31P nuclear magnetic resonance spectroscopy: noninvasive biochemical analysis of the ischemic extremity

Abstract

The biochemical effects of peripheral vascular disease on skeletal muscle have not been characterized precisely because of the lack of satisfactory noninvasive analytic methods. 31P nuclear magnetic resonance (NMR) spectroscopy was used to measure the high-energy phosphate compounds, phosphocreatine (PCr) and adenosine triphosphate, as well as metabolic byproducts, such as inorganic phosphates (Pi) and phosphate monoesters in calf muscles of 214 limbs with peripheral vascular disease. Intracellular pH was also measured. The NMR index (Pi[PCr + Pi]) was used to quantitate the impairment of oxidative phosphorylation as a result of ischemia. Studies done at rest documented the impairment of oxidative metabolism only in limbs with severe ischemia (ankle-brachial pressure index (API) less than 0.4). Exercise resulted in a significant elevation of the NMR index in all limbs and the rate of return of this value toward normal following exercise was prolonged even in limbs with moderate ischemia (0.4 less than or equal to API less than or equal to 0.9). Correlation of 31P NMR parameters with arteriograms showed that infrapopliteal occlusions resulted in prolonged recovery times only when the superficial femoral artery was occluded and emphasized the metabolic consequences of multisegmental disease. Accumulation of glycolytic pathway intermediates correlated with the decrease in muscle cell pH observed with exercise. Despite immediate improvement in symptoms and hemodynamic parameters following revascularization, return to normal biochemical function occurs over a prolonged period of time. This study demonstrates that 31P NMR spectroscopy can successfully measure noninvasively the important phosphorus-containing compounds involved in the bioenergetics of skeletal muscle in vivo rapidly enough to permit real-time determination during exercise and recovery.