Simultaneous cardiac mechanics and phosphorus-31 NMR spectroscopy during global myocardial ischemia and reperfusion in the intact dog

To investigate the high-energy phosphate metabolic correlates of left ventricular (LV) dysfunction during the onset and recovery from severe, global myocardial ischemia in vivo, seven preinstrumented closed-chest dogs had ECG-gated phosphorus-31 (31P) NMR-spectroscopy (NMR-S) studies performed and LV micromanometer and sonomicrometer data measured before, during, and every 5 min following severe occlusive global myocardial ischemia. Ischemic LV + dP/dtmax fell from 2396 +/- 576 mm Hg/s at baseline to 2185 +/- 478 mm Hg/s (p less than 0.05) and did not normalize until after 30 min of reperfusion. LV ejection fraction (EF) decreased significantly (0.32 +/- 0.07 EF units to 0.12 +/- 0.13 EF units; p less than 0.05) and did not recover by 30 min of reperfusion (0.27 +/- 0.09 units; P less than 0.05 vs baseline). Simultaneous 31P NMR-S studies demonstrated excellent beta-ATP signal-to-noise (10 +/- 4:1). Myocardial acidosis occurred during global ischemia (delta pH = -0.22 +/- 0.23 units; p less than 0.05), with recovery at 30 min of reperfusion. Inorganic phosphate/phosphocreatine ratio (Pi/PCr) increased significantly during ischemia (0.46 +/- 0.07 to 0.61 +/- 0.07; P less than 0.05), with delayed normalization of this ratio at 30 min of reperfusion. beta-ATP peak area did not change during ischemia. Pi/PCr and LV contractility (+dP/dtmax) were significantly correlated at baseline (r = -0.70) and during global ischemia (r = -0.78; p less than 0.01), but not during recovery (r = 0.006; p = NS). Therefore, the simultaneous evaluation of high-fidelity hemodynamic data and topical 31P NMR-S can be performed in the intact state.     

Exertional heatstroke and muscle metabolism: an in vivo 31P-MRS study.

An impairment of muscle energy metabolism has been suggested as a predisposing factor for, as well as a consequence of exertional heatstroke (EHS). Thirteen young men were investigated 6 months after a well-documented EHS using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined at rest, during a graded standardized exercise protocol (360 active plantar flexions) and during recovery. Also the leg tissue blood flow was determined by venous occlusion plethysmography during the MRS procedure. Sixteen age-matched healthy male volunteers served as control group. In resting muscle, there were no significant differences between the groups as regards pHi, Pi/PCr, and ATP/PCr+Pi+PME ratios. During steady state exercise conditions, effective power outputs were similar for both groups at each level of exercise: 20, 35, and 50% of maximal voluntary contraction (MVC) of the calf muscle. No significant differences were shown between the two groups in Pi/PCr, pHi, or changes of leg blood flow at each level of exercise. At 50% MVC, Pi/PCr was 0.48 +/- 0.08 vs 0.47 +/- 0.05 (P = 0.96), pHi was 6.94 +/- 0.03 vs 6.99 +/- 0.02, respectively (P = 0.13). Finally, the rate of PCr resynthesis during recovery was not significantly different between the two groups: t1/2 PCr = 0.58 +/- 0.07 vs 0.50 +/- 0.05 min, respectively (P = 0.35). Therefore, no evidence of an impairment of muscle energy metabolism was shown in the EHS group during a standardized submaximal exercise using 31P-MRS performed 6 months after an EHS.     

