• Goldman, Steven (PI)

Project: Research project

Grant Details


Myocardial infarction, especially if large and transmural, results in
alterations in ventricular structure involving both the infarcted and
noninfarcted myocardium. These alterations, which have been termed
"ventricular remodeling," affect ventricular performance and survival.
Compared to younger patients, the aged have more left ventricular
dysfunction and worse long-term survival. The explanation for this is
not clear. However, data in the senescent rat and in the pressure- and
volume-overloaded aged rat suggest that compensatory myocardial
hypertrophy sufficient to normalize wall stress is the major determinant
of ventricular remodeling and function. We have preliminary data in aged
rats which shows that, compared to younger rats, aged rats with the same
size infarctions have more ventricular dilatation and less hypertrophy in
the noninfarcted myocardium. These data support our hypothesis that: "In aged rats, inadequate compensatory hypertrophy of the noninfarcted
myocardium results in extensive remodeling and deterioration in left
ventricular function." This proposal outlines a novel approach to improving ventricular function
by augmenting hypertrophy in the noninfarcted myocardium. The hypothesis
is that this hypertrophy will reduce the extent of ventricular remodeling
and its sequelae, i.e., ventricular dilatation, LV dysfunction, and
increased mortality. The coronary artery ligation model of myocardial
infarction will be used in 8 and 18 month old 344 X BN rats. One month
after infarction, we will examine global cardiac function and analyze
anatomic-morphologic components of left ventricular geometry to assess
wall stress and remodeling. To create hypertrophy in the noninfarcted
myocardium, we will use agents that inhibit fatty acid oxidation or that
stimulate glucose (lactate) oxidation. The first agent will be
tetradecylglycidic acid (TDGA), which we have shown will cause
hypertrophy in the noninfarcted myocardium of normal Sprague-Dawley rats.
This approach is designed to alter the process of ventricular remodeling
post-infarction in the aged.
Effective start/end date1/1/9312/31/95


  • National Institutes of Health: $163,310.00


  • Medicine(all)


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