Cryotechnology in lung and heart-lung transplantation
M. T. BekovI. V. PashkovН. П. МожейкоР. А. ЛатыповD. O. OleshkevichKirill SmirnovE. F. ShigaevYa. S. YakuninS. V. Gautier
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Bronchial complications, along with development and progression of chronic dysfunction on the background of chronic rejection, are factors that reduce the quality and life of lung and heart-lung recipients. They also increase the frequency of hospitalizations. Application of cryotechnology is based on the contact effect of extremely low temperatures on organs and tissues using a cryoprobe. This article demonstrates the experience of using cryotechnology in the diagnosis and treatment of complications in lung and heart-lung recipients.Keywords:
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The right lung consists of the upper, middle, accessory and lower lobes. In the left lung, the upper and accessory lobes are lost. The middle and lower lobes are united to form one lobe. The left lung is smaller than the right lung.
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In the article, following the results of complex methods (anatomic, histologic, organometric, histometric and statistical) researches are shown the features of morphological structure and morphometric parameters of the lungs of mature rabbits. It was found out, that macro- and microscopic architecture of rabbit lungs has similar histoarchitectonics, inherent in other species of farm animals of the class "mammals" and the characteristic features of morphological structures. Lungs in clinically healthy rabbits structurally reflect the shape of thoracic cavity and gradually expand ventrally. Subsequent to the results of performed organometry, the absolute lung mass of mature rabbits is 18,05±1,32 g, relative 0,624±0,013 %. The Right and left rabbit lungs are surrounded by pleural sacs (right and left): in rabbits pleural spaces of the right and left lungs are not connected. According to morphological and organometric investigations the rabbit lungs are relating to VIII type – the reduction of the superior lobe of left lung is observed, consequently right lung is more developed than left ( the length of right lung is 6,40±0,45 mm, the width – 3,54±0,30 mm, the thickness – 3,28±0,30 mm; the length of left lung is 6,84±0,40 mm; 4,18±0,30 mm and 1,52±0,30 mm relatively) and the coefficient of lung asymmetry (right to left) according to their absolute mass is 1.16. Although, rabbit lungs have dilatated base and superior. Right lung divides into four lobes – cranial (the superior), cardio, diaphragmatic and ancilla, left one divides into three lobes – the reduced superior, cardio and diaphragmatic. Histoarchitecture of lungs is formed by lobes of the lungs, that are separated by connective tissue, which contains blood and lymphatic vessels. Lung parenchyma is created by airways and respiratory divisions that blood vessels accompany to. Respiratory lung parenchyma is formed by respiratory bronchioles, alveolar ducts and alveolar saccules, in which walls the alveolus are located and shape the alveolar tree. According to the analysis of histometry results, respiratory (breathing) lobe of lungs of experimental rabbits is 52,3± 0,62 %, connective tissue base – 69,6±1,27 %, and the average volume of alveolus (small, middle and big) is equal to 42,3±4,35 thousand mkm3.
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Left anterior, lateral, and posterior views on 50 consecutive RES-lung scams were examined. Normal patients had continuity of activity between the left lung and the spleen on all three views. Patients with subphrenic abscess or large left pleural effusions showed no continuity between lung and spleen activity on any view, while other abnormalities, most commonly cardiomegaly, accounted for lack of lung-spleen continuity on the anterior view only. It is suggested that in all combined RES-lung studies, the left side be examined as well as the right for abnormalities adjacent to the left diaphragm.
