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Effects of Load Induced Metabolic Changes of a Single Muscle on Whole Body Physiology

Kevin Moll¹, Alexander Gussew¹, Maria Nisser², Steffen Derlien², and Jürgen R. Reichenbach¹

¹Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany, ²Institute of Physiotherapy, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany

Synopsis

^31PMR spectroscopy enables a non-invasive evaluation of a metabolic response to a given exercise. A combination of this technique with other methods like ¹H MRS, spirometry and blood lactate diagnostics improves the application field. Therefore, a broad range of metabolic parameters were acquired during an exercise of a single calf muscle to evaluate the effects of local energy demands on global parameters. We observed high adaptations resulting in good correlations between peripheral and locally measured values.

Purpose

Phosphorous and proton magnetic resonance spectroscopy (³¹P/¹H-MRS) in loaded skeletal muscles enables non-invasive quantitation of exercise induced adjustments of energy metabolites, such as phosphocreatine (PCr), inorganic phosphate (Pi), as well as acidification, cytosolic buffering capacity, proton efflux or intermuscular lactate¹. Spirometry and blood lactate diagnostics also provide insight into whole body metabolic adaptations but are only indirectly related to local energy demands in muscles during exercise. Therefore, in this study we applied a combination of MRS, spirometry and blood lactate diagnostics to evaluate the effects of local metabolic demands on global parameters.

Methods

14 healthy male subjects (age: 27 ± 4 years) performed a 3 min plantar flexion with the right foot (0.6 bar pedal resistance, pedal frequency 100 bpm)² within an 3 T MR scanner (Magnetom, PRISMA fit, Siemens, Erlangen, Germany). Spirometric data (VO₂ and VCO₂) were collected by using a commercial available spirometric system (PowerCube, Ganshorn, Medizin Electronic GmbH, Niederlauer, Germany). ³¹P- and ¹H-MR spectra were acquired prior to, during and after the load (Fig. 1). In addition, blood lactate concentrations were quantified from blood samples, which were drawn from the right earlobe at defined time points in rest, during the load as well as during the recovery (Fig. 1). Interleaved series of ¹H- and ³¹P-MR spectra were sampled with a double-tuned (¹H/³¹P) flexible surface coil (RAPID Biomedical, Germany) in the m. gastrocnemius medialis by using a 2D FID-CSI sequence (TR/TE = 290/2.3 ms, 90° sinc rf excitation pulses, matrix: 8×8 voxels, slice thickness: 25 mm, voxel size: 25×25×25 mm³, temporal resolution: 8.4 s) and the ¹H-MEGA-PRESS technique (TR/TE: 2000/140 ms, NEX: 16, editing of lactate CH₂ spins at 4.1 ppm³). Locations of the selected CSI slice and MEGA-PRESS voxel are illustrated in Fig. 2. The MEGA-PRESS sequence was used to reduce contamination of the lactate doublet at 1.3 ppm by lipid resonances. The doublet was quantified by assuming a total creatine concentration of 44 mM¹. All MR spectra were analyzed with the jMRUI 4.0 software (www.jmrui.eu). Spirometric data of VO₂ recovery were fitted by using a bi-exponential fit. Overshoot of CO₂ was determined by integrating the differences between the VO₂ and VCO₂ curves.

Results

In all subjects, the load was associated with strong tissue acidification (end-exercise pH of 6.45 ± 0.19) as well as a PCr depletion below 20% followed by a noticeable slow PCr recovery (τ_PCr = 303 ± 141 s). Two minutes after the end of exercise, lactate concentrations revealed high inter-individual variation (59 ± 23 mM) and were negatively correlated with post-load pH values (R = -0.66, p = 0.01). The increase of inter-muscular lactate concentrations was also reflected in elevated blood lactate concentrations (pre-load: 1.4 ± 0.3 mmol/l; post-load: 3.1 ± 1,5 mmol/l). A significant positive correlation was determined between the post-load muscle and blood lactate concentrations (R = 0.73, p < 0.005). The O₂ consumption and CO₂ exhalation during the load phase attained 0.95 ± 0.31 l/min and 1.0 ± 0.37 l/min, respectively. After the load, a weak positive correlation was observed between the time rates of the PCr and VO₂ recoveries (R = 0.44, p = 0.01). In all subjects, distinct CO₂ overshoots were estimated (3.4 ± 1.3 l/min), which were positively correlated with post-load lactate concentrations in the muscle (R = 0.63, p = 0.016) as well as in the blood (R = 0.66, p = 0.01).

Discussion and Conclusion

In this study, combined spectroscopic, spirometric and blood lactate measurements were applied to describe the local and global physiological adaptations to high intense muscular loads. Despite stressing only a small specific muscle group we were able to measure high respiration and blood lactate changes. Strong correlations between measured lactate concentrations in the periphery and in the muscle demonstrates the feasibility of ¹H-MRS to quantify the load induced accumulation of lactate, which is a crucial exercise limiting parameter. As previously described, we also found a link between the recovery rates of aerobic PCr store refilling and global oxygen demand after the load⁴. Based on the demonstrated advantages of such combined measurements, our future studies will focus on training specific physiological adaptations in order to provide a more differentiated view on training efficiency aspects.

Acknowledgements

This work was supported by the Competence Centre for Interdisciplinary Prevention (KIP) at the Friedrich Schiller University Jena and the German Professional Association for Statutory Accident Insurance and Prevention in the Foodstuffs Industry and the Catering Trade (BGN). K.M. is supported by a graduate scholarship of the Friedrich-Schiller-University Jena (Landesgraduiertenstipendium). K.M. also acknowledges support by the German Academic Exchange Service (DAAD) for a short-term international scholarship at the University of Liverpool (57044996). The authors declare to have no relevant financial interests to disclose with regard to this study.

References

1 Ren J et al. Noninvasive monitoring of lactate dynamics in human forearm muscle after exhaustive exercise by ¹H-magnetic resonance spectroscopy at 7 tesla. Magn Reson Med. 2013; 70(3): 610-9.

2. Tschiesche K et al. MR-compatible pedal ergometer for reproducible exercising of the human calf muscle Med Eng Phys. 2014; 36(7): 933-37.

3. Tschiesche K et al. Multimodal determination of load changes in the muscle - A combination of ¹H-MEGA-PRESS and blood sampling.Proc ISMRM, vol. 23,2015

4. Rossiter HB et al. Inferences from pulmonary O₂ uptake with respect to intramuscular [phosphocreatine] kinetics during moderate exercise in humans J Physiol. 1999; 518(3): 921-32.

Figures

Figure 1: Data acquisition scheme consisting of three different phases (rest, load and recovery). During the whole experiment spirometry data were acquired continuously. Blood samples were taken at specific time points (red arrows). ³¹P MRS and ¹H MRS were acquired interleaved with a short shimming gap during the recovery. Due to movement artifacts viable ¹H MRS measurements were impossible while the subject pushed the pedal.

Figure 2: Typical voxel position in the calf muscle (m. gastrocnemius medialis) for the ³¹P CSI and the ¹H MRS, respectively. A representative ‘stack plot’ of ³¹P-MR spectra (left) as well as a non-edited (black) and difference (red) ¹H-MR spectra (right) is shown below.

Figure 3: Scatter plot of individual blood lactate muscle lactate (a) and pH values (b) together with the linear regression line (dashed line). (c) and (d) show the positive correlation between lactate values measured in the muscle to excess CO₂ as well as in blood lactate together with the linear regression line (dashed line).

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)

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