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Ann Thorac Surg 1996;62:317-318
© 1996 The Society of Thoracic Surgeons
Department of Surgery MeritCare Hospital of Fargo and UND School of Medicine 720 4th St N Fargo, ND 58122
To the Editor:
We read with interest the report by Basu and associates [1] entitled "Comparative Study of Biological Glues: Cryoprecipitate Glue, Two-Component Fibrin Sealant, and `French Glue'." The observation that cryoprecipitate-thrombin (CT), a weak tissue adhesive, was as effective, if not more so, than stronger tissue adhesives in sealing of aortic and atrial suture lines at 30 seconds after application was of interest. We are hesitant, however, in accepting their suggestion that this finding justifies the general recommendation that CT "can be used when hemostatic action is the only requirement."
After some frustrating experience with CT for cardiac surgical suture line sealing and for topical hemostasis in burn wound debridement, we undertook screening experiments in rabbits before and after heparin administration (100 units/kg intravenously) (unpublished observations). We tested various topical hemostatic material in sealing of aortic suture lines, graded splenic injuries, and skin graft wounds. The effectiveness of CT was erratic, and CT was reliable only when fibrinogen concentration was augmented (>50 mg/mL). This was subsequently confirmed clinically in a comparison of the effectiveness of CT and a commercial fibrin sealant (Tissel, Immuno AG, New York, NY; fibrinogen > 80 mg/mL) in infants and children undergoing similar operative procedures.
Basu and associates note that the finding that stronger tissue adhesives, such as "French" glue (gelatin-resorcin-formol), effectively seal with longer set times but at the risk of adverse tissue reaction was not unexpected. However, the observation of more rapid resorption of two-component fibrin sealant relative to CT was unexpected as the former contains aprotinin, and suggests that factors such as various fibrin mesh structures may be important in determining resorption rates [2].
The general statement by Basu and associates that there are no known contraindications to the use of biological glues is one we cannot accept. In addition to this study, others have observed possible adverse effects of gelatin-resorcin-formol components in tissues such as the cardiac conduction system and lung [3–5]. In addition, as noted by Basu and associates, topical animal-derived thrombins have on occasion induced an "immune coagulopathy" in humans. Experimentally, impairment of wound healing is easily induced with many proposed tissue adhesives. This study suggests the usefulness as well as a potential limitation of these tissue adhesives. As Basu and associates imply, perhaps the nonavailability of commercial tissue adhesive in the United States has limited study of these materials. Various efforts to develop improved tissue adhesives are underway. As such investigations usually require the support of industry, the results of ongoing investigations often are not published because of proprietary concerns.
General references in this area of technology are available [2, 5, 6] and suggest various approaches to obtain high-strength, biocompatible adhesives. Proposals of which we are aware include use of rapid, efficient cryoprecipation and lyophilization for processing plasma units (Instacool, Inc, San Diego, CA; Stryker Corp, Kalamazoo, MI) and use of recombinant coagulation proteins (Zymogenetics, Seattle, WA). In addition, studies in a rabbit skin graft model have demonstrated that use of chemically modified thrombin fibrin sealants permits more efficient fibrinogen conversion with a high degree of biocompatibility (Cryolife Inc, Marietta, GA).
Experimental studies and limited clinical experience have indicated that various modified protein polymers and cross-linking agents permit production of tissue adhesives with tissue bonding strengths equal or superior to those of gelatin-resorcin–based materials but with improved degrees of biocompatibility. Such materials are the subject of ongoing development (Cryolife Inc).
For these reasons we would encourage interested surgeons to undertake further investigations in this area. As the study by Basu and associates demonstrates, such investigations are valuable in developing a better understanding of these materials and proposed applications.
References
Maimonides Medical Center 4820 Tenth Ave Brooklyn, Ny 11219
To the Editor:
We thank Drs Browdie and Bernstein for their comments on two points of our study of biological glues [1].
Their first concern involved our statement that cryoprecipitate glue can be used when hemostatic action is the only requirement. Our experimental model, designed to test the hemostatic efficacy of the three glues, was one where sutures were placed 3 mm apart and the application of the glue followed reclamping; therefore, the resulting condition was one where oozing rather than pulsatile bleeding was present. Our statement, "when hemostatic action is the only requirement, one can use either the cryoprecipitate glue or the two-component fibrin sealer," pertains to those instances where there is diffuse oozing not pulsatile bleeding. This conclusion is based on our results and from first-hand observations made during operative procedures performed in European centers. As stated in our article, the cryoprecipitate glue has inadequate tensile strength to provide an adequate mechanical barrier to stop pulsatile bleeding.
The second concern expressed by Drs Browdie and Bernstein pertains to our statement that there are no known contraindications to the use of biological glues. They correctly report that others have observed side effects on the cardiac system and lung [2, 3]. We would like to emphasize that there are side effects associated with the incorrect use of biological glues: Carrel and associates [4] reported catastrophic distal embolization after the use of the "French glue," whereas Von Oppell and colleagues [5] experienced 2 cases of complete heart block from spillage into the aorto-atrial area, caused by the aldehyde components present in the glue. These technically preventable side effects, however, do not contraindicate the use of biological glues.
References
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