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Central MessageA novel technique of "inverted" rat lung transplant with left donor lung rotated 180° and implanted to recipient contralateral/right chest provides a promising model for future experiments.See Article page 429.Animal models have been a cornerstone in the development of lung transplantation. The first long-term clinical successes with heart–lung transplant at Stanford in 1981 and isolated lung transplantation by the Toronto group in 1983 were built on preceding decades of animal model research.1Venuta F. Van Raemdonck D. History of lung transplantation.J Thorac Dis. 2017; 9: 5458-5471Crossref PubMed Scopus (31) Google Scholar,2Bribriesco A.C. Li W. Nava R.G. Spahn J.H. Kreisel D. Experimental models of lung transplantation.Front Biosci (Elite Ed). 2013; 5: 266-272Crossref PubMed Google ScholarEarly animal experiments were aimed at developing surgical techniques, such as en bloc double-lung transplantation in canine models.3Dark J.H. Patterson G.A. Al-Jilaihawi A.N. Hsu H. Egan T. Cooper J.D. Experimental en bloc double-lung transplantation.Ann Thorac Surg. 1986; 42: 394-398Abstract Full Text PDF PubMed Scopus (36) Google Scholar Presently, more cost-effective and reproducible rodent models are the predominant platform for mechanistic experiments in exploring critical items such as primary graft dysfunction, acute rejection, and chronic lung allograft dysfunction. Compared with other lung transplant models such as hilar occlusion or tracheal transplant, orthotopic left lung transplantation (OLLT) is a robust and versatile experimental technique that most closely simulates the human situation.4Lama V.N. Belperio J.A. Christie J.D. El-Chemaly S. Fishbein M.C. Gelman A.E. et al.Models of lung transplant research: a consensus statement from the National Heart, Lung, and Blood Institute workshop.JCI Insight. 2017; 2: e93121Crossref PubMed Scopus (37) Google Scholar, 5Okazaki M. Krupnick A.S. Kornfeld C.G. Lai J.M. Ritter J.H. Richardson S.B. et al.A mouse model of orthotopic vascularized aerated lung transplantation.Am J Transplant. 2007; 7: 1672-1679Crossref PubMed Scopus (126) Google Scholar, 6Lin X. Li W. Lai J. Okazaki M. Sugimoto S. Yamamoto S. et al.Five-year update on the mouse model of orthotopic lung transplantation: scientific uses, tricks of the trade, and tips for success.J Thorac Dis. 2012; 4: 247-258PubMed Google Scholar However, there are notable limitations to the OLLT model. Anatomically, the rodent left lung consists of only 1 lobe compared with the 5 lobes of the right such that the contribution from the transplanted left lung can be completely masked by the native right lung. This negates the important experimental end point of animal survival as a marker of allograft status. Orthotopic right lung transplant has been described but is technically more challenging, thereby hindering widespread adoption.7Li W. Sugimoto S. Lai J. Patterson G.A. Gelman A.E. Krupnick A.S. et al.Orthotopic vascularized right lung transplantation in the mouse.J Thorac Cardiovasc Surg. 2010; 139: 1637-1643Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar To date, orthotopic bilateral lung transplant (either en bloc or sequential) in the rodent has not been achieved.In this issue of JTCVS Open, Huang and colleagues8Huang H. Yan H.-J. Zheng X.-Y. Wang J.J. Tang H.T. Li C.H. et al.Right lung transplantation with a left-to-right inverted anastomosis in a rat model.J Thorac Cardiovasc Surg Open. 2022; 10: 429-439Scopus (1) Google Scholar turn the tables of the animal model-to-human paradigm with a technical report of a novel "inverted" rat single-lung transplant procedure inspired by the Kyoto group's successful human lobar lung transplantation of a right lower lobe implanted into the left chest.9Chen F. Miyamoto E. Takemoto M. Minakata K. Yamada T. Sato M. et al.Right and left inverted lobar lung transplantation.Am J Transplant. 2015; 15: 1716-1721Crossref PubMed Scopus (22) Google Scholar Elegantly described and depicted in the accompanying video, a rat donor left lung is rotated 180° and transplanted to the recipient's right chest using a standard 3-cuff anastomotic technique (inverted left-right transplant, IL-RT). This innovative model leverages the anatomic size discrepancy between the smaller left lung versus larger right chest cavity, allowing for a technically simpler and reproducible procedure compared with other techniques of right lung transplant.In 10 IL-RT procedures, the authors report 100% intraoperative technical success with 90% survival to the planned end point of 7 days. Total procedure time was comparable between IL-RT