Oxygen uptake during early cardiogenesis of the chick.

Oxidative metabolism of the isolated embryonic heart of the chick has been determined using a spectrophotometric technique allowing global as well as localized micromeasurements of the O2 uptake. Entire hearts, excised from embryos of 10 somites (primordia fused, stage 10 HH) and 40 somites (S shaped, stage 20 HH) were placed in a special chamber under controlled metabolic conditions where they continued to beat spontaneously and regularly. During the 32 h of development, the O2 consumption of the whole heart increased from 0.9 +/- 0.1 to 5.3 +/- 0.8 nmol O2/h. These values corrected for protein content were, however, comparable (0.45 nmol O2.h-1.micrograms-1). At stage 10-12, the O2 uptake varied along the cardiac tube (from 0.74 to 1.0 nmol O2.h-1.mm-2). From stage 10 to 20, the O2 uptake per unit area of ventricle wall increased from 0.7 +/- 0.2 to 1.8 +/- 0.2 nmol O2.h-1.mm-2, and the O2 uptake per myocardial volume during one cardiac cycle varied from 7 to 2.5 nmol O2/cm3. These results indicate that, despite an intense morphogenesis, the cardiac tissue has a rather low and stable oxidative metabolism, although the O2 requirement of the whole heart increases significantly. Moreover, the normalized suprabasal aerobic energy expenditure decreases throughout early cardiogenesis. The functional integrity of the isolated embryonic heart combined with the experimental possibilities of the microtechnique make the preparation appropriate for studying the changes in cardiac metabolism during development.

Long-term transcutaneous monitoring of oxygen tension and carbon dioxide at 42 degrees C in critically ill neonates: improved performance of the tcpo2 monitor with topical metabolic inhibition.

Whereas during the last few years handling of the transcutaneous PO2 (tcPO2) and PCO2 (tcPCO2) sensor has been simplified, the high electrode temperature and the short application time remain major drawbacks. In order to determine whether the application of a topical metabolic inhibitor allows reliable measurement at a sensor temperature of 42 degrees C for a period of up to 12 h, we performed a prospective, open, nonrandomized study in a sequential sample of 20 critically ill neonates. A total of 120 comparisons (six repeated measurements per patient) between arterial and transcutaneous values were obtained. Transcutaneous values were measured with a control sensor at 44 degrees C (conventional contact medium, average application time 3 h) and a test sensor at 42 degrees C (Eugenol solution, average application time 8 h). Comparison of tcPO2 and PaO2 at 42 degrees C (Eugenol solution) showed a mean difference of +0.16 kPa (range +1.60 to -2.00 kPa), limits of agreement +1.88 and -1.56 kPa. Comparison of tcPO2 and PaO2 at 44 degrees C (control sensor) revealed a mean difference of +0.02 kPa (range +2.60 to -1.90 kPa), limits of agreement +2.12 and -2.08 kPa. Comparison of tcPCO2 and PaCO2 at 42 degrees C (Eugenol solution) showed a mean difference of +0.91 (range +2.30 to +0.10 kPa), limits of agreement +2.24 and -0.42 kPa. Comparison of tcPCO2 and PaCO2 at 44 degrees C (control sensor) revealed a mean difference of +0.63 kPa (range 1.50 to -0.30 kPa), limits of agreement +1.73 and -0.47 kPa. CONCLUSION: Our results show that the use of an Eugenol solution allows reliable measurement of tcPO2 at a heating temperature of 42 degrees C; the application time can be prolongued up to a maximum of 12 h without aggravating the skin lesions. The performance of the tcPCO2 monitor was slightly worse at 42 degrees C than at 44 degrees C suggesting that for the Eugenol solution the metabolic offset should be corrected.

Impact of reduced cerebral perfusion pressure on outcome after severe traumatic brain injury is dependent on brain tissue oxygen pressure

