High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size.
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors differ in their ability to inhibit tissue ACE. This study was, therefore, undertaken to determine whether high tissue affinity ACE inhibitors would improve endothelial function and thereby decrease tissue necrosis during ischemia.


METHODS
In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the period of coronary occlusion, 10 pigs received enalaprilat (low affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received no ACE inhibitor.


RESULTS
Wall motion scores (4, normal, to -1, dyskinesia) were higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus 3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE). Endothelial-dependent relaxation to bradykinin was best preserved in the quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6% quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from enalaprilat). This was associated with a greater reduction in infarct size: area necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus 14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat) versus 40.0%+/-1.7% no ACE.


CONCLUSIONS
ACE inhibitors with higher affinity to tissue ACE result in better preservation of endothelial function and less tissue necrosis during coronary revascularization.
Lazar
H L
HL
Department of Cardiothoracic Surgery, Boston University School of Medicine, Boston Medical Center, Massachusetts 02118, USA. harold.lazar@bmc.org
Bao
Y
Y
Rivers
S
S
Colton
T
T
Bernard
S A
SA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015773:Enalaprilat / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D013552:Swine; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C054501:quinaprilat; D015773:Enalaprilat