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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)

Abstract

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.

Keywords

Ventricular Fibrillation Ischemic Precondition Left Ventricular Pressure Control Heart Forward Mode 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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