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Human myocardial adenosine triphosphatase activities in health and heart failure
D V Unverferth1, S W Lee, E T Wallick
1Department of Medicine, Ohio State University College of Medicine, Columbus 43210.
Insights
Myocardial adenosine triphosphatase (ATPase) activity, particularly total and mitochondrial forms, declines with worsening heart failure. This reduction in ATPase activity may perpetuate cardiac dysfunction by impairing energy production.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Dilated cardiomyopathy is a significant cause of heart failure.
- Myocardial adenosine triphosphatase (ATPase) enzymes are crucial for cardiac energy metabolism.
- Understanding ATPase activity in heart failure is essential for elucidating disease mechanisms.
Purpose of the Study:
- To compare myocardial ATPase activities between normal individuals and patients with dilated cardiomyopathy.
- To investigate the relationship between ATPase activity and factors like age, heart failure severity, and digitalis treatment.
Main Methods:
- Endomyocardial biopsies were obtained from 32 subjects (6 normal, 26 with dilated cardiomyopathy).
- Analysis of total, mitochondrial, Na+-K+, Ca++, and Mg++ ATPase activities.
- Correlation of ATPase activities with clinical parameters including left ventricular ejection fraction and echocardiography.
Main Results:
- Total and mitochondrial ATPase activities significantly correlated with left ventricular ejection fraction (p=0.0001).
- Residual Mg++ ATPase activity showed a weak correlation with ventricular function (p=0.05).
- Na+-K+ ATPase activity was significantly lower in patients treated with digitalis (p=0.01).
Conclusions:
- Progressive ventricular dysfunction in dilated cardiomyopathy is associated with reduced total, mitochondrial, and Mg++ ATPase activity.
- Depressed mitochondrial ATPase activity may contribute to perpetuating heart failure by limiting adenosine triphosphate production.
- Further research into ATPase activity could offer insights into the pathogenesis of cardiac failure.
Abstract:
This study was designed to determine: (1) the myocardial adenosine triphosphatase (ATPase) activities of normal humans and patients with dilated cardiomyopathy and (2) whether ATPase activity is related to age, cause and severity of heart failure, and digitalis therapy. Endomyocardial biopsies were performed in 32 subjects. Results from six were normal. Ventricular failure in the other 26 was idiopathic (n = 15), familial (n = 3), alcohol induced (n = 5), or related to doxorubicin therapy (n = 3). The biopsies were analyzed for total, mitochondrial, Na+-K+, Ca++, and Mg++ ATPase activities. Total and mitochondrial ATPase activities correlated with left ventricular ejection fraction (r = 0.65 and 0.67, respectively; both p = 0.0001). Residual Mg++ ATPase activity correlated weakly with ventricular function as measured by echocardiography (p = 0.05). Na+-K+ ATPase activity was depressed in patients receiving digitalis (p = 0.01). These results suggest that progressive ventricular dysfunction may be associated with a progressive loss of total ATPase, mitochondrial ATPase and, to a lesser extent, Mg++ ATPase activity. Although depressed mitochondrial ATPase activity is not likely to be the primary cause of ventricular dysfunction, it could perpetuate failure by leading to inadequate production of adenosine triphosphate. Further study of ATPase activities may provide additional insight into the pathogenesis of cardiac failure.