MELAS patients demonstrated significantly greater baseline myocardial efficiency compared to healthy controls (1.69 vs 0.95 x 10^5, P=0.004), with L-arginine infusion enhancing TCA-cycle metabolism in 4 of 6 patients.
Observational (n=12)
No
Does L-arginine infusion improve myocardial energy production in patients with mitochondrial cardiomyopathy (MELAS)?
L-arginine infusion acutely enhances TCA-cycle metabolism in patients with MELAS, suggesting a potential therapeutic benefit for mitochondrial cardiomyopathy.
Absolute Event Rate: 1.69% vs 0.95%
p-value: p=0.004
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.
Arakawa et al. (Fri,) conducted a observational in Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) (n=12). L-arginine vs. Healthy controls / Baseline was evaluated on Baseline myocardial efficiency (DP/kmono) (p=0.004). MELAS patients demonstrated significantly greater baseline myocardial efficiency compared to healthy controls (1.69 vs 0.95 x 10^5, P=0.004), with L-arginine infusion enhancing TCA-cycle metabolism in 4 of 6 patients.