Effects of Ischemic Preconditioning on Na+-Ca2+ Exchanger Activity and Ion Regulation in Isolated Perfused Rat Hearts

  • Shingo Seki
  • Hiroyuki Okumura
  • Takehiko Izumi
  • Fumiko Okazaki
  • Satoshi Takeda
  • Masayuki Taniguchi
  • Ikuo Taniguchi
  • Seibu Mochizuki
Part of the Progress in Experimental Cardiology book series (PREC, volume 1)


We investigated the effects of ischemic preconditioning (IP) on the incidence of reperfusion-induced ventricular fibrillation (VF), intracellular ion regulation, and Na+-Ca2+ exchanger activity using isolated perfused rat hearts. The hearts perfused in a working-heart mode were exposed to sustained global ischemia for 15 minutes and were reperfused for 20 minutes. For preconditioning, the hearts were exposed to two short periods (3 or 5 minutes) of ischemia and repehsion prior to induction of sustained ischemia. The incidence of VF decreased from 90% in the control hearts to 20% in the preconditioned hearts (p < 0.05). Treatment with an Na+-Ca2+ exchanger blocker, Ni2+ (0.5 μM, reduced the antianhythmic effect of IP. Thus, 70% of the preconditioned hearts treated with Ni2+ developed VF on reperfusion. To investigate the effect of IP on changes in intracellular ion levels, rat hearts perfused in Langendorff’s mode were exposed to low-flow ischemia for 15 minutes and were reperfused for 15 minutes. Intracellular pH (pHi) and Ca2+ concentrations ([Ca2+]i) were measured ratiometrically using the fluorescent ion indicators 2′,7′-bis(2-carboxylethyl)-5(6)-carboxyfluorescein (BCECF) or fura-2 with the simultaneous measurement of left ventricular pressure. IP limited the development of intracellular acidosis and prevented the rise in diastolic [Ca2+]i during sustained ischemia. Ni2+ treatment reversed this effect of IP on diastolic [Ca2+]i. During exposure to an Na+ free extracellular medium, which reversed the Na+-Ca2+ exchanger mode, IP significantly suppressed the peak amplitude (65.2% ± 7.8% of control, p < 0.005) and prolonged the time to peak (16.7 ± 0.9 seconds vs. 12.8 ± 1.5 seconds, p < 0.05) of the diastolic [Ca2+]i increase. Results indicated that the Na+-Ca2+ exchanger may be important in ion regulation during IP.


Ventricular Fibrillation Ischemic Precondition Left Ventricular Pressure Control Heart Forward Mode 
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Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Shingo Seki
    • 1
  • Hiroyuki Okumura
    • 1
  • Takehiko Izumi
    • 1
  • Fumiko Okazaki
    • 1
  • Satoshi Takeda
    • 1
  • Masayuki Taniguchi
    • 1
  • Ikuo Taniguchi
    • 1
  • Seibu Mochizuki
    • 1
  1. 1.Jikei University School of MedicineJapan

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