INHIBITION OF ELASTASE IMPROVES MYOCARDIAL-FUNCTION AFTER REPETITIVE ISCHEMIA AND MYOCARDIAL-INFARCTION IN THE RAT-HEART

We investigated the potential of inhibition of elastase, a granulocyte -derived proteolytic enzyme, in ameliorating the effects of myocardial stunning caused by repetitive ischaemia (RI) and myocardial infarctio n (MI) for the first time in an in situ, perfused, rat heart model. Th e effects of the elastase-inhibitors Elafin (EL, 10 mg/kg/h) and ICI 2 00,880 (ICI,5 mg/kg/h) on myocardial blood flow (MBF, H-2 clearance), regional myocardial function (FT, pulsed doppler) and neutrophil extra vasation (myocardial myeloperoxidase activity, MPO) were investigated in RI (5x10 min ligature of the anterior descending ramus (LAD), 5x20 min reperfusion) and MI (50 min LAD ligature, 60 min reperfusion). Und er control conditions, MBF and FT were significantly reduced and MPO w as significantly increased after RI (n=8) and MI (n=8) in the ischaemi c area compared with baseline. Pretreatment with EL (n=7) or ICI (n=7) did not improve MBF significantly and did not influence the successiv e attenuation of peak values of reactive hyperaemia, However, both EL and ICI significantly improved FT and significantly reduced MPO after RI and MI compared with control conditions. Additionally, both the are a at risk and MI size were reduced significantly by both inhibitors. T hese results demonstrate that elastase inhibitors significantly improv e the reduction of FT both in myocardial stunning and in myocardial in farction in the rat without significant improvement of MBF. It is conc luded that elastase inhibitors exert a cardioprotective effect against reperfusion injury, probably by inhibition of leukocyte extravasation as indicated by the decrease in MPO activity.