Large animal models of left ventricular hypertrophy (LVH) and cardiac failure are associated with alterations of myocardial high energy phosphate (HEP) content and abnormalities of oxidative phosphorylation regulation. Concentric LVH secondary to pressure overload can result in loss of myocardial ATP, a decrease of the phosphocreatine (PCr)/ATP ratio, and an increase of calculated free ADP; these changes are, at least in part, the result of alterations in the regulation of oxidative phosphorylation, but can be aggravated by impaired blood flow to the subendocardium during increased cardiac workloads. Eccentric LVH resulting from volume overload produces only modest reductions of the myocardial PCr/ATP ratio which are not worsened during increases of cardiac work. Post-infarction left ventricular remodeling is associated with a decrease of the myocardial PCr/ATP ratio that is most marked in animals that develop overt congestive heart failure. The depressed PCr/ATP ratio and ATP content in hypertrophied hearts are not the result of persistent myocardial hypoperfusion, since they are not corrected by pharmacologic coronary vasodilation. Furthermore, the additional decrease of myocardial PCr/ATP which occurs during high workloads in hypertrophied as well as in normal hearts occur without evidence of myoglobin desaturation, indicating that these changes cannot be ascribed to oxygen insufficiency. There is some evidence that impairment of long chain fatty acid uptake contributes to HEP abnormalities in hypertrophied or failing hearts. Furthermore, alterations in creatine kinase isoform expression in hypertrophied or failing hearts may result in higher levels of free ADP that could contribute to the observed HEP abnormalities.
Bibliographical noteFunding Information:
This work was supported by U.S. Public Health Service Grants HL21872, HL50470, HL58067, HL61353. Dr. Zhang is recipient of an Established Investigator Award from the American Heart Association.
- Creatine kinase
- Heart failure
- High energy phosphates
- P NMR spectroscopy