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PubMed2005

Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster.

The principal objective of the present study was to identify specific alterations in mitochondrial respiratory functions during the aging process. Respiration rates and the activities of electron transport chain complexes were measured at various ages in mitochondria isolated from thoraces of the fruit fly, Drosophila melanogaster, which consist primarily of flight muscles. The rates of state 3 respiration (ADP-stimulated), RCRs (respiratory control ratios) and uncoupled respiration rates decreased significantly as a function of age, using either NAD+- or FAD-linked substrates; however, there were no differences in state 4 respiration (ADP-depleted) rates. There was also a significant age-related decline in the activity of cytochrome c oxidase (complex IV), but not of the other mitochondrial oxidoreductases examined. Exposure of mitochondria isolated from young flies to low doses of KCN or NaAz (sodium azide), complex IV inhibitors, decreased cytochrome c oxidase activity and increased the production of H2O2. Collectively, these results support the hypothesis that impairment of mitochondrial respiration may be a causal factor in the aging process, and that such impairment may result from and contribute to increased H2O2 production in vivo.

Aging↗
PubMed1989

Paradoxical effect of respiration on ventricular rate in atrial fibrillation.

1. In 50 subjects with atrial fibrillation we have attempted to demonstrate variation of ventricular rate with respiration, as evidence of cardioregulatory reflex activity. 2. The electrocardiogram was recorded for 3 min during spontaneous respiration. The presence of respiratory variation of R-R intervals was analysed by multiple regression against a cosine function (cosinor analysis), making it possible to determine the phase of respiration when the intervals were longest. 3. Variation in ventricular rate with respect to respiration was demonstrated (P less than 0.05) in seven (14%) cases. On average, R-R intervals were longest at the end of inspiration; this contrasts with sinus rhythm where P-P, P-R and R-R intervals are longest around the time of end-expiration. 4. These results suggest that in atrial fibrillation the beat-to-beat ventricular rate may be under the influence of cardioregulatory reflexes, but the effect of respiration is weak and paradoxical.

Adult↗
PubMed1999

Oxygen-dependent inhibition of respiration in isolated renal tubules by nitric oxide.

BACKGROUND: The partial pressure (tension) of oxygen (PO2) in the kidney medulla has been established to be lower than that of the cortex. The kidney medulla has been shown to be particularly sensitive to hypoxia. However, the measured PO2 in the kidney medulla is sufficient to support maximal respiration. It has been recently shown that endogenously produced nitric oxide (NO) may inhibit oxygen consumption in the kidney. We studied whether NO plays a role in hypersensitivity of the kidney medulla to hypoxia. METHODS: We studied the effect of added NO on isolated cortical and outer medullary renal tubules in simultaneous oxygen consumption and NO measurements at different oxygen concentrations. RESULTS: We found that NO could potently and reversibly inhibit respiration at nanomolar concentrations. The inhibitory effect of NO was markedly increased at low physiological oxygen concentrations. The effect of NO was cGMP independent because the selective guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) at a 10 microM concentration had no effect on basal or NO-inhibited respiration. The value for half-maximal NO-mediated inhibition of respiration was virtually identical to that found in isolated mitochondria, and therefore, NO was most likely directly acting on mitochondria. Interestingly, we found no differences in sensitivity to NO-mediated inhibition between outer medullary and cortical tubules. CONCLUSIONS: We suggest that because of its low PO2, the renal outer medulla is more sensitive to hypoxia, not because of the low PO2 as such, but probably because of the competition between NO and oxygen to control respiration.

Adenosine Triphosphate↗
PubMed2003

Chronic alcohol consumption increases the sensitivity of rat liver mitochondrial respiration to inhibition by nitric oxide.

