Complement-mediated
neutrophil activation has been hypothesized to be an important mechanism of
reperfusion injury. It has been proposed that
C1 esterase inhibitor (C1 INH) may prevent the
complement-dependent activation of
polymorphonuclear leukocytes (PMNs) that occurs within postischemic
myocardium. Therefore, The effect of C1 INH was examined in
neutrophil dependent isolated perfused
rat heart model of
ischemia (I) (20 min) and
reperfusion (R) (45 min).
Administration of C1 INH (5 mg/Kg) to I/R
hearts in the presence of PMNs (100 X 106) and homologous
plasma improved coronary flow and preserved cardiac contractile function (p<0.001) in comparison to those I/R
hearts receiving only vehicle. In addition, C1 INH significantly (p<0.001) reduced PMN accumulation in the ischemic
myocardium as evidenced by an attenuation in
myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective
cardioprotective agent inhibits
leukocyte-endothelial interaction and preserves cardiac contractile function and coronary
perfusion following
myocardial ischemia and
reperfusion.