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Ann Thorac Surg 2001;72:548-553
© 2001 The Society of Thoracic Surgeons


Original article: cardiovascular

High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size

Harold L. Lazar, MDa, Yusheng Bao, MDa, Samuel Rivers, BSa, Theodore Colton, ScDa, Sheilah A. Bernard, MDa

a Department of Cardiothoracic Surgery, Boston University School of Medicine, and the Boston Medical Center, Boston, Massachusetts, USA

Accepted for publication April 17, 2001.

Address reprint requests to Dr Lazar, Department of Cardiothoracic Surgery, Boston Medical Center, Suite B404, 88 E Newton St, Boston, MA 02118
e-mail: harold.lazar{at}bmc.org

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.


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Invited commentary
David G. Cable
Ann. Thorac. Surg. 2001 72: 553-554. [Extract] [Full Text] [PDF]



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