Project: Research project

Project Details


Approximately 1% of live births are complicated with some sort of
cardiovascular malformation. This accounts for 80 to 90% of pediatric
patients under 1 year of age that develop congestive heart failure. It is
thus important to understand the physiology of heart failure in the infant
and fetus. Cardiac hypertrophy is an important adaptive mechanisms that
enables the heart to compensate for overload and is a process that precedes
heart failure. This proposal focuses on the cellular abnormalities that
occur during hypertrophy of the fetal heart. The purpose of this
application is to determine whether the electrical and inotropic properties
of the heart are altered in an animal model of fetal sheep left ventricular
cardiac hypertrophy. The Specific Aims of this study are: 1) to determine
whether the action potential and inotropic state of the heart are altered
in the fetal hypertrophic model; 2) to determine whether potassium channel
function is altered in the fetal hypertrophic model; 3) to determine
whether Ca2+ channel function is altered in the fetal hypertrophic model;
4) to biochemically determine the number of beta-adrenergic and
dihydropyridine (L-type Ca channel) receptor sites in the fetal
hypertrophic model; 5) to determine the ontogeny of the ionic currents in
the developing sheep heart at 80, 120, 135, 145 and 155 days post-
conception. Aim 1 will provide important information about modulation of
the force-interval relationship by beta-adrenergic stimulation in the
hypertrophic model and whether the action potential is prolonged as in
adult models of hypertrophy. Aims 2 and 3 will provide information about
whether the individual potassium and calcium currents, that underlie the
action potential and effect excitation-contraction coupling, are altered in
the fetal hypertrophic model. Aim 4 will determine whether Ca channel and
beta-adrenergic receptor densities are altered and provide information on
whether desensitization or functional uncoupling of beta-adrenergic
receptors has occurred in the hypertrophic model. Aim 5 will test the
hypothesis that load induced hypertrophy of fetal hearts follows a
different cellular program than normal development. This study will
provide new and valuable information on the plasticity of ion channels in
the fetal heart.
Effective start/end date4/1/923/31/97


  • National Institutes of Health: $194,356.00
  • National Institutes of Health: $199,846.00


  • Medicine(all)


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