The fate of inorganic phosphate and pH in regional myocardial ischemia and infarction: a noninvasive 31P NMR study

To determine the characteristic appearance of phosphorus (31P) nuclear magnetic resonance spectra in acute and chronic myocardial infarction in situ, cardiac-gated depth-resolved surface coil spectroscopy (DRESS) at 1.5 T was used to monitor 31P NMR spectra from localized volumes in the left anterior canine myocardium for up to 5 days following permanent occlusion of the left anterior descending coronary artery. Coronary occlusion initially produced regional ischemia manifested as significant reductions in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratios and intracellular pH (P less than 0.05, Student's t test) in endocardially displaced spectra acquired in periods as short as 50 to 150 s postocclusion. Spectra acquired subsequently revealed either (i) restoration of near-normal phosphate metabolism sometime between 10 and about 50 min postocclusion or (ii) advancing ischemic phosphate metabolism at about an hour postocclusion, and/or (iii) maintenance of depressed PCr/Pi ratios for up to 5 days postocclusion with a return of the apparent pH to near normal values between 6 and 15 h postocclusion. Postmortem examination of animals exhibiting the first type of behavior revealed the existence of coronary collateral vessels. The last type of behavior indicates that Pi remains substantially localized in damaged myocardium for days following infarction. The location and size of infarctions were determined postmortem by staining excised hearts. The smallest infarctions detected by 31P DRESS weighed 4.9 and 7.5 g. The most acidic pH measured in vivo was 5.9 +/- 0.2. Infarctions aged 1/2 day to 5 days were characterized by elevated but broad Pi resonances at 5.1 +/- 0.2 ppm relative to PCr and significantly depressed PCr/Pi ratios (P less than 0.002, Student's t test) relative to preocclusion values. Contamination of Pi resonances by phosphomonoester (PM) components is a significant problem for preocclusion Pi and pH measurements. These results should be applicable to the detection and identification of human myocardial infarction using 31P NMR and DRESS.     

31P NMR characterization of graded traumatic brain injury in rats

Irreversible tissue injury following central nervous system trauma is believed to result from both mechanical disruption at the time of primary insult, and more delayed "autodestructive" processes. These delayed events are associated with various biochemical changes, including alterations in phosphate energy metabolism and intracellular pH. Using 31P NMR, we have monitored the changes in phosphorus energy metabolism and intracellular pH in a single hemisphere of the rat brain over an 8-h period following graded, traumatic, fluid percussion-induced brain injury. Following trauma the ratio of phosphocreatine to inorganic phosphate (PCr/Pi) declined in each injury group. This decline was transitory with low injury (1.0 +/- 0.5 atm), biphasic with moderate (2.1 +/- 0.4 atm) and high (3.9 +/- 0.9 atm) injury, and sustained following severe injury (5.9 +/- 0.7 atm). The initial PCr/Pi decline in the moderate and high injury groups was associated with intracellular acidosis; however, the second decline occurred in the absence of any pH changes. Alterations in ATP occurred only in severely injured animals and such changes were associated with marked acidosis and 100% mortality rate. After 4h, the posttraumatic PCr/Pi ratio correlated linearly with the severity of injury. We suggest that a reduced posttraumatic PCr/Pi ratio may be indicative of altered mitochondrial energy production and may predict a reduced capacity of the cell to recover from traumatic injury.     

Acute volume loading studied in cat myocardium with 31P nuclear magnetic resonance

To study the effects of acute volume loading on myocardial metabolic and mechanical function, seven cats were volume loaded via anastomosis of the abdominal aorta to the vena cava (AV shunt). Metabolic effects were evaluated with 31P nuclear magnetic resonance (NMR). Mechanical function was evaluated with heart rate X systolic blood pressure product (HR X SBP). Shunts were opened for 1-2 h during which time phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi), and HR X SBP were monitored. High-energy phosphate energetics as determined by Pi/PCr and PCr/ATP ratios were correlated with HR X SBP. Opening of the AV shunts was associated with an increase (four cats) or a decrease (three cats) in HR X SBP. Pi/PCr ratios increased and PCr/ATP ratios decreased in cats with an increase in HR X SBP. In cats with a decrease in HR X SBP, Pi/PCr and PCr/ATP generally did not change significantly. In summary, acute volume loading could be associated with an increase or decrease in myocardial external work as evaluated by HR X SBP, accompanied by metabolic changes suggestive of appropriate induction of state 3 metabolism (active metabolic state: ADP + Pi----ATP) in those cats with increased mechanical work, and minimal change in bioenergetics in cats with no or minimal increase in mechanical work. These induced metabolic responses to myocardial mechanical loading can be evaluated with 31P NMR techniques and may provide insight into in vivo metabolic control mechanisms.     

