Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle

Abstract

Using nuclear magnetic resonance (NMR), we have examined the relationship of high-energy phosphate metabolism and perfusion in human soleus and gastrocnemius muscles. With 31P-NMR spectroscopy, we monitored phosphocreatine (PCr) decay and recovery in eight normal volunteers and four heart failure patients performing ischemic plantar flexion. By using echo-planar imaging, perfusion was independently measured by a local [inversion-recovery (T1-flow)] and a regional technique (NMR-plethysmography). After correction for its pH dependence, PCr recovery time constant is 27.5 +/- 8.0 s in normal volunteers, with mean flow 118 +/- 75 (soleus and gastrocnemius T1-flow) and 30.2 +/- 9.7 ml.100 ml-1.min-1 (NMR-plethysmography-flow). We demonstrate a positive correlation between PCr time constant and local perfusion given by y = 50 - 0.15x (r2 = 0.68, P = 0.01) for the 8 normal subjects, and y = 64 - 0.24x (r2 = 0.83, P = 0.0001) for the 12 subjects recruited in the study. Regional perfusion techniques also show a significant but weaker correlation. Using this totally noninvasive method, we conclude that aerobic ATP resynthesis is related to the magnitude of perfusion, i.e., O2 availability, and demonstrate that magnetic resonance imaging and magnetic resonance spectroscopy together can accurately assess muscle functional status.

Adenovirus-Mediated VEGF 121 Gene Transfer Stimulates Angiogenesis in Normoperfused Skeletal Muscle and Preserves Tissue Perfusion After Induction of Ischemia

“…31 P NMR spectroscopy is an established method for the noninvasive assessment of metabolic correlates of tissue perfusion. [22][23][24] In the present study, muscle metabolism in the gastrocnemius muscle, distal to the site of induced ischemia, was assessed. Our results demonstrated markedly improved bioenergetic capacity of the ischemic gastrocnemius muscle in AdCMV.VEGF 121 -treated animals compared with controls.…”

How to investigate oxygen supply, uptake, and utilization simultaneously by interleaved NMR imaging and spectroscopy of the skeletal muscle

“…Remembering that most of the O 2 in the cell is bound to Mb, the time-changes in muscle oxygen content can be obtained from the Mb de-or re-oxygenation rates measured by 1 H NMR:…”

“…This drawback is well illustrated in one study aimed at elucidating the relationship between skeletal muscle perfusion and oxidative phosphorylation (1). Due to technical constraints, post-ischemic reactive hyperemia and creatine rephosphorylation rate were measured during separate experimental sessions.…”

“…Concurrent heteronuclear NMR was pioneered both in Oxford and in Philadelphia (4,5) and culminated with the demonstration of simultaneous in vivo 1 H, 19 F, 31 P, and 23 Na NMR acquisitions (6). The relationship between intracellular sodium accumulation and high-energy phosphate depletion was demonstrated during rat leg ischemia by 23 Na/ 31 P spectroscopy (7).…”

Time‐courses of perfusion and phosphocreatine in rat leg during low‐level exercise and recovery

“…Neither of those studies included measurements of PCr. Combined MR measurements of perfusion and PCr changes were first performed by Toussaint et al (27). They acquired perfusion measurements at rest and at a single time-point immediately following ischemic exercise and measured PCr recovery during the hyperemic period following exercise.…”