Project: Research project

Project Details


DESCRIPTION: Contractile function in ventricles surviving substantial
myocardial infarction (MI) is improved by exercise training. The current
proposal focuses on cellular mechanisms by which exercise training effects
an improvement in contractile function. Our data demonstrate both altered
(Ca2+)i dynamics in MI myocytes and exercise training enhance both Ca2+
influx and efflux pathways in normal myocytes. We hypothesize that exercise
training can: (i) restore normal (Ca2+)i dynamics and contractile function
to MI myocytes; and (ii) reverse MI-induced pathology in subcellular Ca2+
regulatory pathways. To test our hypothesis, male Sprague-Dawley rats will
undergo LV infarct, allowed to recover for 3 weeks, studied with Echo to
match LV infarct size (35-50 percent), and then start a 6-week high
intensity sprint training (HIST). Single myocytes from the septum (remote
from scar) and LV free wall (close to the scar) will be isolated from
sedentary (Sed, MISed) and exercised-trained (HIST, MIHIST) rats. (Ca2+)i
dynamics, contractile function and myosin heavy chain isoform distribution
will be simultaneously measured with microfluorimetry, video edge detector
and single cell SDS-PAGE. Ca2+ influx via L-type Ca2+ channel and Na+-Ca2+
exchange will be measured with whole-cell patch clamp. Releasable SR Ca2+
content will be assayed with caffeine induced SR Ca2+ release and rapid
cooling contractures. SR Ca2+ uptake and SR Ca2+ leak will be examined.
Finally, manipulations of Ca2+ fluxes will be undertaken to test the
hypothesis that altered (Ca2+)i dynamics is causally related to depressed
contraction function in MI myocytes and that HIST's beneficial effects on
myocyte contractions are mediated via modulation of Ca2+ homeostatic
Effective start/end date7/1/008/31/00


  • National Heart, Lung, and Blood Institute: $416.00

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