{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:06:21Z","timestamp":1791558381934,"version":"4.3.4"},"reference-count":61,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p> 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\u0307o<jats:sub>2peak<\/jats:sub> (28 \u00b1 9% of predicted) and exaggerated systemic O<jats:sub>2<\/jats:sub> delivery relative to O<jats:sub>2<\/jats:sub> utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high V\u0307e\/V\u0307o<jats:sub>2peak<\/jats:sub>, (MM = 104 \u00b1 18; C = 42 \u00b1 8, P \u2264 0.001), and V\u0307e\/V\u0307co<jats:sub>2peak<\/jats:sub><jats:sub>,<\/jats:sub> (MM = 54 \u00b1 9; C = 34 \u00b1 7, P \u2264 0.01); a steeper slope of increase in \u0394V\u0307e\/\u0394V\u0307co<jats:sub>2<\/jats:sub> (MM = 50.0 \u00b1 6.9; C = 32.2 \u00b1 6.6, P \u2264 0.01); and elevated peak respiratory exchange ratio (RER), (MM = 1.95 \u00b1 0.31, C = 1.25 \u00b1 0.03, P \u2264 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower Pa<jats:sub>CO<jats:sub>2<\/jats:sub><\/jats:sub> 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\u0307e\/V\u0307o<jats:sub>2<\/jats:sub>, V\u0307e\/V\u0307co<jats:sub>2<\/jats:sub>, 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. <\/jats:p>","DOI":"10.1152\/ajpregu.00001.2011","type":"journal-article","created":{"date-parts":[[2011,8,4]],"date-time":"2011-08-04T02:06:03Z","timestamp":1312423563000},"page":"R873-R884","source":"Crossref","is-referenced-by-count":41,"title":["Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms"],"prefix":"10.1152","volume":"301","author":[{"given":"Katja","family":"Heinicke","sequence":"first","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, Texas;"},{"name":"Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Taivassalo","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Wyrick","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Wood","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, Texas;"},{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; 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