INTRODUCTION. Reduced cerebral perfusion pressure (CPP) may worsen secondary damage and outcome after severe traumatic brain injury (TBI), however the optimal management of CPP is still debated. STUDY HYPOTHESIS: We hypothesized that the impact of CPP on outcome is related to brain tissue oxygen tension (PbtO2) level and that reduced CPP may worsen TBI prognosis when it is associated with brain hypoxia. DESIGN. Retrospective analysis of prospective database. METHODS. We analyzed 103 patients with severe TBI who underwent continuous PbtO2 and CPP monitoring for an average of 5 days. For each patient, duration of reduced CPP (\60 mm Hg) and brain hypoxia (PbtO2\15 mm Hg for[30 min [1]) was calculated with linear interpolation method and the relationship between CPP and PbtO2 was analyzed with Pearson's linear correlation coefficient. Outcome at 30 days was assessed with the Glasgow Outcome Score (GOS), dichotomized as good (GOS 4-5) versus poor (GOS 1-3). Multivariable associations with outcome were analyzed with stepwise forward logistic regression. RESULTS. Reduced CPP (n=790 episodes; mean duration 10.2 ± 12.3 h) was observed in 75 (74%) patients and was frequently associated with brain hypoxia (46/75; 61%). Episodes where reduced CPP were associated with normal brain oxygen did not differ significantly between patients with poor versus those with good outcome (8.2 ± 8.3 vs. 6.5 ± 9.7 h; P=0.35). In contrast, time where reduced CPP occurred simultaneously with brain hypoxia was longer in patients with poor than in those with good outcome (3.3±7.4 vs. 0.8±2.3 h; P=0.02). Outcome was significantly worse in patients who had both reduced CPP and brain hypoxia (61% had GOS 1-3 vs. 17% in those with reduced CPP but no brain hypoxia; P\0.01). Patients in whom a positive CPP-PbtO2 correlation (r[0.3) was found also were more likely to have poor outcome (69 vs. 31% in patients with no CPP-PbtO2 correlation; P\0.01). Brain hypoxia was an independent risk factor of poor prognosis (odds ratio for favorable outcome of 0.89 [95% CI 0.79-1.00] per hour spent with a PbtO2\15 mm Hg; P=0.05, adjusted for CPP, age, GCS, Marshall CT and APACHE II). CONCLUSIONS. Low CPP may significantly worsen outcome after severe TBI when it is associated with brain tissue hypoxia. PbtO2-targeted management of CPP may optimize TBI therapy and improve outcome of head-injured patients.

Nonenzymatic oxidation of trienoic fatty acids contributes to reactive oxygen species management in Arabidopsis.

In higher plants such as Arabidopsis thaliana, omega-3 trienoic fatty acids (TFAs), represented mainly by alpha-linolenic acid, serve as precursors of jasmonic acid (JA), a potent lipid signal molecule essential for defense. The JA-independent roles of TFAs were investigated by comparing the TFA- and JA-deficient fatty acid desaturase triple mutant (fad3-2 fad7-2 fad8 (fad3 fad7 fad8)) with the aos (allene oxide synthase) mutant that contains TFAs but is JA-deficient. When challenged with the fungus Botrytis, resistance of the fad3 fad7 fad8 mutant was reduced when compared with the aos mutant, suggesting that TFAs play a role in cell survival independently of being the precursors of JA. An independent genetic approach using the lesion mimic mutant accelerated cell death2 (acd2-2) confirmed the importance of TFAs in containing lesion spread, which was increased in the lines in which the fad3 fad7 fad8 and acd2-2 mutations were combined when compared with the aos acd2-2 lines. Malondialdehyde, found to result from oxidative TFA fragmentation during lesion formation, was measured by gas chromatography-mass spectrometry. Its levels correlated with the survival of the tissue. Furthermore, plants lacking TFAs overproduced salicylic acid (SA), hydrogen peroxide, and transcripts encoding several SA-regulated and SA biosynthetic proteins. The data suggest a physiological role for TFAs as sinks for reactive oxygen species.

Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: Therapeutic potential of mitochondrially targeted antioxidants.

Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-α, MIP-1α/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6h of reperfusion and peaking at 24h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage.

Interstitial cells of Cajal are normally distributed in both ganglionated and aganglionic bowel in Hirschsprung's disease

