Cardioprotective effects of KB-R7943, a novel inhibitor of Na⁺/Ca²⁺ exchanger, on stunned myocardium in anesthetized dogs

Abstract

Purpose

The present study was carried out to determine the cardioprotective effects of KB-R7943 (KBR), a selective inhibitor of the reverse mode of Na⁺/Ca²⁺ exchanger (NCX), on stunned myocardium in anesthetized dogs.

Methods

The dogs were allocated to one of three groups (n = 7 for each group), and received drug vehicle (group C), low-dose KBR (5 mg·kg⁻¹ i.v.) (group L) or high-dose KBR (10 mg·kg⁻¹ i.v.) (group H) at 15 min before left anterior descending coronary artery (LAD) occlusion. Stunned myocardium was produced by 15-min occlusion of LAD and 90-min reperfusion in all dogs. Regional myocardial contractility was evaluated with segment shortening (%SS).

Results

Recovery of %SS at 90 min after reperfusion was significantly improved in group H (70.8% ± 3.9% of baseline), whereas the recovery was poor in groups C and L (34.3% ± 2.8% and 36.4% ± 5.4% of baseline, respectively). Regional myocardial blood flow showed no significant difference among groups. KBR had no effect on coronary or systemic hemodynamics.

Conclusion

The results show that preischemic administration of high-dose KBR markedly improves myocardial contractile dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR protects myocardium against the ischemia-reperfusion injury in vivo.