抄録
We hypothesized that calpain inhibitor-1 (CI) protected left ventricular (LV) function from ischemic-reperfusion (IR) injury by inhibiting the proteolysis of α-fodrin. To test this hypothesis, we investigated the effect of CI on LV mechanical work and energetics in the cross-circulated rat hearts that underwent 15-min global ischemia and 60-min reperfusion (n=9). After IR with CI, mean end-systolic pressure at midrange LV volume (ESPmLVV) and systolic pressure-volume area (PVA) at mLVV (PVAmLVV) were hardly changed, although they were significantly (P<0.01) decreased after IR without CI. Mean myocardial oxygen consumption per beat (VO2) intercepts of VO2-PVA linear relations were also unchanged after IR with CI, although they were significantly (P<0.01) decreased after IR without CI. VO2 for the Ca2+ handling was significantly higher than pre IR from 10 to 15 min after IR. CI did not block this energy-wasting process. There were no significant differences in O2 costs of LV PVA and contractility among the hearts in control (or normal), post IR and post IR with CI. Western blotting of α-fodrin and the immunostaining of 150-kD products of α-fodrin confirmed that CI almost completely protected proteolysis of α-fodrin. Our results indicate that CI prevents the heart from IR injury associated with the impairment of total calcium handling by directly inhibiting the proteolysis of α-fodrin. [Jpn J Physiol 55 Suppl:S92 (2005)]
