Abnormal myocardial energy-production state in mitochondrial cardiomyopathy and acute response to L-arginine infusion - C-11 acetate kinetics revealed by positron emission tomography

Abstract

Background: Cardiomyopathy is a life-threatening condition in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (known as MELAS). However, no effective therapy has been available until now. In the present study cardiac energetics and acute effects of L-arginine (Arg) were evaluated in MELAS patients. Methods and Results: The 6 patients with MELAS (M-group) and 6 volunteers (C-group) underwent dynamic C-11 acetate positron emission tomography (PET) imaging. TCA-cycle metabolic rate (kmono), myocardial efficiency (double product (DP)/kmono), and myocardial blood flow (MBF) were determined before and after L-Arg administration. Baseline kmono showed a lower value in the M-group than in the C-group (0.051±0.013 vs 0.070±0.019 min-1, P=0.055). On the other hand, baseline DP/kmono was significantly greater in the M-group (1.69±5.9 vs 0.95±1.2×105, P=0.004). After L-Arg administration, 4 patients showed significant elevation of kmono. No relationship was observed between the distribution of kmono elevation and the increase in MBF. Conclusions: The TCA cycle metabolic rate is markedly suppressed in MELAS patients, indicating a shift in energy production to the anaerobic pathway, leading to a paradoxical increase in myocardial efficiency. L-Arg can enhance TCA-cycle metabolism, regardless of its vasodilatation effect, and can be used as a treatment for patients with mitochondrial cardiomyopathy.