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Biomedical subjects

B Chance

Publications and source records attributed to B Chance.

At least 217 records · Page 12Linked to original sources

Time resolved spectroscopic (TRS) and continuous wave spectroscopic (CWS) studies of photon migration in human arms and limbs.

The combination of continuous light spectrophotometry (CWS) and time resolved spectrophotometry (TRS) afford for the first time a quantitation of the optical path and the concentration changes detected by the CWS instrument. The application of these two techniques and magnetic resonance spectroscopy (MRS) to muscle during exercise affords a correlation of the biochemical activation and the response of the peripheral circulation (NRS) to the exercise stress (MRS). In preliminary experiments, the well-trained endurance performance limb shows a near perfect homeostasis to exercise stress while ischemia will cause a significant deoxygenation and an impairment of the work output. The use of this device in evaluation of peripheral vascular disease is obvious and hemoglobin deoxygenation may well occur at work levels less than those at which the diseased limb is capable.

Arm↗

Wrist flexor muscles of elite rowers measured with magnetic resonance spectroscopy.

We used phosphorus magnetic resonance spectroscopy to study skeletal muscle metabolism of trained vs. untrained humans. The forearms of highly trained rowers (n = 10) and age-matched controls were placed in a 1.9-T magnet so that the wrist flexor muscles were placed over a 4-cm transmitting and receiving coil. The subjects performed work by depressing a handle attached to an isokinetic ergometer. Relative concentrations of Pi, phosphocreatine (PCr), and ATP were measured along with intracellular pH. Measurements were made at rest, during steady-state and ramp exercise protocols, and during recovery from exercise. At rest the rowers had Pi/PCr that were not different from control. During steady-state exercise rowers (n = 4) had lower Pi/PCr at the same relative power levels, and the slope of the power vs. Pi-PCr curve was significantly greater than for controls. Rowers (n = 4) also had faster rates of PCr recovery after exercise than controls (T1/2 of 24 +/- 2.0 s for rowers and 47 +/- 8.4 s for controls) when power level was adjusted so that all subjects recovered from the same level of Pi/PCr. During a ramp exercise protocol, the initial slope of the power vs. Pi-PCr curve was greater in three of six rowers compared with controls and at the highest power level rowers had lower Pi/PCr values with less drop in pH. At the end of the ramp test, the same degree of muscle fatigue was associated with much lower levels of H2PO-4 (5.7 +/- 0.70 mM) in rowers compared with controls (13.0 +/- 1.8 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Effects of ovariectomy on energy metabolism in exercising rat muscle studied by 31P-NMR.

The effects of ovariectomy on metabolism of high-energy phosphate compounds during and after exercise were studied in hindleg muscles of 14 rats. Sciatic nerve stimulation was used to establish different work loads, and the changes in inorganic phosphate-to-phosphocreatine ratios (Pi/PCr) were recorded by 31P nuclear magnetic resonance (NMR) in vivo. Four weeks after ovariectomy, there was evidence of significantly higher Pi/PCr during work at stimulation rates greater than 0.5 Hz. The slope for the stimulation rate-to-Pi/PCr relationship decreased from 1.98 +/- 0.15 to 1.36 +/- 0.2 Hz/Pi/PCr after ovariectomy. The normalized tension output of these muscles, tested separately using identical stimulation protocols, was not changed with ovariectomy. Thus the relationship between work (tension-time integral) and bioenergetic cost (Pi/PCr) suggested reduced maximal enzyme activity (Vmax) by 9-17% as a result of lack of ovarian sex hormones, but no change in Michaelis-Menten constant (Km) was found. Postexercise recovery was also significantly slower (3.27 +/- 0.54 PCr/Pi units per minute compared with 4.04 +/- 1.08 in controls). It is suggested that reduced levels of ovarian sex hormones decrease oxidative phosphorylation. Cytochrome oxidase activity was reduced in these muscles by 40%, but other mitochondrial enzyme systems may be affected as well. The possible significance of these data is the implication of a reduced capacity for menopausal women or amenorrheic female athletes to perform prolonged intensive exercise.

