Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts

Masato Tani, Yukako Suganuma, Hiroshi Hasegawa, Ken Shinmura, Yoko Hayashi, Xiao Dong Guo, Yoshiro Nakamura

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Background: Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats. Methods and Results: The hearts of young adult rats 112 weeks old: group Y, n=44) and middle-aged rats (50 weeks old: group M, n=44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 2 (group Y, n=22) or 15 (group M, n=22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40,5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14. 1; creatine phosphate, 17.0 to 23.1 μmol/g dry wt) and reduced left ventricular end- diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 μmol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion induced ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M. Conclusions: These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.

Original languageEnglish
Pages (from-to)2559-2566
Number of pages8
JournalCirculation
Volume95
Issue number11
Publication statusPublished - 1997

Fingerprint

Ischemic Preconditioning
Ventricular Pressure
Ischemia
Reperfusion
Adenosine Triphosphate
Sarcoplasmic Reticulum
Young Adult
Myocardium
Ryanodine
Phosphocreatine
Ventricular Fibrillation
Creatine Kinase
Phosphates
Blood Pressure
Incidence

Keywords

  • aging
  • creatine kinase
  • ischemia
  • reperfusion
  • sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Tani, M., Suganuma, Y., Hasegawa, H., Shinmura, K., Hayashi, Y., Guo, X. D., & Nakamura, Y. (1997). Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts. Circulation, 95(11), 2559-2566.

Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts. / Tani, Masato; Suganuma, Yukako; Hasegawa, Hiroshi; Shinmura, Ken; Hayashi, Yoko; Guo, Xiao Dong; Nakamura, Yoshiro.

In: Circulation, Vol. 95, No. 11, 1997, p. 2559-2566.

Research output: Contribution to journalArticle

Tani, M, Suganuma, Y, Hasegawa, H, Shinmura, K, Hayashi, Y, Guo, XD & Nakamura, Y 1997, 'Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts', Circulation, vol. 95, no. 11, pp. 2559-2566.
Tani M, Suganuma Y, Hasegawa H, Shinmura K, Hayashi Y, Guo XD et al. Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts. Circulation. 1997;95(11):2559-2566.
Tani, Masato ; Suganuma, Yukako ; Hasegawa, Hiroshi ; Shinmura, Ken ; Hayashi, Yoko ; Guo, Xiao Dong ; Nakamura, Yoshiro. / Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts. In: Circulation. 1997 ; Vol. 95, No. 11. pp. 2559-2566.
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T1 - Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts

AU - Tani, Masato

AU - Suganuma, Yukako

AU - Hasegawa, Hiroshi

AU - Shinmura, Ken

AU - Hayashi, Yoko

AU - Guo, Xiao Dong

AU - Nakamura, Yoshiro

PY - 1997

Y1 - 1997

N2 - Background: Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats. Methods and Results: The hearts of young adult rats 112 weeks old: group Y, n=44) and middle-aged rats (50 weeks old: group M, n=44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 2 (group Y, n=22) or 15 (group M, n=22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40,5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14. 1; creatine phosphate, 17.0 to 23.1 μmol/g dry wt) and reduced left ventricular end- diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 μmol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion induced ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M. Conclusions: These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.

AB - Background: Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats. Methods and Results: The hearts of young adult rats 112 weeks old: group Y, n=44) and middle-aged rats (50 weeks old: group M, n=44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 2 (group Y, n=22) or 15 (group M, n=22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40,5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14. 1; creatine phosphate, 17.0 to 23.1 μmol/g dry wt) and reduced left ventricular end- diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 μmol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion induced ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M. Conclusions: These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.

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KW - creatine kinase

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KW - sarcoplasmic reticulum

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