Ann Thorac Surg 2006;82:1951-1952
© 2006 The Society of Thoracic Surgeons
Correspondence
Reply
Robert Poston, MD,
Ozeki Toshinaga, PhD
Division of Cardiac Surgery, University of Maryland School of Medicine, N4W94 22 S. Greene St, Baltimore, MD 21201
(Email: rposton{at}smail.umaryland.edu).
To the Editor:
As suggested by Vanek and colleagues [1], a growing body of evidence supports the safety of aprotinin use during OPCAB. Their own report [2], published while our off-pump coronary artery bypass (OPCAB) trial in The Annals of Thoracic Surgery was in press [3], highlights two points that are becoming increasingly clear about aprotinin. First, aprotinin provides a hemostatic benefit that exceeds the lysine analogues, likely due to the ability to preserve platelet function in addition to blocking fibrinolysis. Second, aprotinin does not create a hypercoagulable tendency. The clinical safety of aprotinin use during high risk groups such as OPCAB, vascular [4], and orthopedic surgery [5], and its ability to modulate the thrombin receptor, protease-activated receptor-1 (PAR-1) [6], provide strong evidence to the contrary. In fact, it is these patients who are at greatest risk for perioperative hypercoagulability and the propensity to generate thrombin in which the impact of PAR-1 inhibition by aprotinin may be most relevant.
In their letter, Vanek and colleagues [1] raise the intriguing notion that a significant reduction in troponin I release after aprotinin use in both of our trials may represent a clinical antithrombic effect during OPCAB. Randomized trials done in on-pump coronary artery bypass grafting patients have shown no difference in troponin I or other myocardial injury markers after aprotinin administration [7]. During cold, cardioplegic arrest, troponin I release is confounded by variations in the quality of myocardial preservation and does not solely reflect intracoronary thrombosis. On the other hand, brief, regional warm ischemia incurred during OPCAB activates inflammatory and thrombotic pathways that have been shown to be influenced by aprotinin in several animal models [8–10]. We recently reanalyzed the subset of our cohort that had coronary sinus samples obtained to define the impact of aprotinin on these pathways by comparing the difference in the transcardiac release (ie, coronary sinus—aortic levels) of markers of cardiac inflammation and injury. In addition to a significant reduction in the gradient of the thrombin formation marker F1.2 (already reported), the aprotinin group showed trends toward a reduction in the release of a number of these markers immediately after OPCAB (see Table 1). These data suggest the mechanism for the reduction in troponin I in both of our OPCAB studies may be related to the ability of aprotinin to help protect the myocardium against brief warm ischemia. This benefit may prove valuable in the growing population of OPCAB referrals with limited myocardial reserve.
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References
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- Vanek T, Jares M, Straka Z, MSM0021620817 Study Group Aprotinin reduces troponin I levels in OPCABG(letter) Ann Thorac Surg 2006;82:1950-1951.[Free Full Text]
- Vanek T, Jares M, Fajt R, et al. Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo) Eur J Cardiothorac Surg 2005;28:563-568.[Abstract/Free Full Text]
- Poston RS, White Ch, Gu J, et al. Aprotinin shows both hemostatic and antithrombotic effects during off-pump coronary artery bypass grafting Ann Thorac Surg 2006;81:104-111.[Abstract/Free Full Text]
- Robinson J, Nawaz S, Beard JD, Joint Vascular Research Group Randomized, multicentre, double-blind, placebo-controlled trial of the use of aprotinin in the repair of ruptured abdominal aortic aneurysm Br J Surg 2000;87:754-757.[Medline]
- Shiga T, Wajima Z, Inoue T, Sakamoto A. Aprotinin in major orthopedic surgery: a systematic review of randomized controlled trials Anesth Analg 2005;101:1602-1607.[Abstract/Free Full Text]
- Day JR, Taylor KM, Lidington EA, et al. Aprotinin inhibits proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1 J Thorac Cardiovasc Surg 2006;131:21-27.[Abstract/Free Full Text]
- Taggart DP, Djapardy V, Naik M, Davies A. A randomized trial of aprotinin (Trasylol) on blood loss, blood product requirement, and myocardial injury in total arterial grafting J Thorac Cardiovasc Surg 2003;126:1087-1094.[Abstract/Free Full Text]
- Gurevitch J, Barak J, Hochhauser E, et al. Aprotinin improves myocardial recovery after ischemia and reperfusion: effects of the drug on isolated rat hearts J Thorac Cardiovasc Surg 1994;108:109-118.[Abstract/Free Full Text]
- Khan TA, Bianchi C, Voisine P, et al. Reduction of myocardial reperfusion injury by aprotinin after regional ischemia and cardioplegic arrest J Thorac Cardiovasc Surg 2004;128:602-608.[Abstract/Free Full Text]
- Lazar HL, Bao Y, Tanzillo L, et al. Aprotinin decreases ischemic damage during coronary revascularization J Card Surg 2005;20:519-523.[Medline]
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Aprotinin Reduces Troponin I Levels in OPCABG
- Tomas Vanek, Martin Jares, Zbynek Straka MSM0021620817 Study Group
Ann. Thorac. Surg. 2006 82: 1950-1951.
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