Project: Research project

    Project Details


    Although much has been learned about systolic function in the fetal sheep,
    little is known about the relaxation and filling phases of the cardiac
    cycle in immature hearts. The purpose of this application is to investigate
    the cellular and functional aspects of diastole in growing lambs. The
    proposed study is based on the hypothesis that the sarcoplasmic reticulum
    becomes increasingly important with-maturity as a regulator of Ca++ uptake
    during relaxation. The Specific Aims of the study are; 1) to determine the
    developmental changes in diastolic properties of the heart in sheep at 120,
    130, 140, 160, 170 days post-conception 2) to determine the effects of
    myocardial hypoxia on in vivo diastolic function at the same
    post-conception ages; 3) to determine the effect of interventricular
    filling pressure gradients associated with in utero ventilation on the
    diastolic properties of the mature fetal left ventricle; 4) to determine
    the relative importance of sarcolemma vs. sarcoplasmic reticulum in the
    uptake of myoplasma Ca++ during relaxation in isolated ventricular
    myocytes; 5) to determine in isolated immature myocytes, the mechanisms
    responsible for alterations in diastolic Ca++ uptake in the presence of
    Na-K Channel antagonists and beta-adrenergic agonists. Aims.1, 2 and 3 will
    be accomplished in chronically prepared lambs with left ventricular minor
    axis dimensions measured with implanted sonomicrometry crystals and
    implanted micromanometer. Pressure-dimension-time relationships will be
    determined mathematically. The relaxation time constant, T, and the passive
    pressure-dimension curve will be used to quantitate diastolic changes. Aims
    4 and 5 will study Ca++ transients in isolated cells using the florescent
    dye indicator, fura-2. This study is designed to: advance our knowledge of
    the basic mechanisms that underlie normal diastolic function in the
    immature heart; determine effects of 3 drugs that are known to affect
    diastolic function in mature myocardium; determine the role of diastolic
    ventricular interaction in determining increased left ventricular stroke
    volume at birth; and correlate cellular events with in vivo functional
    Effective start/end date8/1/897/31/95


    • National Institutes of Health


    • Medicine(all)


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