Abnormal ATP turnover in rat leg muscle during exercise and recovery following myocardial infarction.
OBJECTIVE
Clinical and animal studies show increased acidification of skeletal muscle during exercise in heart failure, implying increased anaerobic metabolism, and impaired recovery from exercise, implying defective oxidative function. This study aimed to define the quantitative relationship between these changes in exercise and recovery and relate skeletal muscle bioenergetics to cardiovascular function.


METHODS
Wistar rats were studied four weeks after myocardial infarction or a sham operation. 31P magnetic resonance spectroscopy of the hind leg muscle was used to estimate rates of oxidative and non-oxidative ATP synthesis from changes in pH and phosphocreatine concentration during sciatic nerve stimulation and to estimate the maximum rate of mitochondrial ATP synthesis from the kinetics of phosphocreatine recovery after stimulation.


RESULTS
Following myocardial infarction, cardiac function was abnormal, with evidence of left ventricular hypertrophy, failure, and diminished arterial pressure. There was impaired phosphocreatine recovery, suggesting an approximate halving of the maximum rate of mitochondrial ATP synthesis.


CONCLUSIONS
The response to exercise of the infarct group was abnormal and was quantitatively consistent with the reduced maximum rate of mitochondrial ATP synthesis inferred from recovery, the oxidative deficit during exercise being made up by increased glycogenolysis, causing sufficient acidification to prevent an appropriate increase in [ADP].
Thompson
C H
CH
MRC Biochemical and Clinical Magnetic Resonance Unit, Oxford Radcliffe Hospital, United Kingdom.
Kemp
G J
GJ
Rajagopalan
B
B
Radda
G K
GK
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008929:Mitochondria, Heart / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism*; D005082:Physical Exertion / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D000255:Adenosine Triphosphate