HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tabuchi, N. Articles by van Oeveren, W. Search for Related Content PubMed PubMed Citation Articles by Tabuchi, N. Articles by van Oeveren, W.

J Thorac Cardiovasc Surg 1995;109:399-400
© 1995 Mosby, Inc.

LETTERS TO THE EDITOR

Topical effect of aprotinin on the surgical wound in cardiac surgery

Thoraxcenter
Blood Interaction Research
University Hospital Groningen
Groningen, The Netherlands

To the Editor:

The best way to apply aprotinin is unknown in cardiac surgery, because the mechanism of aprotinin in preserving hemostasis remains under investigation. ^1,2 We have been recommending the use of low-dose aprotinin (2 million KIU) in the pump prime, because we demonstrated that low-dose aprotinin is sufficient to preserve platelet glycoprotein Ib receptors ³ and ristocetinagglutination capacity of platelets ⁴ during cardiopulmonary bypass (CPB). These seem to be the main mechanisms of aprotinin in preserving hemostasis. This efficacy and the sufficiency of low-dose aprotinin were reproduced by the platelet aggregation model on the extracellular matrix. ⁵ Another possible mechanism of aprotinin in preserving hemostasis is the preservation of fibrin hemostatic sealing by the inhibition of fibrinolysis. ¹ However, the direct effect of fibrinolysis inimpairing hemostasis remains unclear, ¹ because no clear evidence has been collected regarding how much the increase of fibrin-split products in the systemic circulation stands for the lysis of fibrin hemostatic sealing on the wound surface.

Of great interest is a recent report of Tatar and associates, ⁶ who demonstrated the efficacy of aprotinin (1 million KIU) on hemostasis when used topically in the pericardial cavity before closure of the thorax cavity. This observation certainly suggests that the inhibition of fibrinolysis on the closed thorax cavity stabilizes the fibrin hemostatic sealing on the wound surface, contributing to hemostasis. If aprotinin is applied topically, its effect seems solely based on antifibrinolysis. In a previous study, we ⁷ demonstrated enormous activation of fibrinolysis on the surgical wound by sampling blood from the thoracic cavity. This method might reveal the topical effect of aprotinin on the wound surface, proving the hypothesis that a stable fibrin sealing of the wound prevents postoperative bleeding.

Therefore, we conducted a study in 12 patients undergoing coronary artery bypass grafting randomly treated with placebo or low-dose aprotinin in the pump prime. The blood oozing from the surgical wound was collected in the pericardial cavity and sampled during creation of the distal coronary anastomoses. Blood samples from the systemic circulation were taken simultaneously for comparison. An enormous increase of fibrin degradation products was observed in the blood of the surgical wound compared with systemic blood (p < 0.01) (Table I). Likely, the increased fibrin degradation products in the blood from the surgical wound represents the lysis of the fibrin hemostatic sealing on the wound surface. Aprotinin reduced fibrin degradation products in wound blood only by half (p < 0.01) (Table I). This result indicates that systemically applied low-dose aprotinin could reduce but not prevent lysis of hemostatic fibrin sealing on the wound surface during CPB. Moreover, after closure of the thoracic cavity this fibrinolytic state could be even more intensified by the increased activity of tissue-plasminogen activator from the pericardium. ⁸ Therefore the topical use of aprotinin before closure of the thoracic cavity could be most effective in preserving fibrin hemostatic sealing on the wound surface. The scheme for low-dose aprotinin was designed to preserve platelet function during CPB ³ but not to maintain the antifibrinolytic capacity after closure of the thoracic cavity. Therefore use of topical aprotinin might be recommended in addition to low-dose use in the pump prime to amplify the hemostatic capacity of aprotinin by two mechanisms: preserving platelet function during CPB and preserving fibrin hemostatic sealing after closure of the thoracic cavity.

1. Edmunds LH Jr. Aprotinin use in pediatric cardiac operations. J THORAC CARDIOVASC SURG 1993;105:757-8.[Medline]
   
2. Edmunds LH Jr. Aprotinin's effect in cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1993;106:748-9.[Medline]
   
3. van Oeveren W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CRH. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1990;99:788-97.[Abstract]
   
4. Tabuchi N, de Haan J, Boonstra PW, Gallandat Huet RCG, van Oeveren W. Aprotinin effect on platelet function and clotting during cardiopulmonary bypass. Eur J Cardiothorac Surg 1994;8:87-90.[Abstract/Free Full Text]
   
5. Mohr R, Goor DA, Lusky A, Lavee J. Aprotinin prevents cardiopulmonary bypass-induced platelet dysfunction. Circulation 1992;86(Suppl):II405-9.
   
6. Tatar H, Cicek S, Demirkilic U, et al. Topical use of aprotinin in open heart operations. Ann Thorac Surg 1993;55:659-61.[Abstract/Free Full Text]
   
7. 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]
   
8. de Haan J, Schönberger JPAM, Haan J, van Oeveren W, Eijgelaar A. Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during reperfusion of shed blood after cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1993;106:1017-23.[Abstract]
   

This article has been cited by other articles:

				L. H. Edmunds Jr Managing Fibrinolysis Without Aprotinin Ann. Thorac. Surg., January 1, 2010; 89(1): 324 - 331. [Abstract] [Full Text] [PDF]

				N. Hayashida, T. Isomura, T. Sato, H. Maruyama, K. Kosuga, and S. Aoyagi EFFECTS OF MINIMAL-DOSE APROTININ ON CORONARY ARTERY BYPASS GRAFTING J. Thorac. Cardiovasc. Surg., August 1, 1997; 114(2): 261 - 269. [Abstract] [Full Text]

				S. Cicek, H. Tatar, U. Demirklc, and E. Kuralay Topical use of aprotinin in cardiac surgery J. Thorac. Cardiovasc. Surg., August 1, 1995; 110(2): 568 - 569. [Full Text]

				L. H. Edmunds Jr. Invited letter concerning: Topical aprotinin J. Thorac. Cardiovasc. Surg., February 1, 1995; 109(2): 400 - 401. [Full Text]

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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tabuchi, N. Articles by van Oeveren, W. Search for Related Content PubMed PubMed Citation Articles by Tabuchi, N. Articles by van Oeveren, W.