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Ann Thorac Surg 1999;67:1538-1539
© 1999 The Society of Thoracic Surgeons


Correspondence

Aprotinin-enhanced lung preservation solutions: is it worthwhile

Thorsten Wittwer, MDa, Thorsten Wahlers, MDa, Sebastian Elkia, Axel Haverich, MDa

a Department of Cardiothoracic and Vascular Surgery, Hannover Medical School, Carl-Neuberg-St 1, 30625 Hannover, Germany

e-mail: Th.Wittwer-MD{at}t-online.de

To the Editor

Although lung transplantation is now regarded as an effective therapy in end-stage pulmonary disease, its application is limited by the severe scarcity of suitable donor organs. With the approach to extend the donor pool, adequate preservation of the donor organ is still an important issue to enhance the applicability of the procedure with the aim to reduce perioperative mortality due to organ dysfunction.

Currently, most institutions use single-flush perfusion with extracellular type preservation solutions via the pulmonary artery for lung preservation. Recent research described that the addition of the serine protease inhibitor Aprotinin to the preservation solution significantly improves postischemic lung function [1]. While the authors of those experiments used Euro-Collins and University of Wisconsin solution, others reported similar findings after administration of recombinant Kunitz protease inhibitor, which is more homologous to human Kunitz protease inhibitor as compared with Aprotinin, to low-potassium dextran solution [2].

To verify the demonstrated benefit, Aprotinin was used in an established isolated rat lung model [3, 4] to elucidate if the combination with the recently developed Celsior solution would provide similar preservation results as compared with modified Euro-Collins solution [5]. Using male inbred Sprague-Dawley rats, eight lungs each were preserved with Celsior solution with and without addition of Aprotinin in the described dose of 150 KIU/mL as suggested by Roberts and associates [1] and compared with Perfadex solution. After 4 h of ischemia, all lungs were reventilated and reperfused using a roller-pump. Oxygenation as assessed by relative oxygenation capacity (ROC = [paO2 - pvO2] x 100/pvO2) was monitored for a reperfusion period of 50 min. Statistical analysis was performed using analysis of variance with repeated measures.

After ischemia, all reperfused lungs resumed sufficient function. However, the ROC of Celsior-preserved organs was significantly better as compared with the corresponding Perfadex preservation (Fig 1). After additional application of Aprotinin, a significant deterioration of postischemic lung performance in the Celsior group was noticed (p = 0.02), while graft function in the Perfadex+Aprotinin group was not significantly altered (p = 0.62). With use of Aprotinin, both solutions (Celsior/Perfadex) led to a comparable quality of organ preservation (p = 0.39).



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Fig 1. Relative oxygenation capacity (ROC = [paO2 - pvO2] x 100/pvO2) of postischemic rat lungs after 50 min of reperfusion. Preservation groups were comprised of Celsior (CE), Perfadex (PER), Celsior with Aprotinin (CE+A), and Perfadex with Aprotinin (PER+A).

 
Aprotinin has been shown to be protective against the damage of ischemia and reperfusion by its antiproteolytic and lysosomal membrane-stabilizing properties [1]. In our series, however, no beneficial effect was noticed when Perfadex was used for lung preservation. Furthermore, after organ preservation with Celsior and additional Aprotinin, a significant deterioration of postischemic organ function was noticed. One of the reasons for the latter observation is given by the composition of Celsior solution. Celsior is designed to prevent cell swelling, free radical injury, calcium overload, and energy depletion by use of lactobionate, mannitol, histidine, and reduced gluthathione. This might not allow it to be combined with the specific effects of additional Aprotinin. However, the exact mechanism by which Aprotinin significantly deteriorates the lung function of Celsior-protected organs is unclear. As a consequence, additional stereological and ultrustructural studies have to be initiated to further elucidate this relevant mechanism.

In conclusion, the clinical application of Aprotinin in combination with other preservation solutions should be performed carefully until further data are available.

References

  1. Roberts R.F., Nishanian G.P., Carey J.N., et al. Addition of Aprotinin to organ preservation solution decreases lung reperfusion injury. Ann Thorac Surg 1998;66:225-230.[Abstract/Free Full Text]
  2. Nagahiro I., White T., Yano M., et al. Recombinant Kunitz protease inhibitor ameliorates reperfusion injury in rat lung transplantation. Ann Thorac Surg 1998;66:351-355.[Abstract/Free Full Text]
  3. Albes J.M., Fischer F., Bando T., Heinemann M.K., Scheule A., Wahlers T. Influence of the perfusate temperature on lung preservation: is there an optimum?. Eur Surg Res 1997;29:5-11.[Medline]
  4. Bando T., Albes J.M., Nuesse T., et al. Comparison of Euro-Collins solution, low-potassium dextran solution containing glucose, and ET-Kyoto solution for lung preservation in an extracorporeal rat lung perfusion model. Eur Surg Res 1998;30:297-304.[Medline]
  5. Wittwer T, Wahlers T, Fehrenbach A, et al. Combined use of prostacyclin and higher perfusate temperatures further enhances the superior lung preservation by Celsior solution in the isolated rat lung. J Heart Lung Transplant 1999; in press.

Related Article

Reply
Mark L. Barr
Ann. Thorac. Surg. 1999 67: 1539-1540. [Extract] [Full Text] [PDF]




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