CHARACTERIZATION OF MUSCLE METABOLIC DYSFUNCTION IN CYSTIC FIBROSIS USING 31P-MRS

Objectives: The objective of this research-in-progress is to identify and characterize the underlying defect (s) in muscle metabolism in individuals with cystic fibrosis (CF) using 31phosphorus magnetic resonance spectroscopy (31P-MRS). Previous work has demonstrated a decrease in peak anaerobic power in female athletes with CF despite normal lung function and good nutritional status (Selvadurai et al 2003; Am J Respir Crit Care Med 168:1476).

Methods: We are recruiting and testing 80 participants (40 females, 40 males). Half of the subjects are individuals with cystic fibrosis who are being matched with healthy controls for gender, age, and activity level (HAES). Using specific ergometric protocols to assess aerobic and anareobic performance, we are applying non-invasive 31P-MRS technology to quantify abnormalities in aerobic and/or anaerobic metabolism and their relative impact on muscle energy production and substrate recovery. Aerobic and anaerobic metabolic parameters are being derived from graphical analysis. We are correlating these abnormalities with the metabolic profile and motor performance obtained from the forearm ischemic lactate test and from standardized cycle ergometry (maximal incremen tal and isokinetic cycling).

Results: Data collection is underway and parameter estimates are being collected for inorganic phosphorus, phosphocreatine, and adenosine triphosphate peaks, as well as pH, Mg2+, and ATP-ase activity during rest, aerobic exercise, anaerobic exercise, and recovery for individuals with cystic fibrosis and healthy controls, for both male and female participants. Results will be analyzed using a 2-way ANOVA (factors: gender, group). Our preliminary results suggest important differences between healthy controls and CF patients in resting phosphocreatine levels, which are reduced in CF, and in end-exercise pH, which is less acidotic in CF patients. Conclusion: Elucidation of the mechanism (s) by which CF adversely affects muscle metabolism, will increase our understanding of the fundamental nature of the muscle dysfunction in CF and facilitate the development of energy-system specific ergometric treatment protocols. Furthermore, this 31P-MRS technique may provide a useful prognostic tool and a means to assess the efficacy of therapeutic interventions in CF.