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Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms.
MedLine Citation:
PMID:  21813873     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 VO(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/VO(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 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 PaCO(2) and standard bicarbonate. However, during 5 minutes of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. Conclusion: 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 VE/VO(2), VE/VCO(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.
Authors:
Katja Heinicke; Tanja Taivassalo; Phil Wyrick; Helen Wood; Tony G Babb; Ronald G Haller
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-3
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  -     ISSN:  1522-1490     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Texas Health Presbyterian Hospital Dallas.
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