Circulation, Vol 77, 685-695, Copyright © 1988 by American Heart Association
M Kitakaze, HF Weisman and E Marban
Although a number of lines of evidence hint that an elevation of
intracellular calcium leads to myocardial injury, the cellular consequences
of transient Ca overload remain unclear. To determine the contractile,
histologic, and metabolic sequelae of transient Ca overload, we measured
developed pressure (DP) in isovolumetric Langendorff-perfused ferret hearts
at 37 degrees C before and 20 min after three 5 min periods of perfusion
with a 10 mM [Ca]o, 1 mM [Mg]o solution (high-Ca group, n = 8) without
ischemia, and in control hearts (n = 5) exposed transiently to the same
total divalent cation concentration without a change in [Ca]o (9 mM [Mg]o,
2mM [Ca]o). DP, measured at various [Ca]o (0.5 to 5 mM), was depressed in
the high-Ca group relative to control (p less than .001). Representative
hearts from the control group were histologically normal, whereas hearts
from the high-Ca group exhibited rare foci of predominantly "reversible"
injury (mitochondrial swelling, glycogen deposition, and clumping of
nuclear chromatin). Maximal Ca++-activated pressure (MCAP), measured from
tetani after exposure to ryanodine, was also decreased in the high- Ca
group (230 +/- 4 vs 262 +/- 6 mm Hg, p less than .001). Cao sensitivity,
determined by normalization of the DP-[Ca]o relationship to the
corresponding MCAP, was shifted to higher [Ca]o in the high-Ca group.
Phosphorus nuclear magnetic resonance spectra were obtained in four high-Ca
hearts. [ATP] declined by 30% to 40% after exposure to high [Ca]o, but
inorganic phosphate, phosphocreatine, and pH remained unchanged. These
results indicate that transient exposure to high [Ca]o without ischemia
leaves behind distinctive contractile, metabolic, and histologic sequelae.
The possible implications for the pathogenesis of postischemic contractile
dysfunction are discussed.
ARTICLES
Contractile dysfunction and ATP depletion after transient calcium overload in perfused ferret hearts
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
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