Endotoxin-challenge is associated with a dramatic increase in PAI-1-expression and a marked inhibition of norepinephrine overflow from isolated hearts. Since autonomic dysfunction is a strong predictor for death in sepsis, targeting this neuroinhibitory effect of PAI-1 might have valuable therapeutic potential.

Aims. Reperfusion after myocardial ischaemia is associated with a distinct ischaemia/reperfusion injury. Since ACE-inhibition, beyond its influence on cardiac angiotensin II formation and kinin metabolism, has been shown to be cardioprotective by decreasing leucocyte adhesion and endothelin-1 (ET-1) release, we investigated the effects of intracoronary (i.c.) enalaprilat during primary angioplasty in acute myocardial infarction.Methods and results. Twenty-two patients were randomized to receive i.c. enalaprilat (50 mu g) or placebo immediately after reopening of the infarct-related artery (IRA). Plasma concentrations of soluble L-selectin, P-selectin, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), ET-1 and nitric oxide metabolite concentrations (NO(x)) were measured in pulmonary arterial blood. Coronary blood flow was assessed using corrected thrombolysis in myocardial infarction (TIMI) frame counts (CTFC). During reperfusion, there was a significant increase in sL-selectin, sP-selectin and ET-1 in the placebo group, which was greatly diminished by enalaprilat. Levels of sVCAM-1 and sICAM-1 were not affected in either group. CTFC in the placebo group remained higher than normal in both the IRA and nonculprit vessels, whereas myocardial blood flow improved with enalaprilat.Conclusions. Enalaprilat as adjunct to primary angioplasty might be a protective approach to prevent leucocyte adhesion and the release of ET-1, thereby improving coronary blood flow.