verbatim): Older age is associated with a marked increase in cardiac morbidity and mortality following a myocardial infarction regardless of the administration of thrombolytic therapy, an early invasive approach, and the use of aspirin, ACE-inhibitors and beta-blockers. A significant proportion of these adverse outcomes are related to the cardiac consequences of the infarct itself, namely left ventricular dysfunction, cardiogenic shock, and congestive heart failure; in spite of the fact that indices of infarct size tend to decrease with age. This proposal examines the broad hypothesis that the age-associated physiologic changes in vascular and ventricular properties we previously studied and described, and most importantly increased stiffness, alter the substrate upon which a myocardial infarction is superimposed so as to increase the likelihood of left ventricular dysfunction, and clinical congestive heart failure in older patients. More specifically, we propose to use sophisticated techniques and models to characterize vascular load (Ea-arterial elastance) and its interaction with ventricular performance (Ees- left ventricular end-systolic elastance) in older post-infarction patients and to relate age-associated changes in ventricular-vascular coupling (Ea/Ees relationship) in these patients to six-month changes in left ventricular function and to clinical outcomes. Finally, we propose to test the hypothesis that decreasing arterial stiffness results in an improvement in 6-month outcomes in a prospective, randomized clinical trial employing L-arginine, an agent that decreases vascular load via mechanisms other than those influenced by routine post-infarction therapies. We anticipate that the study findings will suggest the use of new evaluation and therapeutic strategies, which will significantly decrease the age associated mortality and morbidity in post-infarction patients.
| McLean, Rhondalyn C; Hirsch, Glenn A; Becker, Lewis C et al. (2011) Polymorphisms of the beta adrenergic receptor predict left ventricular remodeling following acute myocardial infarction. Cardiovasc Drugs Ther 25:251-8 |
