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Related Experiment Videos

Peroxynitrite impairs cardiac contractile function by decreasing cardiac efficiency

R Schulz1, K L Dodge, G D Lopaschuk

  • 1Department of Pediatrics, University of Alberta, Edmonton, Canada. richard.schulz@ualberta.ca

The American Journal of Physiology
|March 1, 1997
PubMed
Summary
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High concentrations of peroxynitrite (ONOO-) impair heart function and efficiency by disrupting energy metabolism, unlike the NO donor SNAP. This suggests ONOO- negatively impacts cardiac performance during disease.

Area of Science:

  • Biochemistry
  • Cardiovascular Physiology
  • Cellular Metabolism

Background:

  • Peroxynitrite (ONOO-) is implicated in cellular dysfunction and cardiac mechanical depression during pathophysiological conditions.
  • Understanding the specific effects of ONOO- on cardiac energy metabolism and function is crucial for elucidating its role in heart disease.

Purpose of the Study:

  • To investigate the impact of peroxynitrite (ONOO-) on cardiac function and energy metabolism in isolated working rat hearts.
  • To compare the effects of ONOO- with those of a nitric oxide (NO) donor, S-nitroso-DL-acetylpenicillamine (SNAP).

Main Methods:

  • Isolated working rat hearts were perfused under aerobic conditions.
  • Hearts were treated with either ONOO- (4 or 40 microM), SNAP (40 microM), or vehicle controls over a 60-minute infusion period.

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  • Cardiac function (work), oxygen consumption, coronary flow, and substrate oxidation (glucose, pyruvate) were measured.

    • Main Results:

    • High-dose ONOO- (40 microM) significantly reduced cardiac work and efficiency with a delayed onset, without altering oxygen consumption.
    • ONOO- enhanced glycolysis and glucose oxidation but did not affect pyruvate oxidation.
    • SNAP and vehicle treatments did not alter cardiac function, oxygen consumption, or metabolic parameters.

    Conclusions:

    • Peroxynitrite (ONOO-) depresses cardiac mechanical efficiency, potentially by uncoupling ATP production from mechanical work.
    • The observed effects of ONOO- on cardiac efficiency are distinct from those of the NO donor SNAP.
    • ONOO- appears to interfere with specific pathways of cardiac energy metabolism, contributing to functional decline.