and 10 standard/control OLLT animals (58.2 vs 56.6 minutes, P = not significant). Important experimental details to note were the differences in cold and warm ischemic times between the IL-RT and OLLT groups. When compared with the OLLT, the IL-RT group had shorter cold ischemia time (14 minutes vs 25.5 minutes, P < .001) but longer warm ischemia time (19.8 vs 13.7 minutes, P < .001). It is unclear whether these small absolute differences in ischemic times will have meaningful biologic effect, but these and other facets of the IL-RT model will likely be explored and potentially gainfully used in forthcoming experiments.The authors are to be commended for their impressive technical achievement. As with all animal models, there are limitations to be addressed but, overall, this innovative procedure represents an exciting new tool for future research in lung transplantation. A novel technique of "inverted" rat lung transplant with left donor lung rotated 180° and implanted to recipient contralateral/right chest provides a promising model for future experiments. A novel technique of "inverted" rat lung transplant with left donor lung rotated 180° and implanted to recipient contralateral/right chest provides a promising model for future experiments. See Article page 429. See Article page 429. Animal models have been a cornerstone in the development of lung transplantation. The first long-term clinical successes with heart–lung transplant at Stanford in 1981 and isolated lung transplantation by the Toronto group in 1983 were built on preceding decades of animal model research.1Venuta F. Van Raemdonck D. History of lung transplantation.J Thorac Dis. 2017; 9: 5458-5471Crossref PubMed Scopus (31) Google Scholar,2Bribriesco A.C. Li W. Nava R.G. Spahn J.H. Kreisel D. Experimental models of lung transplantation.Front Biosci (Elite Ed). 2013; 5: 266-272Crossref PubMed Google Scholar Early animal experiments were aimed at developing surgical techniques, such as en bloc double-lung transplantation in canine models.3Dark J.H. Patterson G.A. Al-Jilaihawi A.N. Hsu H. Egan T. Cooper J.D. Experimental en bloc double-lung transplantation.Ann Thorac Surg. 1986; 42: 394-398Abstract Full Text PDF PubMed Scopus (36) Google Scholar Presently, more cost-effective and reproducible rodent models are the predominant platform for mechanistic experiments in exploring critical items such as primary graft dysfunction, acute rejection, and chronic lung allograft dysfunction. Compared with other lung transplant models such as hilar occlusion or tracheal transplant, orthotopic left lung transplantation (OLLT) is a robust and versatile experimental technique that most closely simulates the human situation.4Lama V.N. Belperio J.A. Christie J.D. El-Chemaly S. Fishbein M.C. Gelman A.E. et al.Models of lung transplant research: a consensus statement from the National Heart, Lung, and Blood Institute workshop.JCI Insight. 2017; 2: e93121Crossref PubMed Scopus (37) Google Scholar, 5Okazaki M. Krupnick A.S. Kornfeld C.G. Lai J.M. Ritter J.H. Richardson S.B. et al.A mouse model of orthotopic vascularized aerated lung transplantation.Am J Transplant. 2007; 7: 1672-1679Crossref PubMed Scopus (126) Google Scholar, 6Lin X. Li W. Lai J. Okazaki M. Sugimoto S. Yamamoto S. et al.Five-year update on the mouse model of orthotopic lung transplantation: scientific uses, tricks of the trade, and tips for success.J Thorac Dis. 2012; 4: 247-258PubMed Google Scholar However, there are notable limitations to the OLLT model. Anatomically, the rodent left lung consists of only 1 lobe compared with the 5 lobes of the right such that the contribution from the transplanted left lung can be completely masked by the native right lung. This negates the important experimental end point of animal survival as a marker of allograft status. Orthotopic right lung transplant has been described but is technically more challenging, thereby hindering widespread adoption.7Li W. Sugimoto S. Lai J. Patterson G.A. Gelman A.E. Krupnick A.S. et al.Orthotopic vascularized right lung transplantation in the mouse.J Thorac Cardiovasc Surg. 2010; 139: 1637-1643Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar To date, orthotopic bilateral lung transplant (either en bloc or sequential) in the rodent has not been achieved. In this issue of JTCVS Open, Huang and colleagues8Huang H. Yan H.-J. Zheng X.