The efficiency of muscle adaptation to training has been shown to be associated with polymorphic variants of the gene for angiotensin converting enzyme (ACE). In particular the insertion/deletion (I/D) polymorphism is associated with muscle performance in exercise and training (3, 4). Persons with I alleles, which is associated with lower ACE activity (5), show better results after aerobic training and higher muscle performance especially in tasks entailing resistance. The I/D ACE polymorphism was also associated with severity in a large group of MCA patients (6), and ACE activity modulation is easily achieved Inhibitors,research,lifescience,medical by drugs with excellent record of efficacy
and tolerability. ACE activity modulation thus appears as a suitable target for chronic therapeutic intervention. The use of the ACE Inhibitors,research,lifescience,medical inhibitor Ramipril may mimic the condition associated with I alleles, and may improve functioning in MCA patients. Materials and methods 8 subjects with biochemically and molecularly proven MCA were recruited. Inclusion criteria were age 18-60, selleck inhibitor absence of major additional medical condition (hypertension, diabetes, cardiopathy, kidney or lung diseases), absence
of pregnancy and presence of adequate Inhibitors,research,lifescience,medical birth control procedures during the duration of the study, absence of other chronic therapy, adhesion to the study. The study was double-blinded and placebo controlled. The subjects AZD-2281 sustained a cycle ergometer exercise test during which maximal workload, maximal heart rate, maximal oxygen uptake (VO2max) were recorded, and were randomly allocated to placebo or active treatment (2.5 mg Ramipril daily). After 12 weeks of treatment the patients repeated the exercise Inhibitors,research,lifescience,medical test. All subjects observed a one month wash-out period, and were then crossed to the opposite treatment. After 12 more weeks of treatment, all patients completed another exercise test. After each period of treatment the patients also completed
the WHO-DAS II: a questionnaire meant to quantify the disability associated with their health condition (7). Exercise test was an incremental Inhibitors,research,lifescience,medical cycloergometer (Seca Cardiotest, Hamburg, Germany) effort conducted until exhaustion. HR, Ventilation, VO2, VCO2 were continuously recorded with a portable Carfilzomib telemetric system (Cosmed K4, Rome, Italy). The t test for paired samples was used to assess inter-treatment changes in parametric variables, and the Wilcoxon test for repeated measures for changes in non-parametric variables. Significance was set at p < 0.05. Results All patients completed the protocol, the treatment was well tolerated and no undesired effect was recorded. All patients exhibited the typical reduction, compared to expected values, of maximal workload and VO2max, with much higher HR/WL ratio. There were no differences in any of the parameters recorded during the exercise testing after any of the treatments (Fig. (Fig.1).1).