Chronic alcohol consumption is a well-known risk factor for hepatic injury, and mitochondrial damage plays a significant role in this process. Nitric oxide (NO) is an important modulator of mitochondrial function and is known to inhibit mitochondrial respiration. However, the impact of chronic alcohol consumption on NO-dependent control of liver mitochondrial function is unknown. This study examines the effect of alcohol exposure on liver mitochondria in a rat model and explores the interaction of NO and mitochondrial respiration in this context. Mitochondria were isolated from the liver of both control and ethanol-fed rats after 5 to 6 weeks of alcohol consumption. Mitochondria isolated from ethanol-treated rats showed a significant decrease in state 3 respiration and respiratory control ratio that was accompanied by an increased sensitivity to NO-dependent inhibition of respiration. In conclusion, we show that chronic alcohol consumption leads to increased sensitivity to the inhibition of respiration by NO. We propose that this results in a greater vulnerability to hypoxia and the development of alcohol-induced hepatotoxicity.

Alcohol Drinking↗
PubMed2005

Partitioning respiration of C3-C4 mixed communities using the natural abundance 13C approach--testing assumptions in a controlled environment.

Contributions of C3 and C4 plants to respiration of C3-C4 ecosystems can be estimated on the basis of their contrasting 13C discrimination. But accurate partitioning requires accurate measurements of the isotope signature of whole system respiratory CO2 (deltaR), and of its members (delta3 and delta4). Unfortunately, experimental determination of representative delta3 and delta4 values is virtually impossible in nature, generating a need for proxies (surrogates) of delta3 and delta4 values (e.g., the delta of leaf biomass). However, recent evidence indicates that there may be systematic differences among the delta of respiratory and biomass components. Thus, partitioning may be biased depending on the proxy. We tested a wide range of biomass- and respiration-based delta proxies for the partitioning of respiration of mixed Lolium perenne (C3) - Paspalum dilatatum (C4) stands growing at two temperatures inside large 13CO2/ 12CO2 gas exchange chambers. Proxy-based partitioning was compared with results of reference methods, including (i) the delta of whole plant respiratory CO2 (delta3 and delta4) or (ii) respiration rate of intact C3 and C4 plants. Results of the reference methods agreed near perfectly. Conversely, some proxies yielded erroneous partitioning results. Partitioning based on either the delta of shoot or root respiratory CO2 produced the worst bias, because shoot respiratory CO2 was enriched in 13C by several per thousand and root respiratory CO2 was depleted by several per thousand relative to whole plant respiratory CO2. Use of whole plant or whole shoot biomass delta gave satisfactory partitioning results under the constant conditions of the experiments, but their use in natural settings is cautioned if environmental conditions are variable and the time scales of respiration partitioning differ strongly from the residence time of C in biomass. Other biomass-based proxies with faster turnover (e.g., leaf growth zones) may be more useful in changing conditions.

Carbon↗
PubMed2006

Extracellular respiration of dimethyl sulfoxide by Shewanella oneidensis strain MR-1.

Shewanella species are renowned for their respiratory versatility, including their ability to respire poorly soluble substrates by using enzymatic machinery that is localized to the outside of the cell. The ability to engage in "extracellular respiration" to date has focused primarily on respiration of minerals. Here, we identify two gene clusters in Shewanella oneidensis strain MR-1 that each contain homologs of genes required for metal reduction and genes that are predicted to encode dimethyl sulfoxide (DMSO) reductase subunits. Molecular and genetic analyses of these clusters indicate that one (SO1427-SO1432) is required for anaerobic respiration of DMSO. We show that DMSO respiration is an extracellular respiratory process through the analysis of mutants defective in type II secretion, which is required for transporting proteins to the outer membrane in Shewanella. Moreover, immunogold labeling of DMSO reductase subunits reveals that they reside on the outer leaflet of the outer membrane under anaerobic conditions. The extracellular localization of the DMSO reductase in S. oneidensis suggests these organisms may perceive DMSO in the environment as an insoluble compound.

Anaerobiosis↗
PubMed2005

Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin.

