Skeletal muscle mitochondrial function and exercise capacity in HIV-infected patients with lipodystrophy and elevated p-lactate levels

• Published in: AIDS (London) Vol. 16; no. 7; pp. 973 - 982
• Main Authors: RØGE, Birgit T, CALBET, José A. L, MØLLER, Kirsten, ULLUM, Henrik, HENDEL, Helle W, GERSTOFT, Jan, PEDERSEN, Bente K
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 03-05-2002
• Subjects: 3-Hydroxyacyl CoA Dehydrogenases - analysis; Acidosis, Lactic - etiology; Acidosis, Lactic - prevention & control; Adult; Aged; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacology; Antiretroviral Therapy, Highly Active - adverse effects; Biological and medical sciences; Biopsy; Body Composition; Citrate (si)-Synthase - analysis; Exercise Test; Exercise Tolerance; Female; Glycogen - analysis; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - metabolism; Human viral diseases; Humans; Infectious diseases; Lactates - blood; Lipodystrophy - chemically induced; Lipodystrophy - metabolism; Male; Medical sciences; Middle Aged; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - physiology; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Nucleotides - analysis; Oxygen Consumption; Pyruvates - blood; Reverse Transcriptase Inhibitors - adverse effects; Reverse Transcriptase Inhibitors - pharmacology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Physical exercise; Human; Immunopathology; Skin disease; Cell function; Hyperlactacidemia; Pathogenesis; Oxygen consumption; AIDS; Striated muscle; Immune deficiency; Mitochondrial disorder; Infection; Metabolic disorder; Mitochondria; Viral disease; Lipodystrophy; Adipose tissue disorders; Lactic acid
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200205030-00003

To investigate the skeletal muscle mitochondrial function in HIV-infected patients with lipodystrophy or elevated p-lactate levels.
Eight HIV patients treated with highly active antiretroviral therapy, with lipodystrophy or elevated p-lactate, and eight healthy controls were exposed to incremental exercise until exhaustion.
Blood samples and gas analysis were performed at rest, during exercise and in recovery. Oxygen consumption, workload and blood lactate were assessed. Before and immediately after exercise muscle biopsies were obtained, in which citrate synthase (CS), hydroxyacyl-coenzyme A dehydrogenase (HD), glycogen and nucleotides were measured.
Maximal workload was significantly lower in patients compared with controls [171 Watt (88-206) versus 235 Watt (118-294) P = 0.05]. A trend towards lower maximal oxygen consumption (VO(2max)) was detected in patients [2136 ml/min (1221-2598) versus 2985 ml/min (1506-3959) P = 0.11]. Patients had significantly elevated levels of blood lactate at rest [1.55 mmol/l (1-2.5) versus 0.8 mmo/l (0.37-1.1) P < 0.01), but no significant difference in maximal blood-lactate values was found. The decline in blood lactate in the recovery period was similar between groups. There was no significant difference in CS, HD, glycogen or nucleotides.
The significantly lower working capacity and the trend towards reduced VO(2max) in patients could be caused by mitochondrial dysfunction, but may also be caused by impaired physical fitness. The similar levels of nucleotides, CS, HD, and glycogen and the normal increase in blood lactate during exercise indicates a normal oxidative phosphorylation. No evidence of serious damage to skeletal muscle mitochondrial function was found.