Calpain inhibitor-1 protects the heart from ischemic-reperfusion injury, linking to no blockade of more energy-consuming processes

Abstract

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 (ESP_mLVV) and systolic pressure-volume area (PVA) at mLVV (PVA_mLVV) 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)]