Daisaku Kurita

Effects of age on muscle energy metabolism and oxygenation in the forearm muscles

PURPOSE The effects of aging on muscle metabolism and oxygenation have not yet been elucidated. We evaluated the effects of aging on energy metabolism and oxygenation in sedentary healthy subjects by simultaneously measuring 31P-magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS). METHODS Nine young (28.1 +/- 5.0 yr) and nine older (61.4 +/- 4.6 yr) healthy subjects were studied. The 31P-MR spectrum was obtained every 15 s during and after hand gripping exercise. Intracellular pH (pHi) and PCr/(PCr+Pi) [PCr: phosphocreatine, Pi: inorganic phosphate] were calculated as an index of energy metabolism. The time constant of the PCr/(PCr+Pi) recovery (tau PCr) was calculated. With NIRS, we evaluated the recovery rates of oxygenated (RHbO2) and deoxygenated hemoglobin (RHb) during the initial 10 s of recovery. RESULTS The PCr/(PCr+Pi) and pHi at rest and at completion of the exercise and tau PCr did not differ between young and older subjects. However, RHbO2 and RHb were significantly slower in older subjects than in young subjects. CONCLUSIONS The results suggest that muscle energy metabolism in the forearm muscle was not affected by aging. The slower RHbO2 and RHb in older subjects suggested impaired O2 supply, which was probably due to impaired peripheral circulation caused by the process of aging.

Liposome-Encapsulated Hemoglobin Alleviates Brain Edema After Permanent Occlusion of the Middle Cerebral Artery in Rats

Liposome-encapsulated hemoglobin (LEH) was proven to be protective in cerebral ischemia/reperfusion injury. The present study evaluated LEH in a rat model of permanent middle cerebral artery (MCA) occlusion to clarify its effect during ischemia and reperfusion. Five minutes after thread occlusion of the MCA, rats were infused with 10 mL/kg of LEH (LEH, n = 13), and compared with normal controls (n = 11). Additional animals received the same MCA occlusion with no treatment (CT, n = 11), saline (saline, n = 10), empty liposome solution (EL, n = 13), or washed red blood cells (RBC, n = 7). Severity of brain edema was determined 24 h later by signal strength in T2-weighted magnetic resonance imaging of the cortex, striatum, hippocampus, and pyriform lobe. The results showed that brain edema/infarction observed in any vehicle-infused control was significantly more severe than in LEH-treated rats. There was a tendency toward aggravated edema in rats receiving ELs. LEH infusion at a dose of 10 mL/kg significantly reduced edema formation as compared to other treatments in a wide area of the brain 24 h after permanent occlusion of the MCA. Low oncotic pressure of EL and LEH solution (vehicle solution) appeared to cause nonsignificant aggravation of edema and reduced protective effects of LEH.

Early damage to lung tissue after irradiation detected by the magnetic resonance T2 relaxation time.

We sought to determine whether nuclear magnetic resonance relaxation times of water in tissue would be useful to detect molecular damage in lung tissue within 2 weeks after irradiation. Tissue samples were obtained from the lungs of rats at various times between 1 and 14 days after exposure of a hemithorax to 20 Gy 60Co gamma irradiation. The spin-lattice relaxation time, T1, was measured by the inversion recovery method, and the spin-spin relaxation time, T2, was measured by both the Hahn spin-echo (Hahn T2) and the Carr-Purcell-Meiboom-Gill (CPMG T2) methods. The T2 of lung tissue could be divided into two components, T2 fast (T2f) and T2 slow (T2s), which reflected changes in the intracellular and extracellular water, respectively. The CPMG T2f increased significantly 3 days after irradiation (66.3 +/- 2.3 ms compared to 60.8 +/- 2.6 ms), and the CPMG T2s increased significantly 1 day after irradiation (155 +/- 11 ms compared to 138 +/- 7 ms), prior to the observation of abnormalities upon examination of the lung by light microscopy. The CPMG T2 values increased further up to 14 days after irradiation when significant increases were observed in values for T1, Hahn T2 and water content. Our results indicate that the molecular derangement in irradiated lung tissue was detected by the CPMG T2 measurement in the very early stage, and that MRI may be superior to conventional radiographs for detecting the early damage to lung tissue after irradiation.

