Simultaneous 31P MRS of the soleus and gastrocnemius in Sherpas during graded calf muscle exercise

Abstract

The observation that the amount of lactate formed during hypobaric hypoxia decreases with the severity of hypoxia has become known as the "lactate paradox." We used noninvasive 31P magnetic resonance spectroscopy (MRS) to further probe this problem and explore the nature of muscle metabolism during rest-exercise-recovery transitions in Sherpas indigenous to the high Himalayas of Nepal. MRS data were obtained using a whole body 1-m bore, 1.5-T Phillips Gyroscan spectrometer. Muscle-specific localization of MRS data acquisition was achieved by means of a modified image-selected in vivo spectroscopy sequence (ISIS). The spectra acquired from the medial and lateral gastrocnemius muscle, rich in fast-twitch fibers, were well constrained by selective excitation and by the boundary of the leg. The spectra from a third region contained signals predominantly from the soleus, a muscle formed mainly of slow-twitch fibers. We quantified relative concentration changes in phosphocreatine (PCr), Pi, and ATP during a series of calf muscle work bouts; free ADP concentrations were calculated on the assumption that the creatine phosphokinase reaction was always essentially at equilibrium. Hydrogen ion concentrations were calculated from the chemical shift of Pi, which represents the equilibrium between mono- and diprotonated phosphate. Plantar flexion was quantified using a calf muscle ergometer designed for operation within a 1-m whole body magnet. We found that the concentration of ATP was rigorously regulated and thus did not change despite large changes in ATP turnover rates required through exercise. The relative concentrations of PCr and Pi were linear functions of the percent maximum work rate of the lateral and medial gastrocnemius, but on transition to exercise the fractional concentration changes in these metabolites were much less than the fractional change in muscle ATP turnover rates. The relationship between muscle ATP turnover rate and free ADP concentration was complex; again, a kinetic order of 1 was not observed. In contrast to the gastrocnemius, the soleus muscle sustained much smaller changes in the concentrations of these crucial metabolites during rest-work-recovery transitions. Unlike the situation in most other muscles rich in fast-twitch fibers characterized by lactate-associated acidosis during muscle work, the intracellular pH in gastrocnemius of Sherpas was stable through these protocols, which is consistent with the low lactate production (i.e., with the lactate paradox) observed in indigenous highlanders.

Skeletal muscle energetics assessed by 31P-NMR in prepubertal girls with a familial predisposition to obesity

“…Others have observed a similar finding in exercise of different intensities. 32 With submaximal steady-state exercise protocols, the rates of ATP synthesis and hydrolysis for muscle contraction are matched, resulting in a constant ATP level in the muscle. 33 This type of exercise protocol offers the advantage of better compliance, a greater specificity to oxidative ATP synthesis, and less influence of fatigue mechanisms, as seen with ischemic protocols.…”

“…A unique system of separating the effects of the two muscles demonstrated that the soleus sustains much smaller changes in the concentrations of P i and PCr during rest -exerciserecovery protocols. 32 These authors hypothesized that the different responses of the two muscle types to the exercise protocols may have been due to the different oxidation of fuels; the fast-twitch fibers of the gastrocnemius preferentially burn carbohydrate and the slow-twitch fibers of the soleus preferentially oxidize fat during exercise. 32 We have previously shown that 24 h substrate oxidation, measured by whole room respiration calorimetry, is similar among these same girls with and without a familial predisposition to obesity.…”

PETER HOCHACHKA: Adventures in Biochemical Adaptation

“…Because fatty acid oxidation results in O 2 wasting, i.e., more O 2 is used per unit cardiac work performed compared with glucose oxidation, the greater reliance upon glucose as a premium fuel suggests greater efficiency in both energy production and in O 2 use in the hearts of Quechua compared with those of lowlanders. In Sherpas breathing normoxic or hypoxic air, MRS of calf muscles showed tight coupling between ATP synthesis and hydrolysis rates, despite large changes in work rate (50). The greater reliance on aerobic pathways for energy production and the efficiency of coupling between energy production and energy use under hypoxic conditions was proposed to explain partly why lactate and H + do not accumulate to the same extent as in the muscles of lowlanders subjected to these conditions.…”

Plasticity of the Muscle Proteome to Exercise at Altitude

“…This observation and the later finding on elevated mitochondrial volume densities in slow and fast muscle fibers in patients with unilateral intermittent claudication shaped the belief that hypoxia alone is the stimulus for aerobic metabolism (Angquist and Sjostrom, 1980;Terrados et al, 1990). This view was questioned by a series of studies pointing out that residency at altitude shifts muscle to a more glycolytic type, with tighter coupling of energetic processes and ''elevated buffer capacity,'' which reduces lactate efflux during muscle work, the lactate paradox (Brooks et al, 1991;Reeves et al, 1992;Desplanches et al, 1996;Kayser et al, 1996;Allen et al, 1997;Clanton and Klawitter, 2001) These alterations in high altitude natives are accompanied by atrophy in muscle fibers. It is understood that this shrinkage of muscle fibers optimizes capillary diffusion distances in the altitudeacclimatized muscle phenotype (Howald and Hoppeler, 2003).…”