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PubMed2005

Light-enhanced dark respiration in leaves, isolated cells and protoplasts of various types of C4 plants.

The rate of respiratory CO2 evolution from the leaves of Zea mays, Panicum miliaceum, and Panicum maximum, representing NADP-ME, NAD-ME, and PEP-CK types of C4 plants, respectively, was increased by approximately two to four times after a period of photosynthesis. This light-enhanced dark respiration (LEDR) was a function of net photosynthetic rate specific to plant species, and was depressed by 1% O2. When malate, aspartate, oxaloacetate or glycine solution at 50 mM concentration was introduced into the leaves instead of water, the rate of LEDR was enhanced, far less in Z. mays (by 10-25%) than in P. miliaceum (by 25-35%) or P. maximum (by 40-75%). The enhancement of LEDR under glycine was relatively stable over a period of 1 h, whereas the remaining metabolites caused its decrease following a transient increase. The metabolites reduced the net photosynthesis rate in the two Panicum species, but not in Z. mays, where this process was stimulated by glycine. The bundle sheath cells from P. miliaceum exhibited a higher rate of LEDR than those of Z. mays and P. maximum. Glycine had no effect on the respiration rate of the cells, but malate increased in cells of Z. mays and P. miliaceum by about 50% and 30%, respectively. With the exception of aspartate, which stimulated both the O2 evolution and O2 uptake in P. maximum, the remaining metabolites reduced photosynthetic O2 evolution from bundle sheath cells in Panicun species. The net O2 exchange in illuminated cells of Z. mays did not respond to CO2 or metabolites. Leaf mesophyll protoplasts of Z. mays and P. miliaceum, and bundle sheath protoplasts of Z. mays, which are unable to fix CO2 photosynthetically, also produced LEDR, but the mesophyll protoplasts, compared with bundle sheath protoplasts, required twice the time of illumination to obtain the maximal rate. The results suggest that the substrates for LEDR in C4 plants are generated during a period of illumination not only via the Calvin cycle reactions, but also by the conversion of endogenous compounds present in leaf cells. The stimulation of LEDR under glycine is discussed in relation to its direct or indirect effect on mitochondrial respiration.

Aspartic Acid↗

PubMed2006

Wy-14,643 and fenofibrate inhibit mitochondrial respiration in isolated rat cardiac mitochondria.

We investigated the direct effects of two selective PPARalpha ligands, fenofibrate and Wy-14,643, on mitochondrial respiratory function using isolated rat cardiac mitochondria. Isolated left ventricular mitochondria were incubated with increasing concentrations of fenofibrate or Wy-14,643 (10, 100, and 500 microM) and mitochondrial respiration determined using: malate/glutamate (complex I), succinate (complex II) and palmitoyl-l-carnitine as oxidative substrates. Our data show that acute exposure to Wy-14,643 and fenofibrate differentially perturb cardiac mitochondrial respiration i.e., fenofibrate more potently inhibited mitochondrial respiration and bioenergetic capacity compared to Wy-14,643. Moreover, we found that both agents increased uncoupling of mitochondrial oxidative phosphorylation.

Animals↗

PubMed2005

Synergistic inhibition of respiration in brain mitochondria by nitric oxide and dihydroxyphenylacetic acid (DOPAC). Implications for Parkinson's disease.