Sequential changes in MR water proton relaxation time detect the process of rat brain myelination during maturation.

For better understanding of the behavior of water molecules in the animal brain, changes in magnetic resonance water proton relaxation processes were studied in the rat during maturation. Midbrains of male Wistar rats were removed at various time points ranging from 2 to 70 days after birth. Changes in relaxation time (water proton longitudinal relaxation time by the inversion recovery, and water proton transverse relaxation time by the spin echo and the Carr-Purcell-Meiboom-Gill pulse sequence (CPMG)) and water content were then determined for various stages of brain development. During maturation both water proton longitudinal relaxation time and water proton transverse relaxation time values decreased and this finding paralleled the decline in water content. Using the CPMG pulse sequence, the transverse relaxation time values were observed to separate into two components after 21 days. Morphologically, the most prominent change at the matured stage of midbrain development in the rat is myelination. Water proton relaxation time, which can be estimated using the CPMG pulse sequence, showed a close correlation with myelination in the central nervous system.

Time domain reflectometry: measurement of free water in normal lung and pulmonary edema

The free water content of lung tissue was investigated by dielectric spectroscopy in normal lungs and in pulmonary edema induced by oleic acid in rats. The dielectric relaxation in a frequency range of 107 to 1010 Hz was measured with the time domain reflectometry method at 25°C. Three dielectric relaxation processes were analyzed for the lung tissue. A high-frequency process around 10 GHz was attributed to the orientation of free water molecules based on the relaxation time [log τh (in s) = -11.03]. The dielectric strength (Δε) of this high-frequency peak (Δεh) should reflect the amount of free water in the tissue. Because the measured Δεh depended on the air content of the lung samples, the value of Δεh was corrected for the air content of each sample as determined by the point-counting method in the area where the time domain reflectometry data were obtained. The lungs of rats that received an injection of oleic acid had a significantly increased free water content [(Δεh of lung/Δε of pure water) × density of pure water] compared with that in the normal lung (0.76 vs. 0.59 g/cm3). These results indicate that free water occupies ∼60% of the total volume of normal lung tissue and that there is an increase in free water in pulmonary edema.

Plasma branched-chain amino acid levels and muscle energy metabolism in patients with chronic obstructive pulmonary disease

BACKGROUND & AIMS Although several studies have shown that plasma concentrations of branched-chain amino acids (BCAAs) are reduced in patients with chronic obstructive pulmonary disease (COPD), little is understood about how low concentrations of BCAAs limit exercise in such patients. The present study investigated whether plasma BCAAs are related to energy metabolism in exercising muscle using (31)P-magnetic resonance spectroscopy (MRS). METHODS We analyzed the plasma amino acid profiles of 23 male patients with COPD (aged 69.2+/-5.1 years) and of 7 healthy males (aged 64.1+/-6.0 years). We normalized the exercise intensity of repetitive lifting by adjusting the weight to 7% of the maximal grip power. The intracellular pH and the phosphocreatine (PCr) index (PCr/(PCr+Pi); Pi, inorganic phosphate) were calculated from MR spectra. We evaluated the relationship between intracellular pH and PCr index at the completion of exercise and the plasma BCAA concentration. RESULTS Glutamine concentrations were elevated in patients with COPD compared with healthy individuals. Plasma concentrations of BCAAs correlated with intracellular pH and PCr index at the completion of exercise. CONCLUSIONS The findings are consistent with the notion that BCAAs affect muscle energy metabolism during exercise in patients with COPD.

