Exercise responses in patients with an enzyme deficiency in the mitochondrial respiratory chain

Abstract

Responses to exercise were obtained in six patients with a biochemically diagnosed enzyme deficiency at the level of NADH-CoQ reductase. The responses were compared with those of a control group, consisting of fourteen patients with inexplicable dyspnoea or muscle pain during exercise, for which no firm diagnosis could be established and of which the exercise responses were in the normal range. Metabolic, ventilatory and cardiological variables such as oxygen uptake (V̇O2), minute ventilation (V̇E), respiratory exchange ratio (R), heart rate (HR) and difference in blood lactate or base-excess (BE) between rest and maximal workload were measured during cycle ergometry from samples obtained in the last minutes of four minute periods, in which the load increased stepwise by 30 W per four minutes. The threshold of lactate metabolism (T(lact)) was assumed to be equal to the threshold determined both by the V̇O2 at which the V̇E versus V̇O2 response started to deviate from a straight line and the ventilatory equivalent for oxygen (V̇E/V̇O2) showed a minimum (T(vent)). T(vent) was estimated from the mean of these values, obtained by linear and parabolic regression analysis respectively. In the patient group, mean values for symptom limited maximal V̇O2 (V̇O2,(max,sl); % of V̇O2,(max,ref)), T(vent) (% of V̇O2,(mac,ref)) and R at maximal workload were 43, 17 and 1.23 against 85, 47 and 1.06 for the same variables in the control group, respectively. The differences were highly significant (p < 0.001; p < 0.005 for mean R difference). Mean maximal HR and mean change in blood lactate or BE were not significantly different in the two groups. Considering the physiological mechanisms influencing the exercise responses, including the threshold of lactate metabolism, we hypothesize that the limited work performance in the patient group is given by a limitation of the oxidative capacity of the respiratory chain by the enzyme deficiency, giving an early energy sypply by anaerobic glycolysis. Our investigation stresses the validity of exercise testing as an investigative strategy in neuromuscular disorders.