Reduced threshold for myocardial cell calcium intolerance in the
rat heart with aging.
Hano, Osamu, Konstantin Yu. Bogdanov, Makoto Sakai, Robert G.
Danziger, Harold A. Spurgeon, and Edward G. Lakatta.
Laboratory of Cardiovascular Science, Gerontology Research Center,
National Institute on Aging, National Institutes of Health,
Baltimore, Maryland, 21224, U.S.A. Present Address: The Third
Department of Internal Medicine, Nagasaki University School of
Medicine, Nagasaki, Japan; Institute of Experimental Cardiology,
National Cardiology Research Center, Russian Academy of Medical
Sciences, Moscow, USSR; Tokyo Metropolitan Geriatric Hospital, Tokyo,
Japan; Columbia University, New York, N.Y.
APStracts 2:0224H, 1995.
To determine whether advancing age is accompanied by a reduced Ca2+
tolerance, we measured: Ca2+-dependent diastolic pressure, prolonged
relaxation and systolic functional deterioration, spontaneous
sarcoplasmic reticulum (SR) generated Ca2+ oscillations, detected as
scattered laser light intensity fluctuations (SLIF),
aftercontractions and ventricular fibrillation in isolated,
isovolumic, atrio-ventricular (AV)-blocked intact hearts from 24-26
mo (old) and 6-8 mo male Wistar rats (young). In enzymatically
isolated, single, cardiac myocytes, the likelihood of the occurrence
of spontaneous contractile waves driven by spontaneous SR Ca2+
release was also determined. In response to stepwise increases in
perfusate [Ca2+], Cao, a reduction in the maximum developed pressure
accompanied by an elevation in end-diastolic pressure and a prolonged
contraction duration was observed at lower Cao in old vs young hearts
(p< 0.01 for each parameter). Furthermore, Ca2+-dependent
ventricular fibrillation occurred during pacing in 6 old but in no
young hearts (p< 0.01), aftercontractions were observed in 7 old
versus 1 young heart (p< 0.01), and SLIF increased to a greater
extent in old versus young hearts. In single cardiac myocytes
spontaneous contractile waves occurred more frequently with
increasing age (p< 0.01). These results indicate that aging is
associated with an increased likelihood for the occurrence of SR
generated Ca2+ oscillations and functional abnormalities that result
from these oscillations.
Received 9 January 1995; accepted in final form 8 May 1995.
APS Manuscript Number H15-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.