Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure.
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Recent studies have suggested that the increased ventilatory response during exercise in patients with chronic heart failure was related to the activation of muscle metaboreceptors. To address this issue, 23 patients with heart failure and 7 normal subjects performed arm and leg bicycle exercises with and without cuff inflation around the arms or the thighs during recovery. Obstruction slightly reduced ventilation and gas exchange variables at recovery but did not change the kinetics of recovery of these parameters compared with nonobstructed recovery: half-time of ventilation recovery was 175 +/- 54 to 176 +/- 40 s in patients and 155 +/- 66 to 127 +/- 13 s in controls (P < 0.05, patients vs. controls, not significant within each group from baseline to obstructed recovery). We conclude that muscle metaboreceptor activation does not seem to play a role in the exertion hyperventilation of patients with heart failure. (+info)
S-nitrosoglutathione enhances neutrophil DNA fragmentation and cell death.
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Enhancing the clearance of neutrophils by enhancing apoptotic cell death and macrophage recognition may be beneficial in acute lung injury. Exogenous nitric oxide gas depresses neutrophil oxidative functions and accelerates cell death (A. H. Daher, J. D. Fortenberry, M. L. Owens, and L. A. Brown. Am. J. Respir. Cell Mol. Biol. 16: 407-412, 1997). We hypothesized that S-nitrosoglutathione (GSNO), a physiologically relevant nitric oxide donor, could also enhance neutrophil DNA fragmentation. Neutrophils were incubated for 2-24 h in the absence and presence of GSNO (dose range 0.1-5 mM) and evaluated for cell death by a fluorescent viability/cytotoxicity assay. Neutrophil DNA fragmentation was assessed by cell death detection ELISA and by terminal deoxynucleotidyltransferase-mediated fluorescence-labeled dUTP nick end labeling assay. Neutrophil oxidative function was also determined. Incubation with GSNO increased cell death at 2, 4, and 24 h. GSNO incubation for 24 h significantly increased DNA fragmentation in a dose-dependent fashion at 0.5 (median 126% of control value; P = 0.002) and 5 mM (185% of control value; P = 0.002) by terminal deoxynucleotidyltransferase-mediated fluorescence-labeled dUTP nick end labeling and at 0.5 mM by ELISA (164% of control value; P = 0.03). The apoptosis-to-total cell death ratio increased with increasing GSNO concentration (P < 0.05). Effects were mitigated by coincubation with superoxide dismutase. Five millimolar GSNO decreased overall superoxide generation and O2 consumption but not when adjusted for dead neutrophils. GSNO significantly enhances cell death and neutrophil DNA fragmentation in a dose-dependent fashion. (+info)
Skeletal muscle tissue oxygen pressure distribution during early reperfusion after prolonged ischaemia.
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OBJECTIVES: The aim of this study was to investigate the skeletal muscle tissue oxygen pressure (PtO2) distributions during early reperfusion (10-45 min) after prolonged ischaemia in a rat animal model. MATERIAL AND METHODS: Skeletal muscle ischaemia was induced in anaesthetised rats by applying a tourniquet on the left thigh for 3 h (group I) or 4 h (group II), and tissue oxygen pressure measurements were made after 10-45 min of reperfusion. Assessment of PtO2 was made by a multiwire Clark-type oxygen microelectrode, placed on the surface of the left tibialis anterior muscle. RESULTS: During reperfusion a similar PtO2 pattern was evaluated after both 3 and 4 h of total ischaemia, where the sum PtO2 distributions were shifted to the left associated with low tissue oxygen pressure values. After 10 min of reperfusion the median PtO2 was 0.28 kPa and 0.18 kPa, in groups I and II, respectively; after 45 min of reperfusion 0.61 kPa and 0.60 kPa, respectively. The median PtO2 in the non-ischaemic muscle in groups I and II were 2.19 and 2.17 Pa. CONCLUSION: The results show that local skeletal muscle oxygenation is severely impaired during the initial 45 min of reperfusion after both 3 and 4 h of total muscle ischaemia with a slow-reflow phenomenon generally present, despite pronounced needs. (+info)
Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity.
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Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia. (+info)
Bioelectrical impedance plethysmographic analysis of body composition in critically injured and healthy subjects.
