TY - JOUR
T1 - Exertional dyspnea in mitochondrial myopathy
T2 - Clinical features and physiological mechanisms
AU - Heinicke, Katja
AU - Taivassalo, Tanja
AU - Wyrick, Phil
AU - Wood, Helen
AU - Babb, Tony G.
AU - Haller, Ronald G.
PY - 2011/10
Y1 - 2011/10
N2 - Exertional dyspnea limits exercise in some mitochondrial myopathy (MM) patients, but the clinical features of this syndrome are poorly defined, and its underlying mechanism is unknown. We evaluated ventilation and arterial blood gases during cycle exercise and recovery in five MM patients with exertional dyspnea and genetically defined mitochondrial defects, and in four control subjects (C). Patient ventilation was normal at rest. During exercise, MM patients had low V O 2peak (28 ± 9% of predicted) and exaggerated systemic O 2 delivery relative to O 2 utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high VE/V O 2peak, (MM = 104 ± 18; C = 42 ± 8, P ≤ 0.001), and VE/VCO 2peak, (MM = 54 ± 9; C = 34 ± 7, P ≤ 0.01); a steeper slope of increase in δVE/ΔVCO 2 (MM = 50.0 ± 6.9; C = 32.2 ± 6.6, P ≤ 0.01); and elevated peak respiratory exchange ratio (RER), (MM = 1.95 ± 0.31, C = 1.25 ± 0.03, P ≤ 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower PaCO2 and standard bicarbonate. However, during 5 min of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. These data indicate that exertional dyspnea in MM is attributable to mitochondrial defects that severely impair muscle oxidative phosphorylation and result in a hyperkinetic circulation in exercise. Exaggerated exercise ventilation is indicated by markedly elevated V E/V O 2, V E/V CO 2, and RER. While lactic acidosis likely contributes to exercise hyperventilation, the fact that ventilation normalizes during recovery from exercise despite increasing metabolic acidosis strongly indicates that additional, exercise-specific mechanisms are responsible for this distinctive pattern of exercise ventilation.
AB - Exertional dyspnea limits exercise in some mitochondrial myopathy (MM) patients, but the clinical features of this syndrome are poorly defined, and its underlying mechanism is unknown. We evaluated ventilation and arterial blood gases during cycle exercise and recovery in five MM patients with exertional dyspnea and genetically defined mitochondrial defects, and in four control subjects (C). Patient ventilation was normal at rest. During exercise, MM patients had low V O 2peak (28 ± 9% of predicted) and exaggerated systemic O 2 delivery relative to O 2 utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high VE/V O 2peak, (MM = 104 ± 18; C = 42 ± 8, P ≤ 0.001), and VE/VCO 2peak, (MM = 54 ± 9; C = 34 ± 7, P ≤ 0.01); a steeper slope of increase in δVE/ΔVCO 2 (MM = 50.0 ± 6.9; C = 32.2 ± 6.6, P ≤ 0.01); and elevated peak respiratory exchange ratio (RER), (MM = 1.95 ± 0.31, C = 1.25 ± 0.03, P ≤ 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower PaCO2 and standard bicarbonate. However, during 5 min of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. These data indicate that exertional dyspnea in MM is attributable to mitochondrial defects that severely impair muscle oxidative phosphorylation and result in a hyperkinetic circulation in exercise. Exaggerated exercise ventilation is indicated by markedly elevated V E/V O 2, V E/V CO 2, and RER. While lactic acidosis likely contributes to exercise hyperventilation, the fact that ventilation normalizes during recovery from exercise despite increasing metabolic acidosis strongly indicates that additional, exercise-specific mechanisms are responsible for this distinctive pattern of exercise ventilation.
KW - Exercise
KW - Hyperventilation
KW - Lactic acidosis
KW - Metaboreflex
KW - Oxidative phosphorylation
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U2 - 10.1152/ajpregu.00001.2011
DO - 10.1152/ajpregu.00001.2011
M3 - Article
C2 - 21813873
AN - SCOPUS:80053626315
SN - 0363-6119
VL - 301
SP - R873-R884
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 4
ER -