Abstract
BACKGROUND: Heart failure (HF) frequently follows the occurrence of
myocardial infarction (MI). Questions about how HF develops and
what cellular defects contribute to this dysfunction led to this
study. Methods and Results-- MI was induced in rats by coronary
artery ligation. Clinical examination of the post-MI (PMI) surviving
animals indicated that they were in overt HF by all measures. Cellular
examination of the cardiomyocytes by patch-clamp and confocal Ca$^2+$(i)
imaging methods indicated that cellular function was significantly
compromised. At the single-cell level, Ca$^2+$(i) transient
amplitudes were reduced and contractions were decreased and slowed,
although Ca$^2+$ current (I(Ca)) remained unchanged. The excitation-contraction
coupling (ECC) gain function measured as DeltaCa$^2+$(i)/I(Ca)
was significantly decreased. Ouabain, a cardiotonic steroid that
blocks the Na$^+$,K$^+$-ATPase and activates Ca$^2+$
entry via cardiac Na$^+$ channels, largely alleviated this defect.
CONCLUSIONS: After MI, I(Ca) becomes less able to trigger release
of Ca$^2+$ from the sarcoplasmic reticulum. This failure of ECC
is a major factor contributing to the development of contractile
dysfunction and HF in PMI animals. The improved ECC gain, enhanced
Ca$^2+$ entry, and augmented Ca$^2+$ signaling due to cardiotonic
steroids contribute to the beneficial effects of these agents.
- 11489776
- agents,
- animals,
- calcium
- calcium,
- cardiotonic
- cell
- channels,
- congestive,
- contraction,
- failure,
- gov't,
- heart
- hypertrophy,
- infarction,
- male,
- membrane
- myocardial
- myocardium,
- non-u.s.
- ouabain,
- p.h.s.,
- potentials,
- rate,
- rats,
- research
- reticulum,
- sarcoplasmic
- signaling,
- size,
- support,
- survival
- tetrodotoxin,
- u.s.
- wistar,
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