Chronic elevations in plasma arterial catecholamines are associated with many cardiovascular disease states including heart failure and mitral valve prolapse. Furthermore, these patients often have ischemic heart disease, myocardial dysfunction, trasient hypertension and exercise intolerance. The goal of our studies is to define the changes and mechanisms responsible for alterations in myocardial function, the maintenance of arterial pressure, myocardial hypertrophy and morphometric/ultrastructural changes in the right and left ventricle during prolonged (greater than 28 days) elevations (2000- 4000 pg/ml) in plasma arterial norepinephrine. These goals will be accomplished by instrumenting dogs using general surgical procedure, then allowing them to fully recover. Animals will be studied in the conscious state and then miniosmotic pumps implanted which release norepinephrine for 28 days. Pumps will be reimplanted and studied again during chronic elevations in plasma norepinephrine at 25 day intervals. During this investigatorship we will study the control of myocardial function, the reflex regulation of pressure, myocardial size and cellular alterations in the myocardium. Using morphometric techniques with light and electron microscopy we will attempt to define for the first time in a uniform population of beagle dogs of similar size, age and sex, the microvascular changes and the ultrastructural basis of the hypertrophy which occurs during chronic infusion of norepinephrine. Besides the physiologic and ultrastructural basis of the hypertrophy, we will define the role of the systemic arterial baroreflexes in the maintenance of pressure in dogs with high circulating norepinephrine. The mechanisms of baroreflex regulation under these conditions will be a major focus of these studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036264-03
Application #
3351106
Study Section
Cardiovascular Study Section (CVA)
Project Start
1987-07-01
Project End
1990-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
New York Medical College
Department
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595
Stewart, J M; Patel, M B; Wang, J et al. (1992) Chronic elevation of norepinephrine in conscious dogs produces hypertrophy with no loss of LV reserve. Am J Physiol 262:H331-9
Stewart, J M; Dean, R; Brown, M et al. (1992) Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs. Circ Res 70:724-32
Belloni, F L; Wang, J; Hintze, T H (1992) Adenosine causes bradycardia in pacing-induced cardiac failure. Circulation 85:1118-24
Wang, J; Zeballos, G A; Kaley, G et al. (1991) Dilation and constriction of large coronary arteries in conscious dogs by endothelin. Am J Physiol 261:H1379-86
Patel, M B; Stewart, J M; Loud, A V et al. (1991) Altered function and structure of the heart in dogs with chronic elevation in plasma norepinephrine. Circulation 84:2091-100
Wang, J; Ochoa, M; Patel, M B et al. (1991) Carotid baroreceptor function in dogs with chronic norepinephrine infusion. Hypertension 17:745-54
Belloni, F L; Hintze, T H (1991) Glibenclamide attenuates adenosine-induced bradycardia and coronary vasodilatation. Am J Physiol 261:H720-7
Stewart, J M; O'Dea, D J; Shapiro, G C et al. (1991) Atrial compliance determines the nature of passive atrial stretch and plasma atrial natriuretic factor in the conscious dog. Cardiovasc Res 25:784-92
Stewart, J M; Wang, J; Singer, A et al. (1990) Regulation of plasma ANF after increases in afterload in conscious dogs. Am J Physiol 259:H1736-42
Patel, M B; Hintze, T H (1990) Atriopeptin 24 regulates myocardial function via Frank-Starling mechanism in conscious dogs. Am J Physiol 258:H183-90

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