There is significant evidence that energy production impairment and mitochondrial dysfunction play a role in the pathogenesis of Huntington disease. Nonetheless, the specific mitochondrial defects due to the presence of mutant huntingtin have not been fully elucidated. To determine the effects of mutant huntingtin on mitochondrial energy production, a thorough analysis of respiration, ATP production, and functioning of the respiratory complexes was carried out in clonal striatal cells established from Hdh(Q7) (wild-type) and Hdh(Q111) (mutant huntingtin knock-in) mouse embryos. Mitochondrial respiration and ATP production were significantly reduced in the mutant striatal cells compared with the wild-type cells when either glutamate/malate or succinate was used as the substrate. However, mitochondrial respiration was similar in the two cell lines when the artificial electron donor TMPD/ascorbate, which feeds into complex IV, was used as the substrate. The attenuation of mitochondrial respiration and ATP production when either glutamate/malate or succinate was used as the substrate was not due to impairment of the respiratory complexes, because their activities were equivalent in both cell lines. Intriguingly, in the striatum of presymptomatic and pathological grade 1 Huntington disease cases there is also no impairment of mitochondrial complexes I-IV (Guidetti, P., Charles, V., Chen, E. Y., Reddy, P. H., Kordower, J. H., Whetsell, W. O., Jr., Schwarcz, R., and Tagle, D. A. (2001) Exp. Neurol. 169, 340-350). To our knowledge, this is the first comprehensive analysis of the effects of physiological levels of mutant huntingtin on mitochondrial respiratory function within an appropriate cellular context. These findings demonstrate that the presence of mutant huntingtin impairs mitochondrial ATP production through one or more mechanisms that do not directly affect the function of the respiration complexes.

Adenosine Triphosphate↗
PubMed2006

Respiration correlated cone-beam computed tomography and 4DCT for evaluating target motion in Stereotactic Lung Radiation Therapy.

An image-guidance process for using cone-beam computed tomography (CBCT) for stereotactic body radiation therapy (SBRT) of peripheral lung lesions is presented. Respiration correlated CBCT on the treatment unit and four dimensional computed tomography (4DCT) from planning are evaluated for assessing respiration-induced target motion during planning and treatment fractions. Image-guided SBRT was performed for 12 patients (13 lesions) with inoperable early stage non-small cell lung carcinoma. Kilovoltage (kV) projections were acquired over a 360 degree gantry rotation and sorted based on the pixel value of an image-based aperture located at the air-tissue interface of the diaphragm. The sorted projections were reconstructed to provide volumetric respiration correlated CBCT image datasets at different phases of the respiratory cycle. The 4D volumetric datasets were directly compared with 4DCT datasets acquired at the time of planning. For ten of 12 patients treated, the lung tumour motion, as measured by respiration correlated CBCT on the treatment unit, was consistent with the tumour motion measured by 4DCT at the time of planning. However, in two patients, maximum discrepancies observed were 6 and 10 mm in the anterior-posterior and superior-inferior directions, respectively. Respiration correlated CBCT acquired on the treatment unit allows target motion to be assessed for each treatment fraction, allows target localization based on different phases on the breathing cycle, and provides the facility for adaptive margin design in radiation therapy of lung malignancies. The current study has shown that the relative motion and position of the tumour at the time of treatment may not match that of the planning 4DCT scan. Therefore, application of breathing motion data acquired at simulation for tracking or gating radiation therapy may not be suitable for all patients - even those receiving short course treatment techniques such as SBRT.

Carcinoma, Non-Small-Cell Lung↗
PubMed1981

The physiological responses of mild pulmonary impaired subjects while using a "demand" respirator during rest and work.

This investigation determined the cardiorespiratory responses of subjects with normal lung function and exercise tolerance and compared them with subjects with moderate and severe impairment of lung function and exercise tolerance. Comparisons were made during work while wearing an industrial respirator. The respirator was a full-face mask (MSA-ultravue) "demand" breathing type equipped with an inspiratory resistance of 85 mm H2O at 85 L/min air flow and an expiratory resistance of 25 mm H2O at 85 L/min air flow. Physiologically and subjectively the response of the normal and moderately impaired subjects to respirator wear during rest, 35%, 50% and 63% of their maximal workloads were not different. However, when the moderately impaired worked at 63% of their maximum the workload was equivalent to 50% of maximum of the normal subject. Significant differences in the peak flow/pressure ratio of the severely impaired compared to the normals and moderately impaired were found. By relating work performance to the dyspnea index (VI/MBC) it was suggested that the relationship between maximal lung function and maximal work performance needs to be identified both with and without respirators. This relationship may prove suitable in predicting performance during respirator wear.

