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Lactic acidosis: an experimental model.

A I Arieff, A Kerian

    Metabolism: Clinical and Experimental
    |March 1, 1976
    PubMed
    Summary

    Diabetic rabbits developed spontaneous lactic acidosis after beta-hydroxybutyric acid and sodium bicarbonate infusions. This model shows altered NAD/NADH ratios and increased lactate, highlighting metabolic disturbances in diabetes.

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    Area of Science:

    • Biochemistry
    • Physiology
    • Endocrinology

    Background:

    • Diabetic ketoacidosis is a serious complication of diabetes mellitus.
    • Lactic acidosis can occur in diabetes, but its spontaneous development is not fully understood.
    • Alloxan-induced diabetes in rabbits provides a model for studying metabolic derangements.

    Purpose of the Study:

    • To develop a reproducible model of spontaneous lactic acidosis in diabetic rabbits.
    • To investigate the metabolic changes associated with induced lactic acidosis in a diabetic model.
    • To compare the response of diabetic versus normal rabbits to the induction protocol.

    Main Methods:

    • Alloxan was used to induce diabetes in rabbits.
    • Intravenous infusion of beta-hydroxybutyric acid and sodium bicarbonate was administered.
    • Arterial blood gases, lactate/pyruvate ratio, and NAD/NADH ratio were measured.
    • Cardiorespiratory parameters were monitored.

    Main Results:

    • Diabetic rabbits developed significant lactic acidosis, with elevated lactate/pyruvate ratios and decreased arterial pH.
    • The NAD/NADH ratio was significantly lower in rabbits with lactic acidosis compared to normal controls.
    • Normal rabbits did not develop lactic acidosis under the same experimental conditions.
    • Continued sodium bicarbonate infusion in diabetic rabbits led to increased blood lactate and cardiorespiratory arrest in 36% of animals.

    Conclusions:

    • A model for spontaneous lactic acidosis was successfully established in alloxan-induced diabetic rabbits.
    • The model demonstrates altered redox state (NAD/NADH ratio) contributing to lactic acidosis in diabetes.
    • This experimental model is valuable for studying the pathophysiology and potential treatments of lactic acidosis in diabetes.

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