Adenosine Triphosphate↗

In vivo myocardial bioenergetics during acute volume and/or pressure loading in a canine model: a 31P NMR study.

The effects of acute volume and/or pressure loading on myocardial metabolic and mechanical function were studied in 13 dogs. Volume loads were applied by shunting the abdominal aorta to the vena cava using polyethylene tubing (5 mm inner diameter). A plastic regulator allowed shunts to be opened or closed. Dogs were heparinized (100 units/kg) to prevent shunts from clotting. To study the effects of pressure loading, a norepinephrine infusion (1 microgram/kg/min) was administered. Mechanical function of the heart was evaluated using heart rate X systolic blood pressure (HR X SBP), cardiac output (CO), pressure X volume work (systolic blood pressure X stroke volume); (P X V), and oxygen consumption (MVO2) to estimate external myocardial work. Metabolic function was evaluated by 31P NMR. Phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were used to estimate the bioenergetic regulation of oxidative phosphorylation during increased work load. HR X SBP, CO, P X V, and MVO2 were correlated with PCr/ATP. Although there was some variability, generally volume loading was associated with an increase in HR X SBP, CO, P X V, and MVO2 accompanied by no change, or small increases or small decreases in PCr/ATP throughout the loading period. These data indicate that the heart bioenergetics are quite stable during volume and/or pressure loading and that 31P spectroscopy methods can document this stability and tight metabolic regulation during in vivo loading conditions.

Adenosine Triphosphate↗

Noninvasive detection of skeletal muscle underperfusion with near-infrared spectroscopy in patients with heart failure.

The present study was undertaken to determine whether near-infrared spectroscopy can be used to noninvasively assess skeletal muscle oxygenation in patients with heart failure. The difference between light absorption at 760 and 800 nm was used to assess hemoglobin-myoglobin oxygenation. Initial studies conducted in isolated canine gracilis muscle demonstrated that 760-800-nm absorption correlated closely (r = -0.97 +/- 0.01) with venous hemoglobin O2 saturation when the muscle was stimulated to contract at 0.25-5.0 Hz. In normal subjects (n = 6) and patients with heart failure (n = 8), 760-800-nm absorption changes from the vastus lateralis muscle were monitored at rest, during progressive maximal bicycle exercise, and during thigh cuff inflation to suprasystolic pressure, an intervention designed to assess minimal hemoglobin-myoglobin oxygenation. Absorption changes were expressed relative to the full physiologic range noted from rest to thigh cuff inflation. During exercise, normal subjects exhibited an initial increase in hemoglobin-myoglobin oxygenation followed by a progressive decrease in oxygenation to 27 +/- 13% of the physiologic range at the peak exercise workload of 140 +/- 9 W. In contrast, patients exhibited an initial decrease in hemoglobin-myoglobin oxygenation with the first workload, followed by a progressive further decrease to 26 +/- 13% of the physiologic range at a peak exercise workload of 60 +/- 8 W, less than half the peak workload noted in the normal subjects. At all exercise loads, hemoglobin-myoglobin oxygenation was significantly less in the patients than in the normal subjects. These data suggest that near-infrared spectroscopy can detect impaired skeletal muscle O2 delivery in patients with heart failure. This technique could provide a valuable method of assessing muscle O2 delivery in patients, particularly before and after therapeutic interventions.

Animals↗

Compartment syndrome: a quantitative study of high-energy phosphorus compounds using 31P-magnetic resonance spectroscopy.

The purpose of this study was to quantitate the intracellular high-energy phosphate compounds during 6 hours of tissue ischemia in the anterior tibial compartment of beagles subjected to an induced traumatized compartment syndrome. The goal of this work was to provide clinicians with objective criteria to augment clinical judgment regarding surgical intervention in the impending compartment syndrome. A beagle model was utilized in which the Delta pressure (difference between the mean arterial pressure and compartment pressure) could be controlled. The model, in conjunction with 31P-magnetic resonance spectroscopy (MRS), allowed a measure of high-energy phosphate compounds and pH in the compartment at various Delta pressures. The extent of ischemic metabolic insult in the compartment was then quantitated. Our data suggest the following: 1) lower Delta pressures result in a proportionally greater drop in the intracellular phosphocreatine ratio and pH; 2) at lower Delta pressures, there is proportionally greater decline in the percentage recovery post-fasciotomy; 3) blood pressure is extremely important and periods of hypotension may result in increased muscle damage at lower compartment pressures.