Distribution of brain oedema in the contralateral hemisphere after cerebral infarction: repeated MRI measurement in the rat

The appearance of local cerebral dysfunction at remote regions from the focus in the acute stage of stroke (diaschisis) is well known, but its mechanism has not been established. We have analysed serial MR images of the infarcted brain of rats to evaluate the distribution of oedema. Forty-seven Sprague-Dawley rats were anaesthetized with halothane, and the right middle cerebral artery (MCA) was permanently occluded via the intraluminal approach using a nylon 2-0 suture. At 3, 6, 9 and 24 hours after the occlusion, coronal T(2)-weighted MR images were taken and the signal intensity (SI) was computed at each region of the brain. After occlusion of the right MCA, SI increased diachronically up to 24 hours on the occluded side of the cortex (52.9+/-3.2 to 104.8+/-22.4) and striatum, which are within the perfusion territory of the MCA. SI increment was also observed at the hippocampus, alveus hippocampi and pyriform lobe, which are not within the territory of the MCA, and at some regions of the contralateral side (52.5+/-4.8 to 69.4+/-14.8 at the cortex). These changes were prominent in ischaemia-vulnerable portions, mild in the cortex, and minimal in the striatum. This contralateral side SI increment indicates remote oedema, which corresponds to diaschisis. We suggest that the mechanism of this remote contralateral oedema is the movement of extravasated protein from the lesion.

Muscle metabolism in patients with polymyositis simultaneously evaluated by using 31P‐magnetic resonance spectroscopy and near‐infrared spectroscopy

Summary Simultaneous measurements of muscle energy metabolism using 31P‐magnetic resonance spectroscopy (31P‐MRS) and the kinetics of muscular oxygen metabolism using near‐infrared spectroscopy (NIRS) were conducted in polymyositis (PM) patients. The subjects were 12 PM patients (age 45 ± 12 years) and 12 normal controls (age 41 ± 12 years). The muscle phosphocreatine (PCr) index and intracellular pH (pHi) were determined with 31P‐MRS and the changes in intramuscular oxygenated (oxy‐Hb), deoxygenated (deoxy‐Hb), and total haemoglobin (total Hb) were evaluated with NIRS . The pHi and PCr index before steroid therapy in PM patients were significantly lower during exercise than in normal controls, and their recovery was statistically significantly delayed compared with the controls. The pattern of changes in NIRS over time before steroid therapy in PM patients differed from that in normal controls. There were smaller changes in deoxy‐Hb and oxy‐Hb during exercise, and total Hb decreased during exercise. In contrast, the kinetics of muscular metabolism after steroid therapy showed changes similar to those seen in normal controls. Simultaneous 31P‐MRS and NIRS measurements to determine the kinetics of muscular metabolism are expected to be useful as a noninvasive approach for the evaluation of treatment effects in PM patients.

Magnetic resonance relaxation times in acute hydrostatic pulmonary edema induced by noradrenaline in rats.

Models of pulmonary edema have been used to study the nuclear magnetic resonance (NMR) characteristics of lung water. Several investigators have measured changes in the relaxation times in the permeability type of pulmonary edema, but relatively few have measured relaxation times in the hydrostatic type of pulmonary edema. In this study we determined the characteristics of NMR relaxation times T1, T2 (Hahn spin-echo decay) and water content in acute hydrostatic pulmonary edema induced by noradrenaline administration in rats. Changes in T1 and T2 showed a significant prolongation in hydrostatic pulmonary edema. T2 decay curves for peripheral lung tissues were muldexponential and fit two components [T2 fast (T2f) and T2 Slow (T2s) ]. With two-component T2 analysis, T2s showed greater prolongation than did T2f. The increase in T2s was significantly correlated with an increase in water content, but the increase in the T2f value was not correlated with water content or with a change in T2s. The T2s component, which likely reflected changes in interstitial water, was more closely related than the T2f component to an increase in water content in hydrostatic pulmonary edema. Results suggested that regional changes in hydrostatic pulmonary edema may be evaluated by multicomponent T2 analysis.

Effect of Glutamate and Its Antagonist on Shift of Water from Extra- to Intracellular Space After Cerebral Ischaemia

The effects of glutamate and the excitatory amino acid antagonist, MK-801, were investigated on the time course of the shift of water from extracellular to intracellular space (progression or cytotoxic oedema) after total brain ischaemia in rats. Administration of sodium glutamate intravenously before ischaemia accelerated the shift of water dose-dependently. On the contrary, preischaemic administration of MK-801, an NMDA antagonist, delayed the progression of cytotoxic oedema due to brain ischaemia. We consider that glutamate and NMDA antagonists may have important roles in the development and prevention of cytotoxic oedema in the ischaemic state.