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.     

Early stage detection of chemotherapeutic effect on 203 GL glioma in mice as studied by P-31 NMR and flow cytometry

The effect of chemotherapy against glioma in mouse was evaluated by 31P NMR spectroscopy and flow cytometry. We found that administration of ACNU or tegafur at a dose less than LD50 resulted in the partial suppression of the ratio of inorganic phosphate (Pi)/phosphocreatine (PCr) and phosphomonoester (PME)/creatine phosphate (PCr) after 24 or 48 hr, although these ratios are usually increased together with growth of tumors. Flow cytometric analysis of glioma in vivo showed an accumulation in cells containing tetraploid DNA by G2M block 24-48 hr after treatment. However, the change occurred at a period slightly later than that of the Pi/PCr ratio. In contrast, histological change was noted at eight days after administration. Hence, it is concluded that in vivo 31P NMR spectroscopy can detect a change in metabolic pathways in tumors as early as 24-48 hr after the administration of chemotherapeutic agents.     

Peak oxygen consumption and skeletal muscle bioenergetics in African-American and Caucasian men

OBJECTIVE: To compare peak oxygen consumption (VO2peak) and skeletal muscle oxidative metabolism between nine African-American and nine Caucasian men. METHODS: Subjects performed arm ergometry to exhaustion. On a separate occasion 31phosphorous-nuclear magnetic resonance spectroscopy (31P-NMRS) was used to determine the concentrations of phosphorous (Pi), phosphocreatine (PCr), and the intracellular pH of the flexor carpi radialis before and during 4 min of steady-state, wrist flexion exercise performed at 28% (15 W) of each subject's peak voluntary contraction. RESULTS: The Pi/PCr ratio was used as an indirect measure of skeletal muscle oxidative metabolism. VO2peak was lower in the African-Americans compared with the Caucasians (means +/- SD, 19.4 +/- 3.4 vs 23.3 +/- 4.0 mL x kg(-1) x min(-1)) (P < 0.05). No significant between group difference was noted in the Pi/PCr ratio at rest (0.10 +/- 0.02 both groups). However, resting pH was lower in the African-Americans (6.99 +/- 0.04 vs 7.03 +/- 0.05) (P < 0.05). Exercise caused an increase in the Pi/PCr ratio in the African-Americans (1.06 +/- 0.11), which was higher than the increase observed in the Caucasians (0.50 +/- 0.14) (P < 0.05). pH levels decreased to a lower level during exercise in the African-Americans (6.89 +/- 0.04) than in the Caucasians (6.98 +/- 0.05) (P < 0.05). CONCLUSIONS: This select group of African-American men achieved a lower VO2peak than the Caucasian men. Variations in skeletal muscle oxidative metabolic components may explain this difference.     

Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. III. Alterations of muscle blood flow and metabolism during sepsis.

In the conclusion of this series of reports, the application of 31P/2H NMR to investigate the pathophysiology of sepsis in rat hindlimb muscle is demonstrated. Sepsis decreased muscle [PCr] by 18%, 18 +/- 4 SD vs 22 +/- 4 SD mmol/kg tissue wet wt (P = 0.01) in control rats but [ATP] was unchanged, 6 mmol/kg tissue wet wt (P = 0.2). The derived free cytosolic [ADP] in the two groups was similar, [ADP]septic = 0.023 +/- 0.004 SD and [ADP]control = 0.021 +/- 0.003 SD mmol/kg tissue wet wt, and not statistically different (P = 0.14). Likewise [Pi] in the septic and control groups was not statistically different, [Pi]septic = 1.1 +/- 0.5 SD and [Pi]control = 1.2 +/- 0.4 SD mmol/kg tissue wet wt (P = 0.2). Septic rats presented the symptom of respiratory alkalosis evidenced by elevated blood pH. Sepsis decreased muscle blood flow by 33%, P = 0.003, but examination of individual subjects did not demonstrate a correlation with the reduction in [PCr]. Thus, a metabolic energy deficit caused by cellular ischemia/hypoxia is not a likely cause of cellular abnormality in rat hindlimb muscle during sepsis.     

Preservation of high-energy phosphate reserves in a cat model of post-ischemic myocardial dysfunction.

Brief episodes of myocardial ischemia are known to cause reversible depression of regional myocardial contraction after reperfusion. One of the mechanisms of this persistent regional dysfunction has been proposed to be depletion of high-energy phosphate compounds. Eight cats were prepared with a reversible snare occluder around the left anterior descending artery (LAD); a surface coil sutured to the epicardial surface over the LAD territory for measurement of 31-phosphorus (31P) magnetic resonance spectroscopy (MRS) spectra; and a pair of ultrasonic crystals implanted in the mid-myocardium for measurement of regional segment length shortening. The baseline value of percent segment length shortening (%SS) was 12.8 +/- 1.4%. Increased afterload did not significantly alter high-energy phosphate levels or %SS. All animals exhibited passive systolic bulging during occlusion (-8.4 +/- 3.6% systolic shortening) as well as reduced phosphocreatine (PRc, 30 +/- 3% of control) and increased inorganic phosphorus (Pi) (239 +/- 18%), but there was no change in adenosine triphosphate (ATP). During reflow, %SS did not completely recover (4.0 +/- 2.9%, P less than .05 versus baseline). PCr and Pi returned to control levels during the first 30 minutes of reperfusion. Increased afterload had no significant effect on high-energy phosphates or %SS in stunned hearts. These findings indicate a lack of correlation between recovery of high-energy phosphate stores and regional myocardial contractility in stunned myocardium. High-energy phosphate reserves are preserved in stunned myocardium and are unlikely to be a direct cause of myocardial dysfunction.     

Recovery kinetics throughout successive bouts of various exercises in elite cyclists

PURPOSE: In the present study we investigated whether a high volume of cycling training would influence the metabolic changes associated with a succession of three exhaustive cycling exercises. METHODS: Seven professional road cyclists (VO2max: 74.3 +/- 3.7 mL.min.kg; maximal power tolerated: 475 +/- 18 W; training: 22 +/- 3 h.wk) and seven sport sciences students (VO2max: 54.2 +/- 5.3 mL.min.kg; maximal power tolerated: 341 +/- 26 W; training: 6 +/- 2 h.wk) performed three different exhaustive cycling exercise bouts (progressive, constant load, and sprint) on an electrically braked cycloergometer positioned near the magnetic resonance scanner. Less than 45 s after the completion of each exercise bout, recovery kinetics of high-energy phosphorylated compounds and pH were measured using P-MR spectroscopy. RESULTS: Resting values for phosphomonoesters (PME) and phosphodiesters (PDE) were significantly elevated in the cyclist group (PME/ATP: 0.82 +/- 0.11 vs 0.58 +/- 0.19; PDE/ATP: 0.27 +/- 0.03 vs 0.21 +/- 0.05). Phosphocreatine (PCr) consumption and inorganic phosphate (Pi) accumulation measured at end of exercise bouts 1 (PCr: 6.5 +/- 3.2 vs 10.4 +/- 1.6 mM; Pi: 1.6 +/- 0.7 vs 6.8 +/- 3.4 mM) and 3 (PCr: 5.6 +/- 2.4 vs 9.3 +/- 3.9 mM; Pi: 1.5 +/- 0.5 vs 7.7 +/- 3.3 mM) were reduced in cyclists compared with controls. During the recovery period after each exercise bout, the pH-recovery rate was larger in professional road cyclists, whereas the PCr-recovery kinetics were significantly faster for cyclists only for bout 3. DISCUSSION: Whereas the PDE and PME elevation at rest in professional cyclists may indicate fiber-type changes and an imbalance between glycogenolytic and glycolytic activity, the lower PCr consumption during exercise and the faster pH-recovery kinetic clearly suggest an improved mitochondrial function.     

