Angiotensin-converting enzyme inhibition alters the fibrinolytic response to cardiopulmonary bypass.
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.


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.
Pretorius
Mias
M
Department of Anesthesiology, Vanderbilt University, Nashville, Tenn, USA. mias.pretorius@vanderbilt.edu
Murphey
Laine J
LJ
McFarlane
Julie A
JA
Vaughan
Douglas E
DE
Brown
Nancy J
NJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D003131:Combined Modality Therapy; D001026:Coronary Artery Bypass; D005260:Female; D005342:Fibrinolysis; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator