MYOCARDIAL HYPERTROPHY AND FAILURE IN CONSCIOUS DOGS

Project Details

Description

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.
StatusFinished
Effective start/end date1/1/845/31/87

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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