Animals↗

Muscle injury and exercise stress measured with 31-P magnetic resonance spectroscopy.

In conclusion, MRS is a noninvasive method of measuring high energy compounds in resting and exercising human muscle. We found that high levels of work were required to detect significant differences in muscle metabolism. Large variations were seen between control subjects. Endurance athletes had muscles with better oxidative metabolism than the control subjects. By looking carefully at resting metabolism we were able to detect and monitor the level of exercise-induced muscle injury. Finally we were able monitor in a temporal manner changes in muscle metabolism which occur with endurance training and detraining in control subjects.

Athletic Injuries↗

Detection of abnormal calf muscle metabolism in patients with heart failure using phosphorus-31 nuclear magnetic resonance.

Patients with heart failure frequently report leg fatigue during exercise. At present, however, there is no objective method of detecting leg muscle abnormalities in such patients. To determine if phosphorus-31 nuclear magnetic resonance spectroscopy can provide such information, this technique was used to compare calf responses to stair climbing and plantarflexion in 20 patients with heart failure (peak oxygen consumption (VO2) of 13.6 +/- 5 ml/kg/min, ejection fraction 20 +/- 5%) and 9 age-matched normal subjects. Work was quantified by measuring VO2. At rest, both groups exhibited similar inorganic phosphorus to phosphocreatine (Pi/PCr) ratios (patients with heart failure 0.21 +/- 0.07, normal subjects 0.21 +/- 0.06, difference not significant) and pH levels (patients with heart failure 7.06 +/- 0.17, normal subjects 7.05 +/- 0.11, difference not significant). In both normal subjects and patients with heart failure, exercise resulted in a progressive rise in Pi/PCr as VO2 increased. However, examination of the relation of VO2 versus Pi/PCr revealed steeper slopes in patients with heart failure during both stair climbing and plantar-flexion. Neither form of exercise decreased calf pH in normal subjects. In the patients with heart failure, significant decreases in pH were noted during the highest work level of plantarflexion (pH of heart failure patients 6.86 +/- 0.20, pH of normal subjects 7.07 +/- 0.14, p less than 0.01). Metabolic recovery time was also prolonged in the patients with heart failure versus normal subjects (3.3 +/- 0.8 vs 2.1 +/- 0.5 minutes, respectively, p less than 0.002). These findings indicate that phosphorus-31 nuclear magnetic resonance provides objective evidence of leg muscle abnormalities in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Time-resolved spectroscopy of hemoglobin and myoglobin in resting and ischemic muscle.

Difficulties of quantitation of hemoglobin/myoglobin absorption changes in muscle have led to the development of a new approach using short pulses of light. This method uses input light pulses sufficiently short so that the time course of travel of light through the brain can be precisely measured. The time of arrival of light at the detector gives the optical path length, given the velocity of light in tissues. The intensity profile of photon migration in tissues permits determination of the path length that the exiting photons have traveled and the concentration change of the pigments. A cavity-dumped liquid dye laser illuminates the tissue with 130-ps pulses detected as 600-ps duration at a half height at 3.0-cm distance from the input point. The decay of intensity from the 50% point onward to 0.1% follows a logarithmic function of slope mu which is attributed to the total absorption coefficient of the tissue. Increments of mu due to deoxyhemoglobin absorption at 760 and 630 nm are used to calculate the concentration change. This permits the calculation of the path length for continuous light measurements of 2 cm for a particular geometry. Variation of the wavelength of the laser affords determination of a spectrum of changes in the tissue.

Adult↗

On the environment of zinc in beef heart cytochrome c oxidase: an x-ray absorption study.

