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Related Experiment Videos

Reduced cardiac functional reserve in apolipoprotein E knockout mice.

Jon Vincelette1, Baby Martin-McNulty, Ronald Vergona

  • 1Department of Pharmacology, Berlex Biosciences, Richmond, California.

Translational Research : the Journal of Laboratory and Clinical Medicine
|August 5, 2006
PubMed
Summary

Apolipoprotein E knockout mice show higher resting cardiac function but reduced cardiac reserve under dobutamine stress, indicating impaired response due to atherosclerosis.

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Area of Science:

  • Cardiovascular Research
  • Mouse Models of Atherosclerosis
  • Pharmacological Stress Testing

Background:

  • Apolipoprotein E knockout (apoE-KO) mice exhibit higher resting aortic flow velocity compared to wildtype (WT) controls.
  • Understanding the cardiac functional reserve in apoE-KO mice is crucial for modeling atherosclerosis-related cardiovascular disease.

Purpose of the Study:

  • To investigate the cardiac functional reserve in apoE-KO mice under pharmacological stress.
  • To compare the response to dobutamine stress between apoE-KO and WT mice.

Main Methods:

  • Noninvasive Doppler ultrasound was used to measure cardiac function in 16-month-old male apoE-KO and WT mice.
  • Mice received intraperitoneal injections of dobutamine at varying doses (1, 3, 10 µg/g) under light anesthesia.

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  • Cardiac function parameters were assessed at baseline and at multiple time points post-injection.

    • Main Results:

    • ApoE-KO mice displayed significantly higher baseline aortic flow velocities and left ventricular contractility than WT mice.
    • Dobutamine stress dose-dependently increased cardiac function in both groups, but the response was attenuated in apoE-KO mice.
    • The dose-response curve for dobutamine was shifted to the right in apoE-KO mice, indicating reduced functional reserve.

    Conclusions:

    • Despite enhanced resting cardiac function, apoE-KO mice exhibit a significantly reduced cardiac functional reserve in response to dobutamine stress.
    • This diminished reserve is likely attributed to coronary atherosclerosis and endothelial dysfunction, limiting myocardial blood supply.
    • These findings highlight impaired cardiac stress response in apoE-KO mice, relevant for atherosclerosis research.