Published Online
on December 1, 2003

A more recent version of this article appeared on December 23, 2003

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Submitted on July 22, 2003
Revised on September 23, 2003
Accepted on September 25, 2003

Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass

Mias Pretorius MBChB, MSc^*, Laine J. Murphey MD, PhD, Julie A. McFarlane RN, Douglas E. Vaughan MD, and Nancy J. Brown MD

From the Department of Anesthesiology (M.P., J.A.M.), Divisions of Clinical Pharmacology (L.J.M., N.J.B.) and Cardiovascular Medicine (D.E.V.), Departments of Medicine and Pharmacology, Vanderbilt University, and Veterans Affairs Medical Center (M.P., D.E.V.), Nashville, Tenn.

^* To whom correspondence should be addressed. E-mail: mias.pretorius{at}vanderbilt.edu.

Background--Increased plasminogen activator inhibitor-1 (PAI-1) concentrations after coronary artery bypass grafting (CABG) are associated with increased risk of vein graft occlusion. Because angiotensin II stimulates PAI-1 expression, we tested the hypothesis that preoperative angiotensin-converting enzyme (ACE) inhibition decreases PAI-1 expression after CABG.

Methods and Results--We measured the effects of cardiopulmonary bypass (CPB) on PAI-1 antigen and tissue-type plasminogen activator (tPA) antigen and activity in 31 patients taking an ACE inhibitor (ACEI) who were randomized to continue ACEI until the morning of surgery (ACEI group, n=19) or to discontinue it 48 hours before surgery (No-ACEI group, n=12). Arterial blood samples were taken at baseline before CPB, twice during CPB, after separation from CPB, and on postoperative day 1 (POD1). CPB caused an early decrease in PAI-1 antigen, followed by an increase in PAI-1 antigen on POD1 (P<0.001 for effect of time). ACE inhibition attenuated the increase in PAI-1 antigen such that both PAI-1 antigen on POD1 (P=0.013) and the change in PAI-1 antigen from baseline to POD1 (P=0.009) were higher in the No-ACEI group (from 17.0±5.0 to 48.7±8.8 ng/mL) versus the ACEI group (from 19.9±3.4 to 33.1±6.2 ng/mL). There was no significant difference between the 2 groups in intraoperative tPA activity (P=0.259); however, the increase in tPA activity was significantly greater in the ACEI group than in the No-ACEI group (P=0.030).

Conclusions--Preoperative ACEI attenuates the increase in PAI-1 after CABG, suggesting a role for ACE inhibition in reducing the risk of acute graft thrombosis.

Key words: plasminogen activators • inhibitors • angiotensin • cardiopulmonary bypass • thrombosis

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