Decrease in ischemic tolerance with aging in isolated perfused Fischer 344 rat hearts: Relation to increases in intracellular Na+ after ischemia

Masato Tani, Yukako Suganuma, Hiroshi Hasegawa, Ken Shinmura, Yoshinori Ebihara, Yoko Hayashi, Xiao Dong Guo, Michiyo Takayama

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54 Citations (Scopus)


While the ischemic tolerance of the myocardium has been reported to decrease with senescence, it is not known when and how this occurs. Our objectives were to determine whether the tolerance to myocardial ischemia in rats decreased before the onset of senescence and whether an increase in myocardial ionic imbalance was associated with an enhanced myocardial injury with aging. Hearts were isolated from Fischer 344 rats categorized as young (12 weeks old), mature adult (24 weeks), middle-aged (50 weeks) or senescent (100 weeks). Hearts were perfused isovolumically by the Langendorff procedure and subjected to 25 min of global ischemia followed by 30 min of reperfusion. In the 50- and 100-week-old rats, the recovery of ventricular function and high-energy phosphate levels was lower and there was increased incidence of ventricular fibrillation after 25 min of global ischemia followed by reperfusion. The release of creatine kinase and lactate dehydrogenase during reperfusion was greater in the 50-and 100-week-old rats than in the 12- and 24-week-old rats, indicating the irreversible myocardial damage due to ischemia-reperfusion increased by middle-age. Intracellular levels of Na+ and K+ before ischemia were higher in the 50- or 100-week-old rats than in the 12-week-old rats. The increase in intracellular Na+ at end of ischemia was greater in the older (50-week-old, 215% of the pre-ischemic value; 100-week-old, 232% of the pre-ischemic value) than in the younger rats (12-week-old, 158% of the pre-ischemic value). Results indicated that the rat heart becomes more vulnerable to ischemia in middle-age. This decrease in ischemic tolerance may be caused by an acceleration of myocardial ionic imbalance with aging.

Original languageEnglish
Pages (from-to)3081-3089
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Issue number11
Publication statusPublished - 1997 Nov


  • Creatine kinase
  • Intracellular Na
  • Ionic imbalance
  • Reperfusion injury
  • Reperfusion-induced arrhythmia
  • Ventricular function

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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