Muscle high-energy metabolites and metabolic capacity in patients with heart failure

OKITA, K., K. YONEZAWA, H. NISHIJIMA, A. HANADA, T. NAGAI, T. MURAKAMI, and A. KITABATAKE. Muscle high-energy metabolites and metabolic capacity in patients with heart failure. Med Sci. Sports. Exerc., Vol. 33, No. 3, 2001, pp. 442-448. Background: Various abnormalities in skeletal muscle have been demonstrated by biopsy in patients with chronic heart failure (CHF). In mammalian muscles, high-energy metabolite composition at rest (HEMC) provides data on important metabolic characteristics; however, the significance of HEMC has not been clarified in patients with CHF. Therefore, we investigated HEMC in normal subjects and patients with CHF and examined its relation to muscle metabolic capacity and exercise tolerance. Methods: High-energy metabolites (phosphocreatine (PCr), inorganic phosphate (Pi), and ATP) in resting calf muscle were measured by 31P-magnetic resonance spectroscopy (31P-MRS), and ratios of Pi to PCr, Pi to ATP, and PCr to ATP were calculated in 34 patients with CHF and 13 age- and size-matched normal subjects. Muscle metabolism was evaluated during local exercise of unilateral plantar flexion by 31P-MRS. Metabolic capacity was estimated by the rate of PCr breakdown in relation to the workload. Systemic exercise capacity was evaluated by a bicycle ergometer. Results: The ratio of PCr to ATP was significantly increased in patients with CHF compared with controls (3.06 +/- 0.43 vs 2.72 +/- 0.36, P < 0.05) and was significantly correlated with metabolic capacity (r = -0.37, P < 0.01) and with peak oxygen uptake (r = -0.45, P < 0.01). There was a significant correlation between metabolic capacity and peak oxygen uptake (r = 0.53, P < 0.001). Conclusion: HEMC was altered in patients with CHF, and this change was related to metabolic capacity and exercise capacity. These findings provide new insight into the mechanism of impaired muscle metabolism in CHF.     

Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy

The high-energy myocardial phosphate metabolism of four patients with acute anterior myocardial infarction after coronary angioplasty and drug therapy was evaluated with cardiac-gated phosphorus magnetic resonance (MR) depth-resolved surface coil spectroscopy (DRESS) 5-9 days after the onset of symptoms. Significant reductions (about threefold) in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratio and elevations in the Pi to adenosine triphosphate (ATP) ratio were observed in endocardially or transmurally derived MR spectra when compared with values from epicardially displaced spectra and values from seven healthy volunteers (P less than .05). High-energy phosphate metabolites and Pi ratios did not vary significantly during the cardiac cycle in healthy volunteers. However, contamination of Pi resonances by phosphomonoester components, including blood 2,3-diphosphoglycerate, precluded accurate spectral quantification of Pi and pH. The results indicate that localized P-31 MR spectroscopy may be used to directly assess cellular energy reserve in clinical myocardial infarction and to evaluate metabolic response to interventions.     

Noninvasive measurement of muscle high-energy phosphates and glycogen concentrations in elite soccer players by 31P- and 13C-MRS

PURPOSE: The purpose of this study was to measure noninvasively the absolute concentrations of muscle adenosine triphosphate [ATP], phosphocreatine [PCr], inorganic phosphate (Pi), and glycogen [Gly] of elite soccer players. METHODS: Magnetic resonance spectroscopy (31P- and 13C-MRS) was used to measure the concentrations of metabolites in the calf muscles of 18 young male players [age = 17.5 +/- 1.0 (SD) yr]. RESULTS: Average muscle [PCr] and [ATP] were 17.8 +/- 3.3 and 6.0 +/- 1.2 mmol x (kg wet weight)(-1), respectively. The ratios of Pi/PCr and PCr/ATP were 0.15 +/- 0.05 and 3.00 +/- 0.26, respectively. The muscle [Gly] was 144 +/- 54 mmol x (kg wet weight)(-1). There was a high correlation (r = 0.93, P < 0.0001) between muscle ATP and PCr concentrations, but there was no correlation between [Gly] and [PCr] or [ATP]. The concentrations of the different metabolites determined in the present study with noninvasive MRS methods were within the ranges of values reported in human muscle from biochemical analysis of muscle biopsies. CONCLUSION: MRS methods can be utilized to assess noninvasively the muscle energetic status of elite soccer players during a soccer season. The high correlation between ATP and PCr might be indicative of fiber type differences in the content of these two metabolites.     