The role of zinc in beef heart cytochrome c oxidase has been studied by using x-ray absorption spectroscopy, zinc depletion and secondary structure predictions of subunits of beef heart cytochrome c oxidase. The stoichiometry of zinc in cytochrome oxidase has been determined in 35 different preparations and found to be one-half of copper (Cu:Zu = 2:1). Zinc is tightly bound to this enzyme and cannot be removed by dialysis against EDTA. However, zinc could be partially (up to 50%) depleted by treating the enzyme with either dipicolinic acid or by trypsin digestion. This partial depletion of zinc does not change the O2 uptake rate. X-ray absorption spectroscopy shows that the atom is in a distorted tetrahedral environment with mostly sulfur ligands. Since subunit VIa removed by the digestion removes about one-half the zinc, a possible binding site involves the two S sites present in that subunit with an appropriate folding in a structural role.

Animals↗

Does the peroxide compound of cytochrome oxidase contain a ferryl iron?

The reaction of peroxide with cytochrome oxidase generates a peroxide compound having a Soret maximum at 428 nm. X-ray absorption spectroscopy analysis of the local structure of the active site iron shows marked similarity to that of the cytochrome c peroxidase intermediate Compound ES, which contains a short iron to proximal nitrogen distance compared to globins. Reductive titration of the 580 nm band of this compound indicates that the iron is one oxidizing equivalent above the resting oxidized form. These results support the presence of a ferryl iron (Fe(IV) = O) in the peroxide compound similar to that found for the peroxidases.

Animals↗

Early reduction of cytochrome c in hypoxia.

Shifts of the steady state of cytochromes a, a3 and c at high pO2 values are cited as evidence of the low O2 affinity of cytochrome oxidase in vivo [(1971) Brain Res. 108, 143-154; (1985) Adv. Exp. Med. Biol. 191, 833-842; (1987) in: Int. Soc. Oxygen Transp. Tissue, Sapporo, p. 84]. Highly aerobic, small diploid yeast cells show less than 0.44% change of steady state in the interval prior to an abrupt reduction of cytochrome c. Thus, 'pre-reduction' seems falsified as a physiological response of metabolizing yeast cells that are free of hemoglobin, do not aggregate and maintain a steady state. Pre-reduction may be due to spectroscopic interference, for example hemoglobin deoxygenation, to oxygen gradients in aggregated cells and tissues or to non-steady states of substrate and metabolic controls, as contrasted to an altered cytochrome oxidase oxygen affinity in vivo.

Aerobiosis↗

In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis.

High-energy phosphate metabolism in skeletal muscle is altered during sepsis, although the chronology of events is uncertain. Phosphorus 31 magnetic resonance spectroscopy was used to measure changes in muscle energy stores of the left hind limb musculature of adult male rats during sepsis. Following control scans, cecal ligation and puncture were performed and scanning was repeated 6, 24, and 48 hours after surgery. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), a measure of energy stores, and adenosine triphosphate (ATP) to Pi ratio, a measure of the energy available for immediate use, were determined from peak heights. Intracellular pH was calculated using the distance between Pi and PCr peaks. In surviving animals, a 40% decrease in PCr/Pi ratio (+/- SEM) was observed by 24 hours (22.3 +/- 3.0 at time 0 vs 13.3 +/- 2.8 at 24 hours), whereas energy availability (beta-ATP/Pi) was statistically unchanged (18.2 +/- 2.2 at time 0 vs 15.2 +/- 1.2 at 48 hours). Intracellular pH did not change. Both PCr/Pi and ATP/Pi ratios were inversely correlated with time. In this model of documented peritonitis, skeletal muscle energy metabolism is rapidly altered following severe infection, and these changes can be detected using 31P magnetic resonance spectroscopy.

Adenosine Triphosphate↗

Triple nuclear NMR studies of cerebral metabolism during generalized seizure.

Noninvasive NMR spectroscopy of 1H, 31P, and 23Na is performed simultaneously to study brain metabolism during grand mal seizures. Decreases in PCr and increases in lactate associated with seizure as well as an intracellular shift of the Na+ ion pool are demonstrated. A close correlation between the phosphate potential and the intensity of the seizure, as well as the intra/extracellular ionic gradient, is shown.

Adenosine Diphosphate↗