Adult↗
PubMed1984

Comparison of mass concentrations determined with personal respirable coal mine dust samplers operating at 1.2 liters per minute and the Casella 113A gravimetric sampler (MRE).

Measuring respirable dust concentrations in coal mine environments is currently done using approved personal respirable dust sampling equipment operating at a flow rate of 2.0 liters per minute (Lpm). Measurements made with approved coal mine dust sampling equipment are converted to equivalent concentrations that would be obtained with a Mining Research Establishment (MRE) instrument known as the Casella 113A gravimetric sampler, using a conversion factor of 1.38. NIOSH has recently recommended that coal mine dust samplers (CMDS) used to measure respirable dust levels in mine environments be operated at 1.2 Lpm and measured concentrations be multiplied by 0.91 to obtain an equivalent MRE concentration. The purpose of this recommendation is to reduce systematic error caused by the variation in mine dust distributions. This paper presents and discusses data collected in the laboratory and in underground coal mines to evaluate the recommended 1.2 Lpm flow rate and 0.91 conversion factor. Comparative measurements were obtained in the laboratory with the CMDS operating at 2.0 and 1.2 liters per minute and the MRE, using aerosols of coal and limestone dust of varying particle size distribution. Similar comparative measurements were made in a number of underground coal mines at locations with environments having particle size distributions representative of different underground mining operations. It was concluded from this study that there is no significant change in the variability associated with the constant factor used to convert respirable dust measurements, obtained with approved respirable CMDS, to equivalent MRE measurements when the flow rate of the CMDS is reduced from 2.0 to 1.2 Lpm.

Coal↗
PubMed2006

Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism.

Cancer cells exhibit increased glycolysis for ATP production due, in part, to respiration injury (the Warburg effect). Because ATP generation through glycolysis is less efficient than through mitochondrial respiration, how cancer cells with this metabolic disadvantage can survive the competition with other cells and eventually develop drug resistance is a long-standing paradox. We report that mitochondrial respiration defects lead to activation of the Akt survival pathway through a novel mechanism mediated by NADH. Respiration-deficient cells (rho(-)) harboring mitochondrial DNA deletion exhibit dependency on glycolysis, increased NADH, and activation of Akt, leading to drug resistance and survival advantage in hypoxia. Similarly, chemical inhibition of mitochondrial respiration and hypoxia also activates Akt. The increase in NADH caused by respiratory deficiency inactivates PTEN through a redox modification mechanism, leading to Akt activation. These findings provide a novel mechanistic insight into the Warburg effect and explain how metabolic alteration in cancer cells may gain a survival advantage and withstand therapeutic agents.

Apoptosis↗
PubMed1997

Influence of heart rate, respiration and recipient atrial contraction on pulsed wave transmitral Doppler flow indices in orthotopic heart transplant recipients.

