Intracellular acidification and volume increases explain R2 decreases in exercising muscle

Exercise-induced decreases in the 1H transverse relaxation rate (R2) of muscle have been well documented, but the mechanism remains unclear. In this study, the hypothesis was tested that R2 decreases could be explained by pH decreases and apparent intracellular volume (Vi′) increases. 31P and 1H spectroscopy, biexponential R2 analysis, and imaging were performed prior to and following fatiguing exercise in iodoacetate-treated (IAA, to inhibit glycolysis), NaCN-treated (to inhibit oxidative phosphorylation), and untreated frog gastrocnemii. In all exercised muscles, the apparent intracellular R2 (R2i′) and pH decreased, while intracellular osmolytes and Vi′ increased. These effects were larger in NaCN-treated and untreated muscles than in IAA-treated muscles. Multiple regression analysis showed that pH and Vi′ changes explain 70% of the R2i′ variance. Separate experiments in unexercised muscles demonstrated causal relationships between pH and R2i′ and between Vi′ and R2i′. These data indicate that the R2 change of exercise is primarily an intracellular phenomenon caused by the accumulation of the end-products of anaerobic metabolism. In the NaCN-treated and untreated muscles, the R2i′ change increased as field strength increased, suggesting a role for pH-modulated chemical exchange. Magn Reson Med 47:14–23, 2002. © 2002 Wiley-Liss, Inc.