Vol. 275, Issue 5, H1834-H1844, November 1998
A load-independent in vivo model for evaluating therapeutic
interventions in injured myocardium
Cleveland W.
Lewis1,
B. Zane
Atkins1,
Kelley A.
Hutcheson2,
Christian T.
Gillen3,
Mary C.
Reedy4,
Donald D.
Glower1,3, and
Doris A.
Taylor1,2,3
Departments of 2 Medicine,
1 Surgery,
3 Biomedical Engineering, and
4 Cell Biology, Duke
University Medical Center, Durham, North Carolina 27710
Although
cardiomyocyte damage is normally irreversible, gene therapy and somatic
cell transfer offer potential for improving function in damaged regions
of the heart. However, in ischemic models of injury, variability in
depth, size, and location of damage compromises statistical evaluation
of in vivo function. We have adapted cryoablation to create a
reproducible, posterior, transmural lesion within rabbit myocardium in
which small changes in function are measurable in vivo. Before and at 2 and 6 wk postinjury, in vivo left ventricular intracavitary pressure
and myocardial segment length were measured. Regional indexes of
performance, segmental stroke work (SW), and percent systolic
shortening (SS) were significantly decreased
(P < 0.001) postcryoinjury as was the slope (Mw)
of the linear preload recruitable SW relationship between SW and
end-diastolic segment length (P = 0.0001). Decreased SW, SS, and
Mw correlated
with wall thinning, loss of myocytes, presence of fibroblasts, and
transmural scar formation. Reproducible changes in regional myocardial
performance in vivo postcryoinjury suggest that this is a reasonable
model for evaluating novel therapies for cardiovascular disease.
regional cardiac function; contractility; cryoinjury; myocardial
infarction; cellular cardiomyoplasty; Frank-Starling relationship; preload recruitable stroke work; preload recruitable work area