Effect of repetitive brief episodes of cardiac ischemia on 31P magnetic resonance spectroscopy in the cat

Angina is characterized by brief periods of ischemia followed by reperfusion; the cumulative effect of these episodes on energetics of the myocardium has not been fully elucidated. This study used an in vivo feline model for the assessment of high-energy phosphate compounds during brief sequential periods of ischemia and reperfusion. Nine adult, open-chest, anesthetized cats were prepared with a reversible occluder around the proximal left anterior descending artery and a 1.2-cm-inside diameter coil sutured on the myocardial surface in the distribution of the left anterior descending coronary artery. Levels of PCr, Pi, and ATP (beta-phosphate signal) were measured by 31P MRS in a GE CSI 2-T NMR spectrometer/imager. Measurements were obtained during a control period and during three successive occlusion-deocclusion periods of roughly 12 and 20 min' duration, respectively. The last deocclusion period was observed for 60 min. Electron microscopy was performed in two animals. PCr declined (P less than 0.01) rapidly following each occlusion to 51 +/- 5.2% (occlusion 1), 53 +/- 5.8% (occlusion 2), and 48 +/- 5.7% (occlusion 3) of the control value by 6 min. Pi rose (P less than 0.01) with the three sequential occlusions to 253 +/- 46, 288 +/- 57, and 277 +/- 46%, respectively. PCr and Pi returned to baseline promptly with reperfusion, while ATP showed a gradual decline throughout the experiment, decreasing to 77 +/- 7.2% of control at the end of the last reperfusion (P less than 0.05). Although PCr returned to baseline during reperfusion, ATP did not, suggesting a reduction in the nucleotide pool. These findings indicate that the repeated episodes of ischemia, which are insufficient to produce necrosis, can have an effect on myocardial high-energy phosphate metabolism as evidenced by mild depletion of ATP.     

Human breast cancer in vivo: H-1 and P-31 MR spectroscopy at 1.5 T

To assess the potential of in vivo magnetic resonance (MR) spectroscopy for breast cancer, hydrogen-1 and phosphorus-31 MR spectra of five malignant human breast tumors were compared with those of unaffected breast tissue. The water-to-fat ratio was high in the tumors (average, 2.2) but low in the unaffected tissue (average, 0.3). The P-31 spectrum of normal breast tissue showed low levels of phosphomonoesters (PMEs), inorganic phosphate, phosphodiesters (PDEs), and ATP. In addition, an intense phosphocreatine (PCr) signal was observed in breast tissue of young women: The relative intensities of the PCr and ATP signals had a mean value of 1.9. The tumor spectrum showed elevated levels of PMEs, Pi, and PDEs, while no PCr was seen (PCr/ATP less than 0.2). In two breast cancers treated with radiation therapy, resulting in a decrease of tumor volume of more than 50%, a similar change in the tumor P-31 spectrum was observed: An intense PCr signal developed (PCr/ATP = 1.1). Control experiments indicated that the appearance of PCr after radiation therapy was the result of a radiation-induced metabolic change in the tumor itself.     

