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Decrease in ischemic tolerance with aging in isolated perfused Fischer 344 rat hearts: relation to increases in

M Tani1, Y Suganuma, H Hasegawa

  • 1Department of Geriatric Medicine, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160, Japan.

Journal of Molecular and Cellular Cardiology
|February 28, 1998
PubMed
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The aging rat heart shows reduced tolerance to ischemia and reperfusion injury, beginning in middle age. This vulnerability is linked to an increased myocardial ionic imbalance, particularly sodium and potassium levels, with advancing age.

Area of Science:

  • Cardiovascular Physiology
  • Gerontology
  • Biochemistry

Background:

  • Myocardial tolerance to ischemia decreases with senescence.
  • The precise timing and mechanisms of this age-related decline remain unclear.
  • Investigating early-life changes in myocardial ionic balance is crucial for understanding aging effects.

Purpose of the Study:

  • To determine if myocardial ischemic tolerance declines before senescence in rats.
  • To investigate the association between myocardial ionic imbalance and enhanced injury with aging.
  • To identify the age at which hearts become more vulnerable to ischemia-reperfusion.

Main Methods:

  • Isolated hearts from Fischer 344 rats of varying ages (young, mature adult, middle-aged, senescent) were used.

Related Experiment Videos

  • Hearts underwent 25 minutes of global ischemia followed by 30 minutes of reperfusion using the Langendorff procedure.
  • Ventricular function, high-energy phosphate levels, enzyme release (creatine kinase, lactate dehydrogenase), and intracellular ion concentrations (Na+, K+) were measured.

    • Main Results:

    • Middle-aged (50 weeks) and senescent (100 weeks) rats exhibited reduced recovery of ventricular function and lower high-energy phosphate levels post-ischemia/reperfusion.
    • Increased incidence of ventricular fibrillation and greater release of creatine kinase and lactate dehydrogenase were observed in older rats, indicating enhanced irreversible myocardial damage.
    • Older rats showed higher pre-ischemic intracellular Na+ and K+ levels, with a more pronounced increase in intracellular Na+ during ischemia compared to younger rats.

    Conclusions:

    • The rat heart's tolerance to ischemia decreases significantly by middle age, preceding senescence.
    • An accelerated myocardial ionic imbalance, characterized by elevated intracellular Na+ and K+, is associated with this heightened vulnerability to ischemia-reperfusion injury.
    • These findings suggest that interventions targeting ionic balance may be beneficial in mitigating age-related cardiac dysfunction.