-Y. Wang J.J. Tang H.T. Li C.H. et al.Right lung transplantation with a left-to-right inverted anastomosis in a rat model.J Thorac Cardiovasc Surg Open. 2022; 10: 429-439Scopus (1) Google Scholar turn the tables of the animal model-to-human paradigm with a technical report of a novel "inverted" rat single-lung transplant procedure inspired by the Kyoto group's successful human lobar lung transplantation of a right lower lobe implanted into the left chest.9Chen F. Miyamoto E. Takemoto M. Minakata K. Yamada T. Sato M. et al.Right and left inverted lobar lung transplantation.Am J Transplant. 2015; 15: 1716-1721Crossref PubMed Scopus (22) Google Scholar Elegantly described and depicted in the accompanying video, a rat donor left lung is rotated 180° and transplanted to the recipient's right chest using a standard 3-cuff anastomotic technique (inverted left-right transplant, IL-RT). This innovative model leverages the anatomic size discrepancy between the smaller left lung versus larger right chest cavity, allowing for a technically simpler and reproducible procedure compared with other techniques of right lung transplant. In 10 IL-RT procedures, the authors report 100% intraoperative technical success with 90% survival to the planned end point of 7 days. Total procedure time was comparable between IL-RT and 10 standard/control OLLT animals (58.2 vs 56.6 minutes, P = not significant). Important experimental details to note were the differences in cold and warm ischemic times between the IL-RT and OLLT groups. When compared with the OLLT, the IL-RT group had shorter cold ischemia time (14 minutes vs 25.5 minutes, P < .001) but longer warm ischemia time (19.8 vs 13.7 minutes, P < .001). It is unclear whether these small absolute differences in ischemic times will have meaningful biologic effect, but these and other facets of the IL-RT model will likely be explored and potentially gainfully used in forthcoming experiments. The authors are to be commended for their impressive technical achievement. As with all animal models, there are limitations to be addressed but, overall, this innovative procedure represents an exciting new tool for future research in lung transplantation. Right lung transplantation with a left-to-right inverted anastomosis in a rat modelJTCVS OpenVol. 10PreviewRight lung transplantation in rats has been attempted occasionally, but the technical complexity makes it challenging to apply routinely. Additionally, basic research on inverted lobar lung transplantation is scarce because of the lack of a cost-effective experimental model. We first reported right lung transplantation in a rat model using left-to-right inverted anastomosis to imitate the principle of clinically inverted lung transplantation. Full-Text PDF Open Access
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We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT).We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group).The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group.EVL-CT may predict the outcome of the early phase after lung transplantation.
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Purpese: Lung transplantation is now accepted as an effective therapy for end-stage pulmonary vascular and parenchymal diseases. Rejection is a major impediment to long-term survival of lung transplant recipients. Lung allograft rejection has been studied in various animal models. To study the immunological mechanism of its rejection the studies on lung allograft rejection must be performed in inbred animals such as mice or rats, However, it is very delicate and difficult to transplant the lung in small inbred animals, especially in mice. The technical difficulty hampered the investigations of lung allograft rejection. Methods: This study introduced the new lung transplantation technique in mice for immunological study, subcutaneous lung tissue transplantation, in which the piece of lung tissue with 1-1.5 mm thickness was introduced subcutaneously through incision site on flank and transplanted to subcutaneous site of shoulder of mouse. Histological changes were followed up in transplanted lung tissues for 18 to 21 days. Lung tissues from CBA mice or Balb/c mice were subcutaneously transplanted to Balb/c mice in experimental or control group respectively. Results: Histological changes in the grafts of experimental groups could be divided into 4 phases, inflammatory, immunological, necrotic and fibrotic phase, Immunological or necrotic phase in this study correlated with grade 1-3 or grade 3-4 of acute lung rejection classified by the Lung Rejection Study Group. Conclusion: It is concluded that the subcutaneous lung tissue transplantation can be a technique for immunological study on acute lung allograft rejection in mice.
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Heart-Lung Transplantation
Immunosuppression
Organ procurement
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