TY - JOUR
T1 - Impaired cardiac reserve and severely diminished skeletal muscle o 2 utilization mediate exercise intolerance in barth syndrome
AU - Spencer, Carolyn T.
AU - Byrne, Barry J.
AU - Bryant, Randall M.
AU - Margossian, Renee
AU - Maisenbacher, Melissa
AU - Breitenger, Petar
AU - Benni, Paul B.
AU - Redfearn, Sharon
AU - Marcus, Edward
AU - Cade, W. Todd
PY - 2011/11
Y1 - 2011/11
N2 - Impaired cardiac reserve and severely diminished skeletal muscle O2 utilization mediate exercise intolerance in Barth syndrome. Am J Physiol Heart Circ Physiol 301: H2122-H2129, 2011. First published August 26, 2011; doi:10.1152/ajpheart.00479.2010.-Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O2 extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O2 extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O2 extraction. Adjusting for age, peak O2 consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg _1·min _1, P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O 2 saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: -5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS.
AB - Impaired cardiac reserve and severely diminished skeletal muscle O2 utilization mediate exercise intolerance in Barth syndrome. Am J Physiol Heart Circ Physiol 301: H2122-H2129, 2011. First published August 26, 2011; doi:10.1152/ajpheart.00479.2010.-Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O2 extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O2 extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O2 extraction. Adjusting for age, peak O2 consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg _1·min _1, P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O 2 saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: -5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS.
KW - Cardiolipin
KW - Cardiomyopathy
KW - Congenital
KW - Mitochondria
UR - http://www.scopus.com/inward/record.url?scp=80355129941&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00479.2010
DO - 10.1152/ajpheart.00479.2010
M3 - Article
C2 - 21873497
AN - SCOPUS:80355129941
SN - 0363-6135
VL - 301
SP - H2122-H2129
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -