BIOENERGETIC STUDIES OF REMODELED MYOCARDIUM

University Of Minnesota Twin Cities, Minneapolis MN

Investigators

Abstract

DESCRIPTION (adapted from the applicant's abstract): Recent studies from the applicant's laboratory have suggested that in normal myocardium perfusion limits maximal ATP synthetic capacity, MVO2 and mechanical performance. Whether subsequent steps in the ATP synthetic process are also limiting is unclear. Whether maximal MVO2 and mechanical performance in the abnormal heart are also limited by ATP synthetic capacity is unknown. The objectives of the current proposal are to: 1) continue development of new techniques applicable to in vivo MRI and MRS studies; 2) use these new techniques to define further the rate limiting step in the ATP synthesis process that ultimately restricts maximal MVO2 in the normal heart; and 3) to use these same methods to examine the functional and bioenergetic responses of the remodeled (post-infarction) myocardium to basal and maximal workstates and to determine whether ATP synthetic capacity ultimately restricts maximal MVO2 in the remodeled heart. The applicant will examine the in vivo transmural responses of myocardial high energy phosphates, ventricular performance, blood flow, myocyte deoxymyoglobin saturation and MVO2 under baseline and maximal workstate conditions in normal pigs and pigs with post-infarction remodeling. These data will be correlated with myocyte morphometric data. Conventional physiological methods and magnetic resonance imaging and (spatially localized) magnetic resonance spectroscopy techniques will be employed; the latter provide a unique opportunity to study transmurally heterogeneous metabolic responses of normal and remodeled myocardium.