Diabetes rapidly induces contractile dysfunctions in isolated
ventricular myocytes.
Ren, Jun, and Amy J. Davidoff.
Program in Molecular and Cellular Cardiology, Department of
Internal Medicine, Wayne State University School of Medicine,
Detroit, MI 48201
APStracts 3:0295H, 1996.
To determine whether diabetes-induced cardiac dysfunction is due to
contractile dysfunction at the single cell level, mechanical
properties and Ca2+ transients were evaluated in ventricular myocytes
isolated from diabetic rats. Rats were made diabetic by injection
with streptozotocin, and sacrificed either 4-6 days or 8 weeks after
treatment. Shortening/relengthening (twitch) properties were
evaluated in isolated myocytes with a high resolution (120 Hz) video
-based edge detection system during electrical stimulation between
0.1-5 Hz. A separate cohort of myocytes were loaded with fura-2 to
assess intracellular Ca2+ transients. Long-term (8 weeks) but not
short-term (4-6 days) diabetes depressed peak twitch amplitude.
Diabetes markedly prolonged both contraction and relaxation phases
from both diabetic models. Additionally, 35% of the long-term
diabetic myocytes could not pace at 5 Hz, and 48% of the short-term
diabetic myocytes developed a hypercontracture at that frequency.
Intracellular Ca2+ measurements showed slower Ca2+ transient decays
in myocytes from short-term diabetic rats. These data demonstrate
that contractile dysfunction seen in the diabetic heart is due, in
part, to abnormalities of the myocyte. Furthermore, these
abnormalities are present after only 4-6 days of diabetes, suggesting
a rapid alteration in the processes regulating myocyte shortening and
relengthening, which likely includes impaired Ca2+ sequestration or
extrusion.
Received 24 June 1996; accepted in final form 3 April 1996.
APS Manuscript Number H306-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996