and 120 min after treatment compared to the baseline values. In conclusion, ondansetron at standard dosages apparently causes ECG changes in healthy dogs. These include marked QT interval prolongation and reduction in heart rate. Although in current experiment, we did not observe serious arrhythmias in this group of dogs, it does not exclude the possibility of ventricular arrhythmias in prolonged use after reaching a certain cumulative dose.     

Effect of intermittent hypoxia on hematological parameters after recombinant human erythropoietin administration

Recent publications reflect the anti-doping authorities’ concern about the use of altitude simulator systems as violating the spirit of sport criterion (Levine 2006; Loland and Murray 2007; Spriggs 2005). The aim of our study was to determine whether intermittent hypoxic treatments could modify the hemoglobin, hematocrit, reticulocytes, and erythropoietic stimulation index (OFF-Hr Score) values after administration of rHuEPO-alpha. Although these hematological parameters are of secondary nature some international sport federations currently exclude athletes who show aberrant values of these parameters from competition. Ten young male Wistar rats were treated, three times a week for 2 weeks, with 500 IU of rHuEPO-alpha. After the treatment, the animals were randomly divided into two groups: normoxic and hypoxic. The normoxic group was maintained at 21% O₂ 24 h a day for 23 days. The hypoxic group was maintained 12 h at 21% O₂ and 12 h at 12% O₂ (~4,000 m) the same time period. After the rHuEPO-alpha treatment, the hypoxic group of animals had a faster recovery rate in the reticulocyte count, elevated concentrations of hemoglobin and hematocrit and a significant increase in the endogenous EPO levels when compared with the normoxic group of animals. These changes led to significant modifications in the OFF-Hr Score between the hypoxic and normoxic animals. Intermittent hypoxic treatments after rHuEPO administration can significantly modify the main hematological parameters tested by the anti-doping authorities. Our results in an animal model suggest checking the described phenomena in humans in order to reach major conclusions.     

Effect of Arsenic on Regulatory T Cells

Introduction  Arsenic (As) affects the function and survival of lymphocytes, and some arsenic compounds exert a relevant antineoplastic effect. We have explored the effect of As on T regulatory cells. Results and Discussion  In vitro experiments with peripheral blood mononuclear cells from healthy subjects showed that low concentrations of As tended to increase the number of natural T regulatory (nTreg) lymphocytes, whereas concentrations >5.0 μM had an opposite effect. Furthermore, rats exposed to As showed redistribution of nTreg cells, and As administration to rats with experimental allergic encephalomyelitis increased the levels of nTreg cells in spleen and diminished the severity of this condition. On the other hand, in 47 apparently healthy subjects chronically exposed to As, we found significant inverse correlation between urinary As levels and the number and function of nTreg lymphocytes. Although most of these individuals showed enhanced levels of apoptotic lymphocytes in peripheral blood, with a diminution of mitochondrial membrane potential, no significant correlation between these parameters and urinary As was detected. Conclusion  Our data indicate that As seems to have a relevant and complex effect on nTreg cells.     

Effect of in-water recompression with oxygen to 6 msw versus normobaric oxygen breathing on bubble formation in divers

It is generally accepted that the incidence of decompression sickness (DCS) from hyperbaric exposures is low when few or no bubbles are present in the circulation. To date, no data are available on the influence of in-water oxygen breathing on bubble formation following a provocative dive in man. The purpose of this study was to compare the effect of post-dive hyperbaric versus normobaric oxygen breathing (NOB) on venous circulating bubbles. Nineteen divers carried out open-sea field air dives at 30 msw depth for 30 min followed by a 9 min stop at 3 msw. Each diver performed three dives: one control dive, and two dives followed by 30 min of hyperbaric oxygen breathing (HOB) or NOB; both HOB and NOB started 10 min after surfacing. For HOB, divers were recompressed in-water to 6 msw at rest, whereas NOB was performed in a dry room in supine position. Decompression bubbles were examined by a precordial pulsed Doppler. Bubble count was significantly lower for post-dive NOB than for control dives. HOB dramatically suppressed circulating bubble formation with a bubble count significantly lower than for NOB or controls. In-water recompression with oxygen to 6 msw is more effective in removing gas bubbles than NOB. This treatment could be used in situations of “interrupted” or “omitted” decompression, where a diver returns to the water in order to complete decompression prior to the onset of symptoms. Further investigations are needed before to recommend this protocol as an emergency treatment for DCS.     

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration

Background  

Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilize hematopoietic stem cells (HSC) and increase their presence in peripheral circulation.     