The inhibition of mitochondrial respiration by nitric oxide (.NO) at cytochrome c oxidase level has been established as a physiological regulatory mechanism of mitochondrial function. Given, on the one hand, the potential involvement of .NO and dopamine metabolism in mitochondrial dysfunction associated with neurodegeneration and, on the other hand, the reported interaction of .NO with dihydroxyphenylacetic acid (DOPAC), a major mitochondrial-associated dopamine metabolite, we examined the combined effects of .NO and DOPAC on the respiratory chain of isolated rat brain mitochondria. Whereas dopamine or DOPAC induced no measurable effects on the mitochondrial respiration rate, a mixture of .NO with DOPAC inhibited the rate in a way stronger than that exerted by .NO. This effect was noticed with actively respiring (state 3) and resting (state 4) mitochondria. At variance with DOPAC, dopamine failed to potentiate .NO inhibitory effects. The inhibition was dependent on the concentration of both compounds, .NO and DOPAC, and exhibited characteristics similar to those exerted by .NO, namely: it was reversible and dependent on the concentration of oxygen. Analysis of respiratory enzymatic activities demonstrated a selective inhibition at the level of cytochrome c oxidase (complex IV). Insights into the chemical mechanisms underlying the inhibitory effect were inferred from experiments using metmyoglobin (a ligand for .NO and derived species, such as nitroxyl anion) and ferrocyanide (a reductant of .NO, producing nitroxyl anion). Whereas metmyoglobin decreased the inhibition, ferrocyanide potentiated the inhibition. Moreover, a mixture of ferrocyanide with .NO reproduced the effects exerted by the mixture of .NO with DOPAC. The results are consistent with the notion of a reaction of .NO with DOPAC producing a nitric oxide-derived compound(s), which inhibit O2 uptake at the cytochrome oxidase level. Although the mechanism in question remains to be clearly elucidated it is suggested that the .NO/DOPAC-dependent inhibition of cytochrome oxidase may involve nitroxyl anion. The significance of these observations for mitochondrial dysfunction inherent in Parkinson's disease is discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2003

Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids.

The alkaloids from Chelidonium majus L. which had a significant inhibitory effect in mitochondrial respiration were those which contain a positive charge due to a quaternary nitrogen atom, i.e., chelerythrine, sanguinarine, berberine and coptisine, both with malate+glutamate or with succinate as substrates. When malate+glutamate was used as substrate, chelerythrine and berberine, which contain methoxy groups, were particularly more active, since they had a strong effect even at low concentrations. In submitochondrial particles, berberine and coptisine had a marked inhibitory effect on NADH dehydrogenase activity but practically no effect on succinate dehydrogenase activity, whereas chelerythrine and sanguinarine inhibited more strongly succinate dehydrogenase than NADH dehydrogenase, which is in agreement with the results found for mitochondrial respiration. Protopine and allocryptopine, which did not inhibit mitochondrial respiration, strongly inhibited NADH dehydrogenase in submitochondrial particles, but had no effect on succinate dehydrogenase activity.

Alkaloids↗

PubMed1997

An investigation of respiration while wearing back belts.

The research was conducted to evaluate the frequency of respiration during a repetitive lifting task when abdominal compression occurs from wearing a back belt. Three back belts were evaluated in this study: a nylon back belt, an inflatable back belt and an elastic vest. Analysis of the data revealed that the frequency of respiration increased while wearing the back belts at rest and while performing a repetitive lifting task. A statistically significant increase in the frequency of respiration was found while wearing the nylon back belt during the lifting task.

Abdomen↗

PubMed2002

Bax and heart mitochondria: uncoupling and inhibition of respiration without permeability transition.

The effects of Bax (full-length, FL, and C-terminal truncated, DeltaC) on respiration rate, membrane potential, MgATPase activity and kinetics of regulation of respiration were studied in isolated rat heart mitochondria and permeabilized cardiomyocytes. The results showed that while both Bax-FL and Bax-DeltaC permeabilized the outer mitochondrial membrane, released cytochrome c and reduced the respiration rate, the latter could be fully restored by exogenous cytochrome c only in the case of Bax-DeltaC, but not in presence of Bax-FL. In addition, Bax-FL but not Bax-DeltaC increased the MgATPase activity, and their effects on the mitochondrial membrane potential were quantitatively different. None of these effects was sensitive to cyclosporin A (CsA). It is concluded that Bax-FL affects both the outer and the inner mitochondrial membranes by: (1) opening large pores in the outer membrane; (2) inhibiting some segments of the respiratory chain in the inner membrane; and (3) uncoupling the inner mitochondrial membrane by increasing proton leak without opening the permeability transition pore (PTP).

