Reduced mitochondrial adenosine triphosphate synthesis in skeletal muscle in patients with Child-Pugh class B and C cirrhosis

Patients with cirrhosis of the liver often complain of tiredness and a lack of strength at physical exercise. Other investigators have found that muscle strength, work capacity, and maximal oxygen consumption are reduced in cirrhosis. We hypothesized that mitochondrial maximal rate of ATP synthesis in skeletal muscle may be impaired in these patients. This was tested with P-31 nuclear magnetic resonance spectroscopy in anterior tibial muscle of cirrhotic patients and healthy controls at rest, during exercise, and subsequent recovery, In patients with Child-Pugh class B and C cirrhosis resting PCr/P-i ratio (8.3 +/- 1.0; n = 7) was lower than in patients with Child-Pugh class A cirrhosis (12.1 +/- 2.1; n 7) and controls (11.7 +/- 1.1; n = 6; P = .03), while the resting P-i/gamma ATP ratio was higher in Child-Pugh class B and C patients (0.43, 0.30, and 0.27, respectively; P = .03). Maximal rate of mitochondrial adenosine triphosphate (ATP) synthesis (V,,) as calculated from the initial rate of phosphocreatine (PCr) recovery after work was lower in Child-Pugh class B and C cirrhosis (0.189 mmol/L/s +/- 0.034) than in both Child-Pugh class A patients (0.4 02 mmol/L/s +/- 0.103) and controls (0.425 mmol/L/s +/- 0.064; P = .01.). V-max was significantly correlated to intracellular free [Mg2+] obtained from the 31P nuclear magnetic resonance (NMR) spectra (P = 0.003). Insufficient oxygen delivery did not seem a likely cause of reduced ATP synthesis in the patients. These findings suggest either a decreased number of mitochondria in skeletal muscle of the cirrhotic patient in Child-Pugh class B and C or a defective mitochondrial function that could be related to low intracellular free [Mg2+].