We propose to examine circumferential flow-function, relationships using two-dimensional echocardiography (2D echo) and radioactive microsphere techniques in ischemic and infarcted conscious dog models. Although previous studies using unidimensional techniques have examined flow-function relationships in the normal and ischemic myocardium, the mapping of these relationships into a two-dimensional """"""""slice"""""""" model of the heart has not yet been performed. Since most clinical diagnostic imaging modalities now display the heart in two-dimensions, precise mapping of 2D flow-function relationships has important clinical significance in interpreting the results of commonly used cardiac imaging modalities. In the regionally ischemic heart, zones adjacent to the central ischemic area have been noted to be normally perfused, but functionally abnormal; however, the size and hemodynamic properties of this """"""""functional"""""""" border zone are not well understood. In the infarcted heart, regional recovery occurs with variability but flow-function relations during this recovery process are poorly understood. In the reperfused heart, a """"""""no-reflow"""""""" phenomenon may occur with evidence of a """"""""stunned"""""""" myocardium; the interrelationships of perfusion and function in this setting have not been completely evaluated. In the hypertrophied heart, regional ischemia may produce a larger hypoperfused area and extent of dysfunction compared to the nonhypertrophied state; these perfusion and functional abnormalities may bear significantly on the increased mortality in hypertrophic disease. In this proposal, we will examine these issues and specifically: 1) measure the spatial extent of the functional border zone, and study the effect of loading and linotropic interventions, 2) study circumferential flow-function relations during functional recovery following completed infarction, 3) examine the circumferential flow-function profiles early and late following coronary reflow, and 4) evaluate the effect of regional ischemia in the hypertrophied heart. We will accomplish this by producing and analysing circumferential flow-function maps derived from cross-sectional """"""""slice"""""""" data from wall thickening by 2D echo and myocardial blood flow of corresponding regions using radioactive microspheres. Thus, this proposal should have direct clinical relevance to: 1) the sizing of myocardial ischemia and infarction by two-dimensional functional parameters, 2) understanding mechanisms of functional recovery following coronary occlusion and myocardial infarction, 3) interrelationships of flow and function in the reperfused heart, and 4) the effect of myocardial ischemia in the hypertrophied heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034691-02
Application #
3347866
Study Section
Cardiovascular Study Section (CVA)
Project Start
1986-12-01
Project End
1990-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Lockyer, J M; Colladay, J S; Alperin-Lea, W L et al. (1998) Inhibition of nuclear factor-kappaB-mediated adhesion molecule expression in human endothelial cells. Circ Res 82:314-20
Tenaglia, A N; Buda, A J; Wilkins, R G et al. (1997) Levels of expression of P-selectin, E-selectin, and intercellular adhesion molecule-1 in coronary atherectomy specimens from patients with stable and unstable angina pectoris. Am J Cardiol 79:742-7
Lefer, D J; Flynn, D M; Buda, A J (1996) Effects of a monoclonal antibody directed against P-selectin after myocardial ischemia and reperfusion. Am J Physiol 270:H88-98
Lefer, D J; Flynn, D M; Anderson, D C et al. (1996) Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following ischemia and reperfusion. Am J Physiol 271:H2421-9
Pabla, R; Buda, A J; Flynn, D M et al. (1995) Intracoronary nitric oxide improves postischemic coronary blood flow and myocardial contractile function. Am J Physiol 269:H1113-21
Wood, J C; Barry, D T (1994) Quantification of first heart sound frequency dynamics across the human chest wall. Med Biol Eng Comput 32:S71-8
Wood, J C; Festen, M P; Lim, M J et al. (1994) Regional effects of myocardial ischemia on epicardially recorded canine first heart sounds. J Appl Physiol 76:291-302
Lefer, D J; Flynn, D M; Phillips, M L et al. (1994) A novel sialyl LewisX analog attenuates neutrophil accumulation and myocardial necrosis after ischemia and reperfusion. Circulation 90:2390-401
Wood, J C; Buda, A J; Barry, D T (1992) Time-frequency transforms: a new approach to first heart sound frequency dynamics. IEEE Trans Biomed Eng 39:730-40
Lim, M J; Karolle, B L; Wood, J C et al. (1992) Ischemic expansion during acute myocardial infarction and reversal by coronary reperfusion. Am Heart J 123:1456-63

Showing the most recent 10 out of 28 publications