Résumé Introduction : La chirurgie de la maladie de Hirschsprung est fréquemment compliquée d'une atteinte post-opératoire de la motilité intestinale. Des anomalies du système nerveux entérique (SNE) telles que la dysplasie neuronale intestinale de type B, l'hypoganglionose ou l'aganglionose, présents dans le segment abaissé, peuvent être la cause de certaines de ces complications mais aucune information n'est disponible quant au rôle des cellules interstitielles de Cajal (CIC) sur la motilité intestinale dans la phase post-opératoire. Ces cellules sont considérées avoir un rôle de pacemaker dans le tractus gastro-intestinal. L'objectif de cette étude était de décrire la distribution des CIC dans le segment proximal du côlon réséqué lors de cures chirurgicales de maladie de Hirschsprung et de confronter ces observations à l'évolution clinique post-opératoire. Matériel et Méthodes : L'incidence des complications post-opératoires a été déterminée par une revue rétrospective des dossiers de 48 patients opérés pour maladie de Hirschspung entre 1977 et 1999 et par l'étude histologique et immuno-histochimique des pièces réséquées chez ces patients. Nous avons comparé la distribution des CIC dans le segment proximal du côlon avec celle du côlon sain de 16 enfants contrôles par microscopie optique. L'immunohistochimie au c-Kit a été utilisée pour marquer spécifiquement les CIC sur échantillons paraffinés. Ces résultats ont ensuite été corrélés avec l'étude du SNE de ces mêmes segments, déterminée par immunohistochimie au CD56 et au protein gene product 9.5. Résultats Les complications post-opératoires suivantes furent identifiées : constipation 46%, constipation avec incontinence 15%, entérocolite 8%, décès 4% (probablement sur entérocolite). La distribution des CIC dans les segments proximaux réséqués chez les enfants avec maladie de Hirschsprung était identique à celle observée dans les segments de côlon sain, et ce indépendamment de la distribution normale ou anormale du SNE. Chez les enfants opérés pour maladie de Hirschsprung les segments réséqués présentaient les anomalies d'innervation suivantes : aganglionose 10.4%, hypoganglionose 12.5%, dysplasie neuronale intestinale de type B 6.3%, autres dysganglionoses 14.6%. Aucune relation entre ces anomalies d'innervation et les complications post-opératoires n'a été mise en évidence. Conclusion : La distribution des CIC est normale chez les patient opérés pour maladie de Hirschsprung, et ne contribue donc pas aux atteintes post-opératoires de la motilité intestinale. Cela signifie aussi que le réseau de CIC se développe noinialement dans le côlon humain, même en présence d'une innervation colique anormale ou absente. Abstract: Surgery for Hirschsprung's disease is often complicated by post-operative bowel motility disorders. The impact of intestinal neural histology on the surgical outcome has been previously studied, but no information is available concerning the influence of the distribution of interstitial cells of Cajal (ICC) on these complications. These cells are considered to be pacemakers in the gastrointestinal tract. The aim of this study was to assess the distribution of ICC in the proximal segment of resected bowel in Hirschsprung's disease and confront these results with the clinical outcome. Using immunohistochemistry for light microscopy, we compared the pattern of distribution of ICC in the proximal segment of resected bowel in Hirschsprung's disease with that in normal colon. We correlated these results with the corresponding neural intestinal histology determined by CD56 and the protein gene product 9.5 immunohistochemistry. The distribution of ICC in the proximal segment of resected bowel is identical to that of normal colon, regardless of normal or abnormal colon innervation. ICC distribution does not seem to contribute to post-operative bowel motility disorders in patients operated for Hirschsprung's disease.

Hyperthermia and maximal oxygen uptake in men and women.

To compare the effect of hyperthermia on maximal oxygen uptake (VO2max) in men and women, VO2max was measured in 11 male and 11 female runners under seven conditions involving various ambient temperatures (Ta at 50% RH) and preheating designed to manipulate the esophageal (Tes) and mean skin (Tsk) temperatures at VO2max. The conditions were: 25 degrees C, no preheating (control); 25, 35, 40, and 45 degrees C, with exercise-induced preheating by a 20-min walk at approximately 33% of control VO2max; 45 degrees C, no preheating; and 45 degrees C, with passive preheating during which Tes and Tsk were increased to the same degree as at the end of the 20-min walk at 45 degrees C. Compared to VO2max (l x min(-1)) in the control condition (4.52+/-0.46 in men, 3.01+/-0.45 in women), VO2max in men and women was reduced with exercise-induced or passive preheating and increased Ta, approximately 4% at 35 degrees C, approximately 9% at 40 degrees C and approximately 18% at 45 degrees C. Percentage reductions (7-36%) in physical performance (treadmill test time to exhaustion) were strongly related to reductions in VO2max (r=0.82-0.84). The effects of hyperthermia on VO2max and physical performance in men and women were almost identical. We conclude that men and women do not differ in their thermal responses to maximal exercise, or in the relationship of hyperthermia to reductions in VO2max and physical performance at high temperature. Data are reported as mean (SD) unless otherwise stated.

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT), or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.

Reliability of stable carbon and oxygen isotope compositions of pedogenic needle fibre calcite as environmental indicators: examples from Western Europe.

Stable carbon and oxygen isotope analyses were conducted on pedogenic needle fibre calcite (NFC) from seven sites in areas with roughly similar temperate climates in Western Europe, including the Swiss Jura Mountains, eastern and southern France, northern Wales, and north-eastern Spain. The δ(13)C values (-12.5 to-6.8 0/00 Vienna Pee Dee Belemnite (VPDB)) record the predominant C(3) vegetation cover at the sites. A good correlation was found between mean monthly climatic parameters (air temperature, number of frost days, humidity, and precipitation) and δ(18)O values (-7.8 to-3.40/00 VPDB) of all the NFC. Similar seasonal variations of δ(18)O values for monthly NFC samples from the Swiss sites and those of mean monthly δ(18)O values of local precipitation and meteorological data point out precipitation and preferential growth/or recrystallisation of the pedogenic needle calcite during dry seasons. These covariations indicate the potential of stable isotope compositions of preserved NFC in fossil soil horizons as a promising tool for palaeoenvironmental reconstructions.

