Ann Thorac Surg 2004;77:338-339
© 2004 The Society of Thoracic Surgeons
Case report
Application of ET-Kyoto solution in clinical lung transplantation
Mitsugu Omasa, MDa,
Seiki Hasegawa, MD, PhDa*,
Toru Bando, MD, PhDa,
Nobuharu Hanaoka, MDa,
Takashi Yoshimura, MD, PhDa,
Takayuki Nakamura, MD, PhDa,
Hiromi Wada, MD, PhDa
a Department of Thoracic Surgery, Kyoto University, Kyoto, Japan
Accepted for publication April 29, 2003.
* Address reprint requests to Dr Shiraishi, Division of Pediatrics, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan 602-8566.
e-mail: isao{at}koto.kpu-m.ac.jp
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Abstract
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We have developed a new organ preservation solution called extracellular-type trehalose-containing Kyoto (ET-Kyoto) solution. ET-Kyoto solution has been applied in clinical lung transplantation. The patient was a 49-year-old woman with diffuse panbronchiolitis. She underwent bilateral lobar lung transplantation from living donors. Each lobe was flushed with ET-Kyoto solution. After reperfusion, PaO2 with inhalation of 100% oxygen was more than 500 Torr. Posttransplantation course was uneventful. Despite the relatively short ischemic time of this case report, ET-Kyoto solution may be feasible and safely applied in clinical lung transplantation.
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Introduction
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We have developed a new organ preservation solution called extracellular-type trehalose-containing Kyoto (ET-Kyoto) solution. We herein report results from using ET-Kyoto solution during clinical lung transplantation.
The patient was a 49-year-old Japanese woman in whom diffuse panbronchiolitis developed in 1996. She had been in critical condition because of persistent pseudomonas infection for more than a year. She underwent bilateral lobar lung transplantation on cardiopulmonary bypass from living donors (her husband and son) whose blood type was not identical to the recipient (recipient: B, donors: O) in April 2002. Each lower lobe was flushed smoothly and homogeneously with 2000 mL ET-Kyoto solution (1500 mL antegradely and 500 mL retrogradely) until no pinkish area was left. Both donor lungs were simultaneously reperfused with an ischemic time of 248 minutes for the right lower lobe and 141 minute for the left lower lobe. Reperfusion of both lungs was smooth and no apparent area of poor reperfusion existed. When cardiopulmonary bypass was totally weaned with the cardiopulmonary bypass time of 328 minutes after 40 minutes of reperfusion, PaO2 and PaCO2 with inhalation of 100% oxygen were 525 and 23.2 Torr, respectively. PaO2 with inhalation of 100% oxygen was maintained at mo/re than 450 Torr for longer than 2 weeks despite acute rejection on days 4 and 11. Currently (12 months after/ surgery), she is doing well in her daily life without a sign of chronic rejection on chest computed tomography or bronchofiberscopy.
Clinical application of ET-Kyoto solution was approved by the Ethics Committee at Kyoto University and the informed consent was obtained from the patient and both of the donors.
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Comment
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ET-Kyoto solution used in this case was the conventional ET-Kyoto solution, which had been stored at room temperature for more than 1 year and blended with nitroglycerin (NTG) and dibutyryl adenosine 3', 5'-cyclic monophosphate (db-cAMP) just before pulmonary vasculature flush (Table 1).
We have developed new organ preservation solutions [1] that have been used with good results during experimental lung transplantation [2–6]. ET-Kyoto solution has three characteristic features. First, it has an extracellular ion composition. Next, trehalose is used as a saccharide. Third, NTG and db-cAMP are supplemented to protect the vascular endothelium.
Euro-Collins and University of Wisconsin solutions, each of which has an intracellular ion composition, have been the primary solutions used for clinical lung transplantation. However, we have found that an extracellular-type solution is superior to an intracellular type, first by comparing our ET-Kyoto and the intracellular-type trehalose-containing Kyoto solutions [2], and second in a comparison of ET-Kyoto solution with Euro-Collins and University of Wisconsin solutions, in which ET-Kyoto solution had a preservative effect that was better than that of Euro-Collins solution and equal to that of University of Wisconsin solution [3].
Trehalose is a nonreducing disaccharide that exists in many prokaryotes, fungi, yeasts, some desert plants, and insect body fluid. Although saccharides are usually considered to be osmotic impermeant and to act as energy sources during ischemia, trehalose protects the cells under various nonphysiologic conditions by stabilizing the cell membrane and creating a stable environment around the cell. Furthermore, we showed that trehalose has a superior preservative effect as compared with the other saccharides [7] and that ET-Kyoto solution provided superior preservation to that of low-potassium-dextran-glucose, an extracellular-type preservation solution [4].
It is well known that the protection of the vascular endothelium is important for organ preservation. We added NTG and db-cAMP to the conventional ET-Kyoto solution because these two substances were proven to protect the pulmonary artery endothelium in previous experiments [5, 6].
We have now started clinical application of ET-Kyoto solution in the preservation of severed fingers. Furthermore, we plan to use ET-Kyoto solution for renal storage based on our experimental data [8].
Although this is only a case report with a relatively short ischemic time, our findings demonstrate that ET-Kyoto solution may be feasible for clinical lung transplantation. ET-Kyoto solution could be used, not only because of its excellent preservation ability but also because of its better handling and economical benefit in comparison with other solutions.
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References
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- Wada H., Omasa M., Nakamura T. Development of new organ preservation solutions and their application. Recent Res Devel Resp Crit Care Med 2002;2:181-193.
- Bando T., Kosaka S., Liu C., et al. Effects of newly developed solutions containing trehalose on twenty-hour canine lung preservation. J Thorac Cardiovasc Surg 1994;108:92-98.[Abstract/Free Full Text]
- Fukuse T., Hirata T., Ueda M., Hitomi S., Wada H. Effects of Euro-Collins, University of Wisconsin, and new extracellular-type trehalase-containing Kyoto solutions in an ex vivo rat lung preservation model. Transplantation 1996;62:1212-1217.[Medline]
- Bando T., Albes J.M., Nusse 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]
- Nakamura T., Hirata T., Fukuse T., Ueda M., Hitomi S., Wada H. Dibutyryl cyclic adenosine monophosphate attenuates lung injury caused by cold preservation and ischemia-reperfusion. J Thorac Cardiovasc Surg 1997;114:635-642.[Abstract/Free Full Text]
- Kawashima M., Bando T., Nakamura T., et al. Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 2000;161:935-943.[Abstract/Free Full Text]
- Fukuse T., Hirata T., Nakamura T., et al. Role of saccharides on lung preservation. Transplantation 1999;68:110-117.[Medline]
- Yoshida H., Okuno H., Kamoto T., et al. Comparison of the effectiveness of ET-Kyoto with Euro-Collins and University of Wisconsin solutions in cold renal storage. Transplantation 2002;74:1231-1236.[Medline]
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Abstract
Introduction