Adenosine Diphosphate↗

PubMed1998

Optimization and mechanism of step-leap respiration exercise in treating of cor pulmonale.

The interaction between cardiovascular system and the respiratory system is complicated and may be used for the rehabilitation of the cor pulmonale disease. To study the effects of different breathing mode on the cardiac and pulmonary systems, a mathematical model is established based on the previous work. Using this model, computer simulation experiments are carried out for searching an optimal respiration mode in treating of cor pulmonale disease. Results indicate that the step-leap respiration mode could provide a better assistant to the rehabilitation of the cor pulmonale patients in the sense of increasing coronary flow, reducing pulmonary arterial pressure and reducing the working load for the right heart. This result is also proven by the clinical experiments. This work may suggest that a proper directed respiration exercise can be used in the treatment of cor pulmonale disease.

Algorithms↗

PubMed2001

Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply.

Oxygen limitation is generally considered as impairment of mitochondrial respiration under hypoxia and ischemia. Low intracellular oxygen levels under normoxia, however, imply mild oxygen limitation, provide protection from oxidative stress, and result from economical strategies for oxygen transport through the respiratory cascade to cytochrome c oxidase. Both perspectives relate to the critical oxygen pressure, which inhibits mitochondrial respiration. Based on methodological considerations of oxygen kinetics and a presentation of high-resolution respirometry, mitochondrial oxygen affinities (1/P(50)) are reviewed with particular emphasis on the turnover effect under control of adenosine diphosphate ADP concentration, which increases the P(50) in active states. ADP/O(2) flux ratios are high even under severe oxygen limitation, as demonstrated by calorespirometry. Oxygen limitation reduces the uncoupled respiration observed under control by ADP, as shown by relationships derived between ADP/O(2) flux ratios, respiratory control ratios, and ADP kinetics. Bioenergetics at low oxygen versus oxidative stress must be considered in the context of limitation of maximum aerobic activity, ischemia-reperfusion injury, mitochondrial signalling to apoptosis, and mitochondrial theories of ageing.

Adenosine Diphosphate↗

PubMed1998

Variability of vigilance and ventilation: studies on the control of respiration during sleep.

Ventilation is under metabolic as well as under behavioural control. This causes a complex interaction between states of 'vigilance' and respiration. This paper briefly summarizes sleep-related changes of respiration and presents an experimental study on the course of respiratory CO2-sensitivity during a whole night's sleep in ten healthy volunteers. The feedback control of breathing was challenged by continuous step changes of inspired CO2 every 7 min, resulting in 60, 3-step steady-state hypercapnic ventilatory responses (HCVR) per night in each subject. We analysed the variability of baseline ventilation and the effects of hypercapnia on ventilation with respect to sleep stages. There were only small differences in baseline PCO2 and ventilation between sleep stages, but a high variability of the slope of the CO2-response curves in the course of the night, ranging from 0.5 to 3.0 L min(-1) Torr(-1). The HCVR was significantly lower during REM sleep than during all stages of NREM sleep. Due to a compensatory left shift of the flattened CO2-response curves, however, ventilation at baseline CO2 as well as during slight hypercapnia varied much less than would be expected from the high variability of slopes. We conclude that the characteristics of the CO2-sensitive feedback control system of respiration, are highly variable during sleep, but due to offsetting effects, PCO2 and ventilation remain quite stable in the physiological range.

Adult↗

PubMed1998

Pharmacological properties of the CO2/H+-sensitive area in the ventral medullary surface assessed by the effects of chemical stimulation on respiration.