Characterization of high-energy phosphate compounds during reperfusion of the irreversibly injured myocardium using 31P MRS

Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to monitor regional changes in high-energy phosphorus compounds and intracellular pH during 60 min of acute regional ischemia (acute occlusion of left anterior descending artery) and reperfusion in open-chest cats using a 1.2-cm two-turn coil sutured to the myocardium. During the 60-min ischemic phase, phosphocreatine (PCr) intensity was reduced to 47 +/- 4.9% (mean +/- SE) of control (p less than 0.01) by 15 min postocclusion while adenosine triphosphate (ATP) intensity decreased more slowly with the decrease (66 +/- 5.6%) achieving significance (p less than 0.05) only at 60 min postocclusion. Inorganic phosphate (Pi) increased to a maximum of 397 +/- 42% of control (p less than 0.01) while the pH decreased progressively from 7.36 +/- 0.02 to 6.02 +/- 0.14 (p less than 0.01). After release of occlusion PCr intensity recovered to 86 +/- 12% of the initial control value at 15 min postreperfusion but showed a subsequent downward trend to 79 +/- 8.8%. The ATP did not recover but tended to decline further during reperfusion. The Pi intensity decreased to 260 +/- 38% of control while the pH increased to 7.01 +/- 0.23 by 15 min postreperfusion. Thus, the reperfused irreversibly injured myocardium is characterized by persistent depletion of PCr and ATP and elevation of Pi. Phosphorus-31 MRS provides a nondestructive method for characterizing the reperfused irreversibly damaged myocardium.     

The use of nuclear magnetic resonance to evaluate muscle injury.

Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are new and powerful tools to study tissue biochemistry, and to provide precise anatomical visualization of soft tissue structures. This review focuses on the use of these techniques to study exercise-induced muscle injury. MRS measurements show an increase in the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) 1-7 d after eccentric exercise. This increase in Pi/PCr could be due to either increases in extracellular Pi or small increases in resting muscle metabolism. Increased Pi/PCr is also seen during training programs and may indicate persistent muscle injury. Increased resting Pi/PCr with injury was not associated with altered metabolism during exercise. Elevations in resting Pi/PCr have been used to show increased susceptibility of dystrophic muscle to exercise-induced injury. Progressive clinical deterioration in dystrophic dogs is marked by impaired muscle metabolism, and the presence of low oxidative muscle fibers not seen in normal dogs. MRI shows increased proton T2 relaxation times following eccentric exercise that last up to 80 d after injury, and can reflect muscle edema as well as longer lasting changes in the characteristics of cell water. MRI demonstrate precise localization of the injured area, with large differences in both location and degree of injury in different subjects following the same exercise protocol. Thus, MRS can provide information on the metabolic response to injury, while MRI provides information regarding the site and extent of the injury. These tools have promise in helping to understand exercise-induced muscle injury.     

Comparison of the clinical state and its changes in patients with Duchenne and Becker muscular dystrophy with results of in vivo 31P magnetic resonance spectroscopy

A total of 14 boys with the Duchenne and Becker forms of muscular dystrophy (DMD, BMD) were examined using ³¹P magnetic resonance (MR) spectroscopy; 12 boys were examined repeatedly. The results were correlated with clinical findings (including those of genetic tests) and with data obtained from examinations of an age-matched control group. Evaluation of results using principal component analysis revealed maximum variability in the following ratios: phosphocreatine/inorganic phosphate (PCr/Pi), phosphocreatine/phosphodiesters (PCr/PDe) and phosphocreatine/phosphomonoesters (PCr/PMe). A decrease in PCr/Pi correlates with weakness of the hip girdle and of the lower part of the shoulder girdle in DMD/BMD patients. The values of all ratios in the group of patients with the DMD phenotype differ significantly from results obtained in the group with the BMD phenotype. Continoous follow-up of patients using ³¹P MR spectroscopy revealed a marked decrease in PCr/Pi in DMD/BMD patients at an age that could be expected in subjects with a typical clinical course of DMD/BMD. An attempt to manage a concomitant disease with prednisone and carnitene was followed by an increase in PCr/Pi in 3 cases. A rise in the PCr/Pi ratio signalled clinical improvement in the patients. A decrease in PCr/Pi was found after controlled physical training, a finding consistent with data obtained from clinical observations describing an adverse effect of physical stress on the dystrophic process. Correspondence to: M. Hájek     

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.