The candidate is a clinically trained cardiologist interested in cardiac metabolism and its application to the study of cardiac disease. The goal of the projected research is to provide the candidate with the broad scientific training necessary to pursue this interest as an independent investigator and academic cardiologist. Physiologic measurement of protein turnover in vivo has not been accomplished previously in a non-destructive fashion.
The specific aim of the proposed research involves the development of an isotope dilution technique to study in vivo cardiac amino acid utilization and protein metabolism. The technique will be validated and applied in a conscious dog model, in anticipation of its utilization in clinical investigation. Experimental methods to examine the physiologic regulation of protein metabolism in normal dogs will include the insulin clamp, substrate infusion, and insulin suppression with somatostatin. Alterations in metabolism in animals with diabetes and myocardial ischemia will be studied. Abnormalities in protein and amino acid metabolism may contribute to the abnormal cardiac reserve and cardiomyopathy observed in diabetic patients. Alterations in amino acid and protein metabolism in myocardial ischemia may be important to the rate and degree of recovery from ischemia. Further understanding of the pathophysiology of cardiac protein metabolism may impact directly on the treatment of patients wiht diabetes and those recovering from ischemic insult following reperfusion in acute myocardial infarction. Collaboration between the Divisions of Cardiology and Endocrinology and the Department of Molecular Biology and Biochemistry has established a strong interdisciplinary background at Yale in the area of cardiac and skeletal muscle metabolism. The methods to measure coronary blood flow, cardiac hemodynamics, and both global and regional cardiac performance are available in the Cardiology Division. Techniques to study the effects of insulin and metabolic substrates on protein turnover in the dog have been used in the Endocrine Division. Likewise, expertise in the measurement of high energy phosphate levels by NMR spectroscopy has been developed. This environment will provide the candidate with the solid background training to develop as an independent investigator in the area of cardiac metabolism.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001840-02
Application #
3082225
Study Section
(SRC)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
McNulty, P H; Young, L H; Barrett, E J (1993) Response of rat heart and skeletal muscle protein in vivo to insulin and amino acid infusion. Am J Physiol 264:E958-65
Young, L H; Dahl, D M; Rauner, D et al. (1992) Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart. Circ Res 71:393-400
Young, L H; McNulty, P H; Morgan, C et al. (1991) Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion. J Clin Invest 87:554-60
Revkin, J H; Young, L H; Stirewalt, W S et al. (1990) In vivo measurement of myocardial protein turnover using an indicator dilution technique. Circ Res 67:902-12
Young, L H; Jaffe, C C; Revkin, J H et al. (1990) Metabolic and functional effects of perfluorocarbon distal perfusion during coronary angioplasty. Am J Cardiol 65:986-90
Young, L H; Zaret, B L; Barrett, E J (1989) Physiologic hyperinsulinemia stimulates lactate extraction by heart muscle in the conscious dog. Metabolism 38:1115-9