We recently discovered that CO2/H+-sensitive neurons in the ventral medullary surface (VMS) are immunoreactive to glutamate, glutamic acid decarboxylase (GAD), calcineurin and cAMP. We then tested the hypothesis that glutamate, GABA, calcineurin and cAMP affect the activity of CO2/H+-sensitive neurons in the VMS. Using male Wistar rats anesthetized with urethane and pentobarbital, we checked for changes in relative tidal volume (VT) and respiratory frequency (f) in response to injecting the VMS with a variety of test agents dissolved in mock CSF. Respiratory changes occurred immediately and were dose-dependent. (1) 200-1600 pmol Glutamate increased VT but decreased f. The glutamate effect was never abolished by concomitant injection of AP5, a NMDA receptor antagonist, but was abolished by CNQX, an AMPA receptor antagonist, indicating predominance of AMPA receptors in the CO2/H+-sensitive neurons in the VMS. (2) 200-1600 pmol GABA decreased both VT and f. The GABA effect was never abolished by concomitant injection of saclofen, a GABA(B) receptor antagonist, but was abolished by bicuculline, a GABA(A) receptor antagonist, indicating predominance of GABA(A) receptors in the CO2/H+-sensitive neurons in the VMS. (3) 4-32 microg Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase 2B, and 200-1600 pmol FK506, selective inhibitor of calcineurin, had no effect on respiration when they were applied extracellularly, but 400-3200 pmol BAPTA-AM, an intracellular Ca2+-chelating agent, decreased both VT and f, indicating involvement of intracellular Ca2+ in the excitatory mechanisms of respiration. (4) 100-800 pmol IBMX, an enhancer of intracellular cAMP, decreased both VT and f, indicating involvement of cAMP in the inhibitory mechanisms of respiration. These results indicate that the CO2/H+-sensitive neurons in the VMS contain glutamate and/or GABA in cytoplasma, possess AMPA and/or GABA(A) receptors on surface of plasma membrane, and compose the internal circuit, and that their activities are regulated by Ca2+ and cAMP.

1-Methyl-3-isobutylxanthine↗

PubMed1998

Neuronal apoptosis in rats is accompanied by rapid impairment of cellular respiration and is prevented by scavengers of reactive oxygen species.

Apoptosis of cerebellar granule cells induced by potassium withdrawal is accompanied by a very rapid decrease in both cell and mitochondrial respiration supported by glucose and succinate, respectively. The respiratory control ratio, which is an index of oxidative phosphorylation and therefore reflects the ability of mitochondria to produce ATP, is reduced by 50% within the first 2 h after the beginning of apoptosis, insulin-like growth factor I (IGF-I), actinomicin D or cycloheximide, previously reported to inhibit apoptosis, fully prevent the impairment of cellular respiration while scavengers of reactive oxygen species partially inhibit apoptosis and restore cellular respiration.

Animals↗

PubMed2003

Estimating uncertainties of the geometrical range of particle radiotherapy during respiration.

PURPOSE: To propose a method for estimating uncertainties of the range calculation in particle radiotherapy associated with patient respiration. MATERIALS AND METHODS: A set of sequential CT images at every 0.2 s was reconstructed from continuous X-ray projection data accumulated by dynamic helical scanning. At the same time that CT data was acquired, the respiratory signal of the patient and the X-ray on/off signal on CT scanner were recorded. Each CT image was timed according to the phase of respiration waveform. Conversion of the CT number to the water equivalent path length (WEL) was performed with our treatment planning system that included a conversion table. As an illustration, the CT images of a patient with liver cancer at the right upper lobe were analyzed. The geometric size of the liver and WELs from body surface to isocenter were measured in each CT image. RESULTS: Variations of WEL from body surface to isocenter at the anterior-posterior and posterior-anterior direction were 6.2 mm and 18.9 mm, respectively. Liver size changed by 35.2 mm. However, these variations were shown to be considerably reduced by gated irradiation. CONCLUSIONS: A method using sequential CT images with respiration waveform was proposed. It appeared to be useful in evaluating the uncertainties of the range calculation associated with patient breathing.