An acute oral dose of caffeine does not alter glucose kinetics during prolonged dynamic exercise in trained endurance athletes

This study investigated the possible influence of oral caffeine administration on endogenous glucose production and energy substrate metabolism during prolonged endurance exercise. Twelve trained endurance athletes [seven male, five female; peak oxygen consumption ( ) = 65.5 ml·kg^–1·min^–1] performed 60 min of cycle ergometry at 65% twice, once after oral caffeine administration (6 mg·kg^–1) (CAF) and once following consumption of a placebo (PLA). CAF and PLA were administered in a randomized double-blind manner 75 min prior to exercise. Plasma glucose kinetics were determined with a primed-continuous infusion of [6,6-²H]glucose. No differences in oxygen consumption ( ), and carbon dioxide production ( ) were observed between CAF and PLA, at rest or during exercise. Blood glucose concentrations were similar between the two conditions at rest and also during exercise. Exercise did lead to an increase in serum free fatty acid (FFA) concentrations for both conditions; however, no differences were observed between CAF and PLA. Both the plasma glucose rate of appearance ( ) and disappearance ( ) increased at the onset of exercise (P<0.05), but were not affected by CAF, as compared to PLA. CAF did lead to a higher plasma lactate concentration during exercise (P<0.05). It was concluded that an acute oral dose of caffeine does not influence plasma glucose kinetics or energy substrate oxidation during prolonged exercise in trained endurance athletes. However, CAF did lead to elevated plasma lactate concentrations. The exact mechanism of the increase in plasma lactate concentrations remains to be determined. Electronic Publication     

Oxygen‐sensitive MRI assessment of tumor response to hypoxic gas breathing challenge

Oxygen‐sensitive MRI has been extensively used to investigate tumor oxygenation based on the response (R₂* and/or R₁) to a gas breathing challenge. Most studies have reported response to hyperoxic gas indicating potential biomarkers of hypoxia. Few studies have examined hypoxic gas breathing and we have now evaluated acute dynamic changes in rat breast tumors. Rats bearing syngeneic subcutaneous (n = 15) or orthotopic (n = 7) 13762NF breast tumors were exposed to a 16% O₂ gas breathing challenge and monitored using blood oxygen level dependent (BOLD) R₂* and tissue oxygen level dependent (TOLD) T₁‐weighted measurements at 4.7 T. As a control, we used a traditional hyperoxic gas breathing challenge with 100% O₂ on a subset of the subcutaneous tumor bearing rats (n = 6). Tumor subregions identified as responsive on the basis of R₂* dynamics coincided with the viable tumor area as judged by subsequent H&E staining. As expected, R₂* decreased and T₁‐weighted signal increased in response to 100% O₂ breathing challenge. Meanwhile, 16% O₂ breathing elicited an increase in R₂*, but divergent response (increase or decrease) in T₁‐weighted signal. The T₁‐weighted signal increase may signify a dominating BOLD effect triggered by 16% O₂ in the relatively more hypoxic tumors, whereby the influence of increased paramagnetic deoxyhemoglobin outweighs decreased pO₂. The results emphasize the importance of combined BOLD and TOLD measurements for the correct interpretation of tumor oxygenation properties.     

A low dose of alcohol does not impact skeletal muscle performance after exercise-induced muscle damage

Moderate, acute alcohol consumption after eccentric exercise has been shown to magnify the muscular weakness that is typically associated with exercise-induced muscle damage (EIMD). As it is not known whether this effect is dose-dependent, the aim of this study was to investigate the effect of a low dose of alcohol on EIMD-related losses in muscular performance. Ten healthy males performed 300 maximal eccentric contractions of the quadriceps muscles of one leg on an isokinetic dynamometer. They then consumed either a beverage containing 0.5 g of alcohol per kg bodyweight (as vodka and orange juice) or an isocaloric, isovolumetric non-alcoholic beverage. At least 2 weeks later, they performed an equivalent bout of eccentric exercise on the contralateral leg after which they consumed the other beverage. Measurement of peak and average peak isokinetic (concentric and eccentric) and isometric torque produced by the quadriceps was made before and 36 and 60 h post-exercise. Significant decreases in all measures of muscular performance were observed over time under both conditions (all P < 0.05); however, no difference between treatments was evident at any of the measured time points (all P > 0.05). Therefore, consumption of a low dose of alcohol after damaging exercise appears to have no effect on the loss of force associated with strenuous eccentric exercise.