AIMS: The study set out to assess the relative contributions of donor heart rate, respiration and recipient atrial contraction on the mean of pulsed wave transmitral Doppler flow indices in orthotopic heart transplant recipients. This would provide information on the theoretical usefulness of pacemaker synchronization of recipient atrial contraction, as well as on the validity of certain strategies used for pulsed wave Dopper analysis of diastolic left ventricular function, which have excluded beats based on recipient atrial contraction timing. METHODS: Thirty two consecutive patients undergoing orthotopic heart transplantation in our centre were prospectively studied. The following Doppler indices were analysed: peak early diastolic velocity (E) and its area under the Doppler curve (TVIE), diastolic velocity after donor atrial contraction (A) and its area under the curve (TVIA), the total area under the curve (TVI), the isovolumic relaxation period (IVR), the diastolic filling period, the normalized peak filling rate and the pressure half time. RESULTS: Only 81 out of 347 recordings (23%) allowed analysis of the recipient P wave and thus recipient atrial contraction timing, heart rate and the respiration phase in 22 patients for a total of 1579 beats. The isovolumic relaxation period, E, pressure half time and TVIA are not influenced by donor heart rate. For the isovolumic relaxation period, E, TVI and TVIE, respiration contributes as much as recipient atrial contraction timing to beat-to-beat variation. Pressure half time, the diastolic filling period and peak filling rate were not affected by respiration. TVI was not affected by recipient atrial contraction timing. CONCLUSION: With respect to analysis of diastolic function, exclusion of beats based on recipient atrial contraction timing is invalid for the isovolumic relaxation period. E, TVI and TVIE, since these are equally influenced by respiration. Since TVI was not affected by recipient atrial contraction timing, pacemaker synchronization of donor and recipient atria is not expected to be useful in patients with left ventricular diastolic dysfunction.

Atrial Function↗
PubMed1999

Uptake of 10 polar organic solvents during short-term respiration.

Respiratory uptake was investigated for 10 polar organic solvents with high blood/air partition coefficients (lambda(blood/air)): ethyl acetate (lambda(blood/air), 77), methyl iso-butyl ketone (90), methyl acetate (90), methyl propyl ketone (150), acetone (245), iso-pentyl alcohol (381), iso-propyl alcohol (848), methyl alcohol (2590), ethylene glycol monobutyl ether (EGBE, 7970), and propylene glycol monomethyl ether (PGME, 12380). Test-air concentrations (Cinh) were 25 to 200 ppm. Four healthy male volunteers inhaled the test air for 10 min at rest and then room air for 5 min. The percentage of solvent in the end-exhaled air and in the mixed-exhaled air increased after the start of the test-air respiration, and reached a quasi-steady-state level within a few min. The speeds of these increases at the start of the test-air respiration became lower as lambda(blood/air) increased. The mean uptakes (U) for the last five min of the test air respiration were 67.3, 52.9, 60.4, 53.0, 52.6, 63.0, 60.3, 60.8, 79.7, and 81.3%, respectively, for ethyl acetate, methyl iso-butyl ketone, methyl acetate, methyl propyl ketone, acetone, iso-pentyl alcohol, iso-propyl alcohol, methyl alcohol, EGBE and PGME. Thus, U values of the alcohols were higher than those of the ketones and lower than the glycol ethers. The overall view, except for esters, showed that U increased with lambda(water/air) increases. This tendency can be explained by a hypothesis that solvent absorbed in the mucus layer of the respiratory tract is removed by the bronchial blood circulation. U values of ethyl acetate and methyl acetate were higher than those of methyl iso-butyl ketone and methyl propyl ketone, though the lambda(blood/air) values of these esters were nearly equal to those of the ketones. For the respiration of the esters, their metabolites, ethyl alcohol and methyl alcohol, were detected in the exhaled air. The exhalation percentage of the metabolites increased after the start of test-air respiration and reached a quasi-steady-state level of 2 and 3%, respectively, by the 5th min. These data suggest that removal of the solvent via metabolism in the wall tissue of the respiratory tract plays an important role for the esters.

Administration, Inhalation↗
PubMed2002

Leaf respiration at different canopy positions in sweetgum (Liquidambar styraciflua) grown in ambient and elevated concentrations of carbon dioxide in the field.