Artifacts↗

PubMed2002

Oxygen desaturation and heart rate variability due to Cheyne-Stokes respiration in congestive heart failure patients.

Cheyne-Stokes respiration is common in congestive heart failure patients and causes cyclical fluctuation of the RR interval. We studied the characteristics of apnea-related heart rate variability (apnea HRV) and the relation between apnea HRV and oxygen desaturation was examined. Ambulatory electrocardiograms and data on respiration (oronasal flow, tracheal sounds, abdominal wall movement and oxygen saturation) were simultaneously recorded by a multi-channel digital recorder for 16 congestive heart failure patients (10 men and 6 women; mean age, 68 +/- 13 years). HRV occurred as a result of cyclical apnea attacks between 0.005 and 0.03 Hz (apnea band). Apnea HRV was obtained as the power ratio of apnea HRV normalized by the very low frequency band (0.003-0.04 Hz). Apnea HRV increased with the number of apnea episodes and the oxygen desaturation index, but no relation between apnea HRV and either mean oxygen density or oxygen desaturation time was observed. We concluded that apnea HRV is a predictor of the number of apnea attacks or oxygen desaturation, but does not reflect the degree of oxygen desaturation in Cheyne-Stokes respiration.

Aged↗

PubMed1998

Inhibition of masseteric electromyographic activity during oral respiration.

Although the effects of oral respiration on the growth and development of craniofacial structure have been studied previously, little is known about how altered respiration affects the activity of the jaw-closing muscles. Obstruction of the nasal airway in the cat significantly inhibited the masseteric stretch reflex and discharges of masseteric motor units but did not affect the electromyographic activity of the diaphragm. This inhibition was greater during inspiration than during expiration. In addition, the amplitude of the masseteric monosynaptic reflex elicited by electrical stimulation of the mesencephalic trigeminal nucleus showed no significant change in association with the altered respiratory mode. These findings suggest that masseteric electromyographic activity is inhibited during oral respiration and that the gamma-system is involved in this inhibition.

Action Potentials↗

PubMed2000

In vivo control of respiration by cytochrome c oxidase in human cells.

The metabolic control of oxidative phosphorylation (OXPHOS) has attracted increasing attention in recent years, especially due to its importance for understanding the role of mitochondrial DNA mutations in human diseases and aging. Experiments on isolated mitochondria have indicated that a relatively small fraction of each of several components of the electron transport chain is sufficient to sustain a normal respiration rate. These experiments, however, may have not reflected the in vivo situation, due to the possible loss of essential metabolites during organelle isolation and the disruption of the normal interactions of mitochondria with the cytoskeleton, which may be important for the channeling of respiratory substrate to the organelles. To obtain direct evidence on this question, in particular, as concerns the in vivo control of respiration by cytochrome c oxidase (COX), we have developed an approach for measuring COX activity in intact cells, by means of cyanide titration, either as an isolated step or as a respiratory chain-integrated step. The method has been applied to a variety of human cell types, including wild-type and mtDNA mutation-carrying cells, several tumor-derived semidifferentiated cell lines, as well as specialized cells removed from the organism. The results obtained strongly support the following conclusions: (i) the in vivo control of respiration by COX is much tighter than has been generally assumed on the basis of experiments carried out on isolated mitochondria; (ii) COX thresholds depend on the respiratory fluxes under which they are measured; and (iii) measurements of relative enzyme capacities are needed for understanding the role of mitochondrial respiratory complexes in human physiopathology.

Animals↗

PubMed1996

Patient's experiences of communication during the respirator treatment period.

