The overall goal of this study is to examine modifications in ventricular performance, coronary perfusion, myocardial energy metabolism and cardiac and coronary vascular adrenergic receptor activity in experimental models of chronic pressure overload right ventricular (RV) and left ventricular (LV) hypertrophy and failure. Measurements of cardiac pressures and dimensions, aortic pressure and coronary blood flow and diameter will be radiotelemetered from conscious, chronically instrumented dogs. Three models will be studied: RV pressure overload hypertrophy and failure; LV pressure overload hypertrophy (subcoronary and supracoronary banding). The following specific goals will be pursued. 1) To determine the changes in myocardial function that occur with the development of stable cardiac hypertrophy and progression to failure. 2) To determine the accompanying coronary vascular adaptations, and particuarly the difference in vasodilator capacity of the hypertrophied left ventricle with subcoronary vs supracoronary banding. 3) To determine if abnormalities in cardiac and coronary vascular control mechanisms can be elicited with stress, e.g., severe spontaneous exercise, pacing, sympathomimetic amines. 4) To determine the extent to which the alterations in coronary and cardiac control mechanisms are associated with changes in a) adrenergic receptor binding and affinity, b) myocardial energy metabolism, c) diastolic mechanical properties of the hypertrophied hearts. 5) To determine the extent to which alpha adrenergic control of the coronary circulation is depressed, and specifically, the extent to which carotid chemoreceptor reflex induced coronary constriction is altered in the presence of RV hypertrophy and failure. 6) To determine whether the depressed coronary vascular response to chemoreceptor stimulation is specific for the coronary vessels, or whether it also extends to derangements in responses of cardiac contractility, cardiac cycle length, and iliac vascular resistance. These studies are designed to elucidate alterations in fundamental myocardial coronary vascular and cellular control mechanisms with the development of myocardial hypertrophy and progression to cardiac failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033743-04
Application #
3345929
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1984-01-01
Project End
1987-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Longabaugh, J P; Vatner, D E; Vatner, S F et al. (1988) Decreased stimulatory guanosine triphosphate binding protein in dogs with pressure-overload left ventricular failure. J Clin Invest 81:420-4
Knight, D R; Thomas Jr, J X; Randall, W C et al. (1987) Effects of left circumflex coronary flow transducer implantation on posterior wall innervation. Am J Physiol 252:H536-9
Fujii, A M; Vatner, S F (1987) Baroreflex mechanisms buffering alpha-adrenergic agonists in conscious dogs. Am J Physiol 253:H728-36
Kirby, D A; Vatner, S F (1987) Enhanced responsiveness to carotid baroreceptor unloading in conscious dogs during development of perinephritic hypertension. Circ Res 61:678-86
Fujii, A M; Vatner, S F; Serur, J et al. (1986) Mechanical and inotropic reserve in conscious dogs with left ventricular hypertrophy. Am J Physiol 251:H815-23
Vatner, D E; Lavallee, M; Amano, J et al. (1985) Mechanisms of supersensitivity to sympathomimetic amines in the chronically denervated heart of the conscious dog. Circ Res 57:55-64
Fujii, A M; Vatner, S F (1985) Direct versus indirect pressor and vasoconstrictor actions of angiotensin in conscious dogs. Hypertension 7:253-61
Vatner, D E; Kirby, D A; Homcy, C J et al. (1985) beta-Adrenergic and cholinergic receptors in hypertension-induced hypertrophy. Hypertension 7:I55-60
Knight, D R; Kirby, D A; Vatner, S F (1985) Effects of a calcium channel blocker on cardiac output distribution in conscious hypertensive dogs. Hypertension 7:380-5
Fujii, A M; Vatner, S F (1985) Autonomic mechanisms regulating myocardial contractility in conscious animals. Pharmacol Ther 29:221-38