Bradykinin accumulation is a potent cardioprotective mechanism underlying
angiotensin-converting enzyme (ACE) inhibition in
ischemia and/or
reperfusion injury. There is, however, concern about treatment with
ACE inhibitors in the very early phase of acute
myocardial infarction (AMI) due to adverse systemic hemodynamic effects. We tested the hypothesis that cardiac
bradykinin metabolism can be influenced by very low doses of intracoronary
ACE inhibitors without harmful systemic effects in patients with AMI. Twenty-two patients with AMI in Killip classes II to III who underwent primary percutaneous transluminal coronary angiography (PTCA) were randomized to intracoronary
enalaprilat (50 microg) or saline, given immediately after reopening of the
infarct-related artery. Hemodynamics and electrocardiograms were monitored continuously and samples for determination of ACE activity,
angiotensin II,
bradykinin,
kininogen, and cardiac marker
proteins were collected from pulmonary arterial and central venous blood.
Enalaprilat had no adverse effects on systemic hemodynamics, but rather stabilized arterial pressure and cardiac rhythm during reperfusion.
Enalaprilat induced a 70% reduction of ACE activity and a significant increase of
bradykinin in pulmonary arterial blood.
Angiotensin II was not significantly affected by
enalaprilat either in pulmonary arterial or in central venous blood.
Myoglobin release was lower and the duration of reperfusion arrhythmias was significantly reduced in the
enalaprilat group (p <0.05). Thus, in this pilot study, intracoronary
enalaprilat infusion in the
infarct-related artery is feasible in the setting of primary angioplasty and is safe and well tolerated. Effective cardiac ACE inhibition can be achieved by low-dose intracoronary
enalaprilat, which primarily causes a potentiation of
bradykinin.