A cardioprotective agent of a novel calpain inhibitor, SNJ-1945, exerts beta1 actions on left ventricular mechanical work and energetics.

We have previously shown that a newly developed calpain inhibitor, SNJ-1945 (SNJ), with good aqueous solubility prevents the heart from KCl arrest-reperfusion injury associated with the impairment of total Ca(2+) handling by inhibiting the proteolysis of alpha-fodrin as a cardioplegia. The aim of the present study was to investigate certain actions of this calpain inhibitor, SNJ, on left ventricular (LV) mechanical work and energetics in cross-circulated excised rat hearts undergoing blood perfusion with 40 microM SNJ. Mean end-systolic pressure at midrange LV volume and systolic pressure-volume area (PVA) at mLVV (a total mechanical energy/beat) were significantly increased by SNJ perfusion (P < 0.01). Mean myocardial oxygen consumption per beat (Vo(2)) intercepts (Vo(2) for the total Ca(2+) handling in excitation-contraction coupling and basal metabolism) of Vo(2)-PVA linear relations were significantly increased (P < 0.01) with unchanged mean slopes of Vo(2)-PVA linear relations. Pretreatment with the selective beta(1)-blocker landiolol (10 microM) blocked these effects of SNJ perfusion. There were no significant differences in mean basal metabolic oxygen consumption among normal, 40 microM SNJ, and 10 microM landiolol + 40 microM SNJ groups. Our results indicate that water-soluble SNJ exerted positive actions on mechanical work and energetics mediated via beta(1)-adrenergic receptors associated with the enhancement of total Ca(2+) handling in excitation-contraction coupling and with unchanged contractile efficiency. In clinical settings, this pharmacological action of SNJ is beneficial as an additive agent for cardioplegia.