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

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 (k(mono)), myocardial efficiency (double product (DP)/k(mono)), and myocardial blood flow (MBF) were determined before and after L-Arg administration. Baseline k(mono) showed a lower value in the M-group than in the C-group (0.051±0.013 vs 0.070±0.019min(-1), P=0.055). On the other hand, baseline DP/k(mono) was significantly greater in the M-group (1.69±5.9 vs 0.95±1.2×10(5), P=0.004). After L-Arg administration, 4 patients showed significant elevation of k(mono). No relationship was observed between the distribution of k(mono) 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.