Cardioprotective effects of KB-R7943: a novel inhibitor of the reverse mode of Na+/Ca2+ exchanger

Am J Physiol. 1999 Jun;276(6):H1868-76. doi: 10.1152/ajpheart.1999.276.6.H1868.


The novel inhibitor of the reverse mode of the Na+/Ca2+ exchanger (NCE) KB-R7943 (KB) was tested in isolated rat cardiomyocytes exposed to 80 min of simulated ischemia [substrate-free anoxia, extracellular pH (pHo) of 6.4] and 15 min of reoxygenation (pHo 7.4). At pHo 6.4, 20 micromol/l KB was required for complete inhibition of the reverse mode of NCE. Treatment with 20 micromol/l KB only during anoxia did not influence the onset of rigor contracture and intracellular pH (pHi) (monitored with 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein) but significantly reduced the cytosolic accumulation of Ca2+ (monitored with fura 2) and Na+ (monitored with sodium-binding benzofuran isophthalate). During reoxygenation, cardiomyocytes developed hypercontracture. This was significantly reduced by anoxic KB treatment. To investigate this protection against reoxygenation-induced injury in the whole heart, we exposed Langendorff-perfused rat hearts to 110 min of anoxia (pHo 6.4) and 50 min of reoxygenation (pHo 7.4). Application of 20 micromol/l KB during anoxia significantly reduced the reoxygenation-induced enzyme release. We conclude that KB offers significant protection of cardiomyocytes against Ca2+ and Na+ overload during anoxia and hypercontracture or enzyme release on reoxygenation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Heart / drug effects*
  • Hydrogen-Ion Concentration
  • Hypoxia / metabolism
  • In Vitro Techniques
  • Magnesium / metabolism
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Ischemia / physiopathology
  • Myocardial Reperfusion Injury / prevention & control
  • Osmolar Concentration
  • Oxygen / adverse effects
  • Oxygen / pharmacology
  • Rats
  • Rats, Wistar
  • Sodium-Calcium Exchanger / antagonists & inhibitors*
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology
  • Time Factors


  • 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
  • Sodium-Calcium Exchanger
  • Thiourea
  • Magnesium
  • Oxygen
  • Calcium