This proposal outlines the investigation of the influence of physiologic elevations of insulin and the major myocardial fuel substrates -- free fatty acids (FFA), glucose, and amino acids (AA) -- on their respective myocardial balances, and on indices of systolic and diastolic cardiac performance in vivo in experimental and clinical models of regional myocardial ischemia. Specific questions include: (1) Is myocardial alanine production a reliable marker of regional myocardial ischemia? Is myocardial alanine production in ischemia influenced by the arterial concentrations of AA, insulin, glucose or FFA? (2) Does regional myocardial ischemia affect the uptake of branched chain amino acids (BCAA)? Is the uptake of BCAA in regional ischemia influenced in vivo by physiologic increases in insulin, BCAA, glucose, or FFA? (3) Do ammonia, glutamine, and alanine account for most nitrogen loss from the ischemic myocardium, or are other amino acids released in ischemic myocardium? (4) Does the presence of diabetes in patients with coronary artery disease (CAD) or in streptozotocin treated dogs influence the balance of AA, glucose, FFA or the sensitivity of the ischemic myocardium to the glucose stimulating effects of insulin? (5) Is impairment of global and regional cardiac performance (left ventricular ejection fraction, regional left ventricular wall thickening and motion, and coronary blood flow) during myocardial ischemia influenced by physiologic increments in vivo of insulin, AA, FFA and glucose? The applicant has been broadly trained in clinical cardiology, and has obtained some research experience in studies of myocardial metabolism in the conscious normal and diabetic dog and in patients with CAD. The proposed research plan enable the candidate to have an intensive supervised experience in cardiovascular research, to become a more highly trained academic cardiologist, and to develop a career as an independent investigator. The facilities, collaborators and quality of supervision available to the applicant create an effective and supportive environment that should enable the applicant to accomplish the goals set forth in this proposal. Thus, a propitious academic environment is in place at The University of Rochester to assist the applicant in the successful completion of the proposed research.
| Cody, R J; Kubo, S H; Laragh, J H et al. (1992) Cardiac secretion of atrial natriuretic factor with exercise in chronic congestive heart failure patients. J Appl Physiol 73:1637-43 |
| Welle, S; Schwartz, R G; Statt, M (1991) Reduced metabolic rate during beta-adrenergic blockade in humans. Metabolism 40:619-22 |
