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Ann Thorac Surg 1996;61:1039-1040
© 1996 The Society of Thoracic Surgeons

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Correspondence

Topical Aprotinin in Cardiac Operations: A Note of Caution

Section of Cardiovascular Surgery, Mayo Clinic, 200 First St, Sw, Rochester, Mn 55905

To the Editor:

Topical use of aprotinin has recently been shown to reduce postoperative blood loss in patients undergoing cardiac operations [1, 2]. It has been suggested that a local fibrinolytic state persists after closure of the thoracic cavity and contributes to the postoperative blood loss [3]. Topical aprotinin seems to exert an antifibrinolytic action and potentially stabilizes fibrin sealing of the surgical wound [4].

The number of reoperations has been steadily increasing with the expanding volume of cardiac surgery. Reoperations carry higher morbidity and mortality. The reported incidence of severe hemorrhage during sternal reentry is 2% to 6% [5]. The presence of dense mediastinal adhesions at reoperation obscures the cardiac anatomy and complicates the dissection, increasing the risk of injury to coronary bypass grafts, extracardiac conduits, great vessels, or even the heart itself. Furthermore, adhesions may have a deleterious effect on cardiac function and lead to decreased graft patency [6, 7].

Mesothelial cells are known to secrete physiologically abundant tissue-type plasminogen activator (t-PA) and therefore have an actual or potential role in preventing formation of the adhesions between organs [8, 9]. Porter and associates [10] and Gervin and associates [11] demonstrated the fibrinolytic properties of the mesothelial pericardial tissue. Nkere and colleagues [12, 13] have recently shown significant reductions in pericardial t-PA and plasminogen activating activity during cardiopulmonary bypass. They also suggested that reduction of local fibrinolytic activity associated with pericardial damage may contribute to development of fibrous pericardial adhesions.

Several methods have been tried to reduce postoperative pericardial adhesion formation. Fibrinolytic drugs have been widely investigated for the reduction of adhesions, especially in the abdominal cavity. Dorr and associates [14] demonstrated that enhancing fibrinolytic activity with topical t-PA after mesothelial injury may prevent adhesion formation in the peritoneum. Cross and colleagues [15] reported the successful use of intrapericardial streptokinase to aid in drainage of postoperative loculated pericardial effusion. More recently, Wiseman and co-workers [16] have used fibrinolytic agents t-PA, a t-PA analogue (Fb-Fb-CF), and streptokinase in a rabbit pericardial adhesion model. Adhesions of the anterior cardiac surface were reduced in area from 89% in controls to 28% by treatment with t-PA analogue and 49% by treatment with streptokinase. The results of these studies support the view that there at least is a component of impaired or reduced fibrinolytic activity in adhesion formation.

In their recent study published in The Annals, O'Regan and associates [2] hypothesized that postoperative pericardial adhesion formation may be inhibited by topical aprotinin therapy. However, aprotinin is shown to inhibit plasmin and kallikrein and to inactivate anticoagulant factor protein C, and thus functions as an antifibrinolytic agent. Current data suggest that pericardial adhesion formation is highly dependent on fibrin deposition or impairment of mesothelial fibrinolytic activity. We therefore propose that although topical aprotinin has clearly been beneficial in reducing postoperative mediastinal bleeding in cardiopulmonary bypass cases, its use in the pericardial cavity may enhance postoperative mediastinal adhesion formation through its antifibrinolytic effects.

References

1. Tatar H, Çiçek S, Demirkiliç U, et al. Topical use of aprotinin in open heart operations. Ann Thorac Surg 1993;55:659–61.[Abstract]
2. O'Regan DJ, Giannopoulos N, Mediratta N, et al. Topical aprotinin in cardiac operations. Ann Thorac Surg 1994;58:778–81.[Abstract]
3. Tabuchi N, de Haan J, Boonstra PW, van Oeveren W. Activation of fibrinolysis in the pericardial cavity during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;106:828–33.[Abstract]
4. Çiçek S, Tatar H, Demirkiliç U, Kuralay E. Topical use of aprotinin in cardiac surgery. J Thorac Cardiovasc Surg 1995;110:568–9.[Free Full Text]
5. Dobell ARC, Jain AK. Catastrophic hemorrhage during redo sternotomy. Ann Thorac Surg 1984;37:273–8.[Abstract]
6. Bailey LL, Li Z, Schulz E, Roost H, Yahiku P. A cause of right ventricular dysfunction after cardiac operations. J Thorac Cardiovasc Surg 1984;87:539–42.[Abstract]
7. Shapira N, Gordon CI, Lemole GM. Occlusion of aortocoronary vein grafts in association with bovine pericardium. Am J Cardiovasc Pathol 1989;3:87–90.
8. Whitaker D, Papadimitrou M, Walters MNI. The mesothelium: its fibrinolytic properties. J Pathol 1982;136:291–9.[Medline]
9. Van Hinsberg VWM, Kooistra T, Scheffer MA, van Bockel JH, van Muijen GNP. Characterization and fibrinolytic properties of human omental tissue mesothelial cells: comparison with endothelial cells. Blood 1990;75:1490–7.[Abstract/Free Full Text]
10. Porter JM, Ball AP, Silver D. Mesothelial fibrinolysis. J Thorac Cardiovasc Surg 1971;62:725–30.[Medline]
11. Gervin AS, Jacobs G, Hufnagel HV, Mason KG. Surgical trauma and pericardial fibrinolytic activity. Am Surg 1975;41:225–9.[Medline]
12. Nkere UU, Whawell SA, Thompson EM, Thompson JN, Taylor KM. Changes in pericardial morphology and fibrinolytic activity during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;106:339–45.[Abstract]
13. Nkere UU, Whawell SA, Sarraf CE, Schofield JB, Thompson JN, Taylor KM. Perioperative histologic and ultrastructural changes in the pericardium and adhesions. Ann Thorac Surg 1994;58:437–44.[Abstract]
14. Dorr PJ, Vemer HM, Brommer EJ, Willemsen WN, Veldhuizen RW, Rolland R. Prevention of postoperative adhesions by tissue-type plasminogen activator (t-PA) in the rabbit. Eur J Obstet Gynecol Reprod Biol 1990;37:287–91.[Medline]
15. Cross JH, DeGiovanni JV, Silove ED. Use of streptokinase to aid in the drainage of postoperative pericardial effusion. Br Heart J 1989;62:217–9.[Abstract/Free Full Text]
16. Wiseman DM, Kamp L, Linsky CB, Jochen RF, Pang RHL, Scholz PM. Fibrinolytic drugs prevent pericardial adhesions in the rabbit. J Surg Res 1992;53:362–8.[Medline]

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This Article Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Sertaç Çiçek David A. Theodoro Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Çiçek, S. Articles by Theodoro, D. A. Search for Related Content PubMed PubMed Citation Articles by Çiçek, S. Articles by Theodoro, D. A.