In patients with recent myocardial infarction, determining the amount of myocardium salvaged and that is still at risk for further ischemic injury, are of critical importance for evaluating the efficacy of therapies designed to terminate the ischemic event acutely, to treat its sequelae, and to guide further diagnostic and therapeutic interventions. Results of studies in experimental animals suggest that myocardium subjected to a prolonged but fully reversible ischemic insult is less efficient (i.e., it consumes more oxygen to perform a given level of work) than normal myocardium. Accordingly, the overall objective of this project is to measure the adequacy of energy transduction in human myocardium subjected to prolonged ischemia in order to better characterize the uncoupling of myocardial perfusion, metabolism and function particularly in relation to the long-term functional recovery in such tissue. Using approaches developed and validated at our institution that utilize two-dimensional echocardiography to provide indirect estimates of regional myocardial external work and PET with 11C-acetate to quantify regional MVO2, an estimate of regional myocardial efficiency in human subjects will be developed. The accuracy of the method will be validated against independent measurements of left ventricular external work and its reproducibility documented in normal human subjects and in patients with coronary artery disease. Regional myocardial efficiency will then be measured in patients with recent myocardial infarction who have a patent infarct-related artery at the time of coronary angiography and who subsequently either are treated medically or undergo percutaneous transluminal coronary angioplasty. Estimates of regional myocardial efficiency will be performed under resting conditions. Estimates of regional efficiency will also be obtained during the intravenous infusion of dobutamine, to assess how inotropic stimulation affects the efficiency of myocardium following prolonged ischemia and to glean insights into the amount of functional and metabolic reserve displayed by such tissue in relation to its long-term functional recovery. These measurements will provide a better understanding of the mechanisms responsible for the uncoupling of flow, metabolism, and mechanical function that is observed typically in postischemic myocardium. Accurate estimation of the adequacy of the transfer of energy will facilitate the evaluation of efficacy of therapies designed to augment mechanical function by improving the balance between oxygen supply and demand. Measurements of regional myocardial efficiency performed under resting conditions and during inotropic stimulation will help clarify how regional mechanical function can improve in the setting of fixed levels of perfusion and the extent to which such stimulation may be detrimental to long-term myocardial salvage. Furthermore, such measurements may possibly identify new physiologic determinants and descriptors of the capacity for functional recovery after a prolonged ischemic insult.
| Lee, H H; Davila-Roman, V G; Ludbrook, P A et al. (1997) Dependency of contractile reserve on myocardial blood flow: implications for the assessment of myocardial viability with dobutamine stress echocardiography. Circulation 96:2884-91 |
