| Abstrakt: |
Reducing intracellular Na+-accumulation during ischemia exerts cardioprotective effects in reperfusion in a variety of models. Since slowly-inactivating Na+-channels may contribute to Na+-influx in ischemia, we investigated whether the ischemia-protective properties of R 56865, an inhibitor of slowly inactivating Na+-channels, are mediated by inhibition of the ischemic Na+-overload. Monitoring intracellular Na+ (Na+i) by 23Na-NMR-spectroscopy revealed a continuous rise of Na+i during ischemia in the isolated perfused guinea pig heart. Within 30 and 60 min of ischemia, respectively, Na+i had risen 2.6±0.2- and 4.4±0.2-fold compared to baseline (n=6). R 56865 (1 μM) did not influence the time course of the Na+i-accumulation at any point of the ischemic period. R 56865, however, showed marked cardioprotective properties: in the reperfusion period the agent markedly improved the restoration of left ventricular developed pressure (29.1±6.8 mm Hg vs. 2.4±2.0 mm Hg), ATP (2.8±0.3 mM vs. 1.7±0.6 mM) and phosphocreatine (10.9±2.2 mM vs. 6.8±1.1 mM), furthermore contracture development was reduced. The present study strongly suggests slowly-inactivating Na+-channels being at best a minor port of Na+-entry in the ischemic guinea pig heart. It clearly demonstrates that the potent cardioprotective properties of R 56865 are unrelated to intracellular sodium homeostasis. [ABSTRACT FROM AUTHOR] |
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