This paper reports a study of the patients' experiences of communication during the respirator treatment period (RT period) in the intensive care unit (ICU). This descriptive and exploratory study was designed to answer the question. How do respirator treated patients experience communication? Eight individuals who had experienced being treated with a respirator in two ICUs in Iceland, took part in audiotape-recorded, open interviews. They described their subjective experiences of communication during the RT period. The descriptions were analysed phenomenologically, using Colaizzi's method, described by Hycner (1985). The results revealed 57 themes within four categories, namely 'the patients' experiences of communication during the RT period', 'problems of communication experienced', 'additional problems of communication experienced' and 'nursing interventions experienced'. In this paper the themes within the categories of the patients' experiences of communication and problems of communication will be reported. The participants remembered their experience of communication clearly. The patients' experiences of communication were generally described as negative; they experienced communication as impaired, which evoked various negative emotions, and sometimes they had the feeling of giving up. Participants generally described being tired or exhausted during the intubation period. They emphasised the importance of the information and explanation provided by the nurses. The presence and support provided by family members was also valuable to them. The results add to the cumulative knowledge base of communication between nurses and patients by generating new meanings of the nature and essences of communication during the RT period from the patients' perspectives. In this article, the findings of the study are described and discussed in relation to earlier published research and clinical literature on the subject.

Adult↗

PubMed1997

Assessment of respiration during video fluoroscopy of dysphagic patients.

RATIONALE AND OBJECTIVES: The authors evaluated the coordination of swallowing and respiration in dysphagic patients. MATERIALS AND METHODS: Video fluoroscopy and respirometry were performed simultaneously during 98 swallows in 33 patients (18 women, 15 men) with a median age of 70 years (interquartile range, 52-78 years). Pharyngeal transit time, deglutition apnea, and the ratio between the two (swallowing safety index) were calculated. Presence of a misdirected swallow (aspiration or penetration) was indicated. RESULTS: Pharyngeal transit time was not associated with deglutition apnea. Misdirected swallow was associated with a slightly prolonged pharyngeal transit time, a slightly shorter deglutition apnea, and a significantly lower swallowing safety index (1.8 [1.0-4.2] vs 4.5 [2.4-6.7]; P < .001) compared with normally directed swallow. The association between misdirected swallow and lower swallowing safety index was independent of pharyngeal transit time. CONCLUSION: Assessment of respiration is important in the evaluation of dysphagia. Aspiration, especially in elderly dysphagic patients, may be a consequence of primarily disturbed respiration. A low swallowing safety index may indicate risk of misdirected swallow.

Aged↗

PubMedDate not supplied

Enhanced cellular respiration in cells exposed to doxorubicin.

Doxorubicin executes topoisomerase II mediated apoptosis, a process known to result in mitochondrial dysfunction, such as the leakage of cytochrome c and the opening of mitochondrial permeability transition pores (PTP). To further define the effects of doxorubicin on cell metabolism, we measured cellular respiration, cellular ATP, DNA fragmentation, and cytochrome c leakage in Jurkat (supersensitive), human leukemia-60 (HL-60, sensitive), and HL-60/MX2 (resistant) cells following exposure to 1.0 microM doxorubicin for 30 min. The measurements were made after 24 h of exposure to the drug. In Jurkat and HL-60 cells, doxorubicin treatment increased cellular mitochondrial oxygen consumption and ATP content by 2-3-fold. The increment in oxygen consumption was blocked by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone (zVAD-fmk) and by the PTP inhibitor cyclosporin A. In HL-60/MX2 cells, which are resistant because of a reduced topoisomerase II activity, doxorubicin treatment was without effect on either respiration or ATP content, suggesting that topoisomerase II was essential for induction of apoptosis and stimulation of respiration and ATP content. The conclusion that both of the latter processes were products of oxidations in the mitochondrial respiratory chain was supported by the further observation that rotenone and sodium cyanide inhibited oxygen consumption and substantially lowered ATP content in the treated and untreated cells. Thus, oxidative phosphorylation is enhanced in cells briefly incubated with doxorubicin for as long as 24 h post drug exposure despite apoptosis-associated mitochondrial insults caused by the drug.

Adenosine Triphosphate↗