Trees exposed to elevated CO2 partial pressure ([CO2]) generally show increased rates of photosynthesis and growth, but effects on leaf respiration are more variable. The causes of this variable response are unresolved. We grew 12-year-old sweetgum trees (Liquidambar styraciflua L.) in a Free-Air CO2 Enrichment (FACE) facility in ambient [CO2] (37/44 Pa daytime/nighttime) and elevated [CO2] (57/65 Pa daytime/nighttime) in native soil at Oak Ridge National Environmental Research Park. Nighttime respiration (R(N)) was measured on leaves in the upper and lower canopy in the second (1999) and third (2000) growing seasons of CO2 fumigation. Leaf respiration in the light (R(L)) was estimated by the technique of Brooks and Farquhar (1985) in the upper canopy during the third growing season. There were no significant short-term effects of elevated [CO2] on R(N) or long-term effects on R(N) or R(L), when expressed on an area, mass or nitrogen (N) basis. Upper-canopy leaves had 54% higher R(N) (area basis) than lower-canopy leaves, but this relationship was unaffected by CO2 growth treatment. In August 2000, R(L) was about 40% of R(N) in the upper canopy. Elevated [CO(2)] significantly increased the number of leaf mitochondria (62%), leaf mass per unit area (LMA; 9%), and leaf starch (31%) compared with leaves in ambient [CO(2)]. Upper-canopy leaves had a significantly higher number of mitochondria (73%), N (53%), LMA (38%), sugar (117%) and starch (23%) than lower-canopy leaves. Growth in elevated [CO2] did not affect the relationships (i.e., intercept and slope) between R(N) and the measured leaf characteristics. Although no factor explained more than 45% of the variation in R(N), leaf N and LMA were the best predictors for R(N). Therefore, the response of RN to CO2 treatment and canopy position was largely dependent on the magnitude of the effect of elevated [CO2] or canopy position on these characteristics. Because elevated [CO2] had little or no effect on N or LMA, there was no effect on R(N). Canopy position had large effects on these leaf characteristics, however, such that upper-canopy leaves exhibited higher R(N) than lower-canopy leaves. We conclude that elevated [CO2] does not directly impact leaf respiration in sweetgum and that barring changes in leaf nitrogen or leaf chemical composition, long-term effects of elevated [CO2] on respiration in this species will be minimal.

Carbohydrates↗
PubMed2004

Seasonal and annual changes in soil respiration in relation to soil temperature, water potential and trenching.

Soil respiration (rs), soil temperature (Ts) and volumetric soil water content were measured in a balsam fir (Abies balsamea (L.) Mill.) ecosystem from 1998 to 2001. Seasonal variation in root and microbial respiration, and covariation in abiotic factors confounded interpretation of the effects of Ts and soil water potential (Psis) on rs. To minimize the confounding effect of temperature, we analyzed the effect of Psis on rs during the summers of 1998-2000 when changes in Ts were slight. Soil respiration declined 25-50% in response to modest water stress (minimum Psis of -0.6 to -0.2 MPa), and between years, there was substantial variation in the relationship between rs and Psis. In the summer of 2000, 2-m2 plots were subjected to drought for 1 month and other plots were irrigated. The relationship between summertime rs and Psis in the experimental plots was similar to that estimated from the survey data obtained during the same summer. In late spring and early autumn of 2001, 2-m2 trenched and untrenched plots were subjected to drought or exposed to rainfall. It was dry in the early autumn and there was severe soil drying (Psis of -10 MPa in untrenched plots and -2 MPa in trenched plots). In spring, rs in untrenched plots responded more to modest water stress than rs in trenched plots, indicating that root respiration is more sensitive than microbial respiration to water stress at this time of year. The response to abiotic factors differed significantly between spring and autumn in untrenched plots but not in trenched plots, indicating that root activity was greater in early autumn than in late spring, and that roots acclimated to the sustained, severe water stress experienced before and during the autumn.

Abies↗
PubMed2004

Measurement and interpretation of the oxygen isotope composition of carbon dioxide respired by leaves in the dark.