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BACKGROUND: Determination of body composition during critical illness is complex because of various patient-related and technical factors. Bioelectrical impedance is a promising technique for the analysis of body composition; however, its clinical utility in critically injured patients is unknown. OBJECTIVE: The purpose of this study was to compare bioelectrical impedance with metabolic activity in healthy and critically injured patients. If bioelectrical impedance accurately determines body composition during critical illness, the slope between body-composition variables and oxygen consumption would be the same in critically injured and healthy subjects. DESIGN: There is a strong linear relation between body composition and metabolic activity. In the present study, body composition (fat-free mass and body cell mass) was determined by using bioelectrical impedance and resting metabolic activity (metabolic rate and oxygen consumption) by using gas exchange analysis in a group of healthy and critically injured subjects. The relation between these variables was compared by using linear regression to a similar relation established by hydrostatic weighing in a large historical control group. RESULTS: The slope of the line relating fat-free mass to resting metabolic rate was the same in the healthy and critically ill groups (P = 0.62) and each was similar to the slope of the line for the control group. However, in 37% of the critically injured group, overhydration contributed to an increase in fat-free mass, disturbing the relation with resting metabolic rate. The slope of the line relating body cell mass to oxygen consumption in our healthy and critically ill groups was almost identical. CONCLUSION: These results support the use of bioelectrical impedance to determine body cell mass in healthy and critically ill subjects. (+info)
Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange.
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Growth factor withdrawal is associated with a metabolic arrest that can result in apoptosis. Cell death is preceded by loss of outer mitochondrial membrane integrity and cytochrome c release. These mitochondrial events appear to follow a relative increase in mitochondrial membrane potential. This change in membrane potential results from the failure of the adenine nucleotide translocator (ANT)/voltage-dependent anion channel (VDAC) complex to maintain ATP/ADP exchange. Bcl-xL expression allows growth factor-deprived cells to maintain sufficient mitochondrial ATP/ADP exchange to sustain coupled respiration. These data demonstrate that mitochondrial adenylate transport is under active regulation. Efficient exchange of ADP for ATP is promoted by Bcl-xL expression permitting oxidative phosphorylation to be regulated by cellular ATP/ADP levels and allowing mitochondria to adapt to changes in metabolic demand. (+info)
Brief vibrotactile stimulation does not increase cortical oxygen consumption when measured by single inhalation of positron emitting oxygen.
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Vibrotactile stimulation of the hand elicits no increase in oxygen consumption commensurate with the increase in blood flow measured in human sensory cortex. To test the hypothesis that previous failures to detect a proportionate increase in oxygen consumption could be an artefact of the sequential bolus, or three-step, method used to measure this parameter in the human brain in vivo, the authors compared the measurements with the results of a novel single bolus, or one-step, method of measuring oxygen consumption. The time of completion of the three-step method was 40 to 50 minutes, whereas the one-step method lasted only 3 minutes. The baseline whole-brain oxygen consumption averaged 185 +/- 32 micromol hg(-1) min(-1) by the three-step method and 153 +/- 15 micromol hg(-1) min(-1) by the one-step method. Vibrotactile stimulation did not elicit a significant increase in oxygen consumption measured by either method. This finding rejects the hypothesis that failure to detect an increase of oxygen consumption could be an artefact caused by limitations of the method used previously. Conversely, it also rejects the hypothesis that observations of an increase of oxygen consumption by the new method are artefacts caused by limitations of the one-step method. (+info)
Oxygen consumption of cerebral cortex fails to increase during continued vibrotactile stimulation.
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The coupling of oxidative metabolism to the blood flow of the sensory motor hand area is uncertain. The authors tested the hypothesis that continued vibrotactile stimulation ultimately must lead to increased oxygen consumption consumption. Twenty-two healthy right-handed young volunteers underwent positron emission tomography (PET) with the [(15)O]water bolus injection method to measure water clearance (K1H2O an index of blood flow (CBF), and with the [(15)O]oxygen bolus inhalation method to measure CMR(O2). The CMR(O2) was measured 30 seconds and 20 minutes after onset of intermittent (1 second on, 1 second off) vibrotactile stimulation (110 Hz) and compared with baseline measurements without stimulation. The K1H2O and CMR(O2) changes (delta K1H2O and delta CMR(O2)) were determined using intersubject averaging, together with magnetic resonance imaging based stereotaxic registration technique. The K1H2O increase was 21 +/- 4% and 12 +/- 4% at 30 seconds and 20 minutes after onset of stimulation, respectively. No significant increase of CMR(O2) was found until 30 minutes after the onset of stimulation. The authors conclude that blood flow and oxidative metabolism undergo uncoupling during sustained phasic stimulation of the sensory hand area. Therefore, neuronal activity stimulated in this manner does not rely on significantly increased oxidative phosphorylation. (+info)