Right-left digit ratio (2D:4D) and maximal oxygen uptake.

A low digit ratio (2D:4D) and low 2D:4D in the right compared with the left hand (right-left 2D:4D) are thought to be determined by high in utero concentrations of testosterone, and are related to "masculine" traits such as aggression and performance in sports like running and rugby. Low right-left 2D:4D is also related to sensitivity to testosterone as measured by the number of cytosine-adenine-guanine triplet repeats in exon 1 of the androgen receptor gene. Here we show that low right-left 2D:4D is associated with high maximal oxygen uptake (VO2(max)), high velocity at VO2(max), and high maximum lactate concentration in a sample of teenage boys. We suggest that low right-left 2D:4D is linked to performance in some sports because it is a proxy of high sensitivity to prenatal and maybe also circulating testosterone and high VO2(max).

Controls on ostracod valve geochemistry, Part 1: Variations of environmental parameters in ostracod (micro-)habitats

The variations of environmental conditions (T°, pH, δ13CDIC, [DIC], δ18O, Mg/Ca, and Sr/Ca) of ostracod habitats were examined to determine the controls of environmental parameters on the chemical and isotopic composition of ostracod valves. Results of a one-year monitoring of environmental parameters at five sites, with depths of between 2 and 70 m, in Lake Geneva indicate that in littoral to sub-littoral zones (2, 5, and 13 m), the chemical composition of bottom water varies seasonally in concert with changes in temperature and photosynthetic activity. An increase of temperature and photosynthetic activity leads to an increase in δ13C values of DIC and to precipitation of authigenic calcite, which results in a concomitant increase of Mg/Ca and Sr/Ca ratios of water. In deeper sites (33 and 70 m), the composition of bottom water remains constant throughout the year and isotopic values and trace element contents are similar to those of deep water within the lake. The chemical composition of interstitial pore water also does not reflect seasonal variations but is controlled by calcite dissolution, aerobic respiration, anaerobic respiration with reduction of sulphate and/or nitrate, and methanogenesis that may occur in the sediment pores. Relative influence of each of these factors on the pore water geochemistry depends on sediment thickness and texture, oxygen content in bottom as well as pore water. Variations of chemical compositions of the ostracod valves of this study vary according to the specific ecology of the ostracod species analysed, that is its life-cycle and its (micro-)habitat. Littoral species have compositions that are related to the seasonal variations of temperature, δ13C values of DIC, and of Mg/Ca and Sr/Ca ratios of water. In contrast, the compositions of profundal species are largely controlled by variations of pore fluids along sediment depth profiles according to the specific depth preference of the species. The control on the geochemistry of sub-littoral species is a combination of controls for the littoral and profundal species as well as the specific ecology of the species.

Effects of dopamine on total oxygen consumption and oxygen delivery in healthy men.

The effect of acute intravenous dopamine (DA) administration at three sequential (but randomized) infusion rates was studied in eight young male volunteers. DA was infused at 2.5, 5, and 10 micrograms.kg-1.min-1. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by means of a computerized indirect calorimeter (blood system). In response to the 5- and 10-micrograms.kg-1.min-1 DA infusion rates, a significant increase (P less than 0.01) in VO2 corresponding to a 6% (range, 3-10) and 15% (range, 12-23) increase, respectively, of preinfusion values was observed. In contrast, at the low dose (2.5 micrograms.kg-1.min-1), DA induced no significant change in VO2. Cardiac output (Qc) increased significantly after the three DA administration rates [19% (range, 0-42), 34% (range, 17-71), and 25% (range, -3 to +47)] for the doses 2.5, 5, and 10 micrograms.-kg-1.min-1, respectively. The increase in O2 delivery (QO2) outweighed VO2 at all administration rates despite the relative drop in QO2 at the maximal DA administration rate. These results indicate that in humans DA improves net O2 supply to tissues proportionally more than it increases VO2 at all doses used in the present study.

Bronchiolite respiratoire et bronchiolite respiratoire avec pneumopathie interstitielle [Respiratory bronchiolitis and respiratory bronchiolitis-associated interstitial lung disease].

The increasing use of chest CT imaging in medical practice rises the likelihood of the general practitioner to be confronted with cases of interstitial lung disease. Respiratory bronchiolitis (RB) and respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are two smoking-related lung damages that may have important implications for the patient's management. The authors present in this paper a review of current knowledge of the epidemiology, clinical features, prognosis, and treatment options of RB and RB-ILD.