Effects of intracoronary low-dose enalaprilat as an adjunct to primary percutaneous transluminal coronary angiography in acute myocardial infarction.
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.
Kurz
T
T
Medizinische Klinik II, Universitätsklinikum Lübeck, Lübeck, Germany. kurz@medinf.mu-luebeck.de
Schäfer
U
U
Dendorfer
A
A
Hartmann
F
F
Raasch
W
W
Tölg
R
R
Remppis
A
A
Giannitsis
E
E
Dominiak
P
P
Katus
H A
HA
Richardt
G
G
D015906:Angioplasty, Balloon, Coronary; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D004357:Drug Synergism; D004562:Electrocardiography; D015773:Enalaprilat / Q000008:administration & dosage*; D006439:Hemodynamics; D006801:Humans; D007262:Infusions, Intravenous; D009203:Myocardial Infarction / Q000188:drug therapy*; D010865:Pilot Projects; D051381:Rats; D016277:Ventricular Function, Left
D000806:Angiotensin-Converting Enzyme Inhibitors; D015773:Enalaprilat; D001920:Bradykinin