We measured the oxygen isotope composition (delta(18)O) of CO(2) respired by Ricinus communis leaves in the dark. Experiments were conducted at low CO(2) partial pressure and at normal atmospheric CO(2) partial pressure. Across both experiments, the delta(18)O of dark-respired CO(2) (delta(R)) ranged from 44 per thousand to 324 per thousand (Vienna Standard Mean Ocean Water scale). This seemingly implausible range of values reflects the large flux of CO(2) that diffuses into leaves, equilibrates with leaf water via the catalytic activity of carbonic anhydrase, then diffuses out of the leaf, leaving the net CO(2) efflux rate unaltered. The impact of this process on delta(R) is modulated by the delta(18)O difference between CO(2) inside the leaf and in the air, and by variation in the CO(2) partial pressure inside the leaf relative to that in the air. We developed theoretical equations to calculate delta(18)O of CO(2) in leaf chloroplasts (delta(c)), the assumed location of carbonic anhydrase activity, during dark respiration. Their application led to sensible estimates of delta(c), suggesting that the theory adequately accounted for the labeling of CO(2) by leaf water in excess of that expected from the net CO(2) efflux. The delta(c) values were strongly correlated with delta(18)O of water at the evaporative sites within leaves. We estimated that approximately 80% of CO(2) in chloroplasts had completely exchanged oxygen atoms with chloroplast water during dark respiration, whereas approximately 100% had exchanged during photosynthesis. Incorporation of the delta(18)O of leaf dark respiration into ecosystem and global scale models of C(18)OO dynamics could affect model outputs and their interpretation.

Carbon Dioxide↗
PubMed1984

Respiration as a reliable physiological sensor for controlling cardiac pacing rate.

A study was carried out to determine whether variations in the respiration rate during physical exercise could be used as a physiological variable in controlling the rate of an implanted pacemaker. The relation between respiration rate and heart rate was significantly correlated in 73 patients (19 with normal lung function, four with restrictive pulmonary disease, and 50 with obstructive airways disease) during repeated calibrated ergometric tests; no significant differences were found between the subgroups. An external computerised programmable system with algorithm control activated by a radio frequency system was used to vary the cardiac stimulation rate in relation to respiration rate in 11 patients implanted with ventricular inhibited pacemakers. In addition, a prototype programmable pacemaker dependent on respiration rate was implanted in two patients. Maximum values of oxygen uptake, minute ventilation, and work time were increased during the exercise stress tests when the variable cardiac pacing rate was used. Thus respiration rate appears to be a valid and stable physiological variable for controlling the cardiac stimulation rate in order to improve cardiac output in patients dependent on pacemakers.

Aged↗
PubMed2003

Oxygen regulation and limitation to cellular respiration in mouse skeletal muscle in vivo.

In skeletal muscle, intracellular Po2 can fall to as low as 2-3 mmHg. This study tested whether oxygen regulates cellular respiration in this range of oxygen tensions through direct coupling between phosphorylation potential and intracellular Po2. Oxygen may also behave as a simple substrate in cellular respiration that is near saturating levels over most of the physiological range. A novel optical spectroscopic method was used to measure tissue oxygen consumption (Mo2) and intracellular Po2 using the decline in hemoglobin and myoglobin saturation in the ischemic hindlimb muscle of Swiss-Webster mice. 31P magnetic resonance spectroscopic determinations yielded phosphocreatine concentration ([PCr]) and pH in the same muscle volume. Intracellular Po2 fell to <2 mmHg during the ischemic period without a change in the muscle [PCr] or pH. The constant phosphorylation state despite the decline in intracellular Po2 rejects the hypothesis that direct coupling between these two variables results in a regulatory role for oxygen in cellular respiration. A second set of experiments tested the relationship between intracellular Po2 and Mo2. In vivo Mo2 in mouse skeletal muscle was increased by systemic treatment with 2 and 4 mg/kg body wt 2,4-dinitrophenol to partially uncouple mitochondria. Mo2 was not dependent on intracellular Po2 above 3 mmHg in the three groups despite a threefold increase in Mo2. These results indicate that Mo2 and the phosphorylation state of the cell are independent of intracellular Po2 throughout the physiological range of oxygen tensions. Therefore, we reject a regulatory role for oxygen in cellular respiration and conclude that oxygen acts as a simple substrate for respiration under physiological conditions.

2,4-Dinitrophenol↗