Skip to main content
Top
Published in: Respiratory Research 1/2018

Open Access 01-12-2018 | Research

Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study

Authors: Jasmin Steinmeyer, Simon Becker, Murat Avsar, Jawad Salman, Klaus Höffler, Axel Haverich, Gregor Warnecke, Christian Mühlfeld, Matthias Ochs, Anke Schnapper-Isl

Published in: Respiratory Research | Issue 1/2018

Login to get access

Abstract

Background

Ex vivo lung perfusion (EVLP) is used by an increasing number of transplant centres. It is still controversial whether an acellular or cellular (erythrocyte enriched) perfusate is preferable. The aim of this paper was to evaluate whether acellular (aEVLP) or cellular EVLP (cEVLP) preserves functional lung ultrastructure better and to generate a hypothesis regarding possible underlying mechanisms.

Methods

Lungs of 20 pigs were assigned to 4 groups: control, ischaemia (24 h), aEVLP and cEVLP (both EVLP groups: 24 h ischaemia + 12 h EVLP). After experimental procedures, whole lungs were perfusion fixed, samples for light and electron microscopic stereology were taken, and ventilation, diffusion and perfusion related parameters were estimated.

Results

Lung structure was well preserved in all groups. Lungs had less atelectasis and higher air content after EVLP. No significant group differences were found in alveolar septum composition or blood-air barrier thickness. Small amounts of intraalveolar oedema were detected in both EVLP groups but significantly more in aEVLP than in cEVLP.

Conclusions

Both EVLP protocols supported lungs well for up to 12 h and could largely prevent ischaemia ex vivo reperfusion associated lung injury. In both EVLP groups, oedema volume remained below the level of functional relevance. The group difference in oedema formation was possibly due to inferior septal perfusion in aEVLP.
Appendix
Available only for authorised users
Literature
1.
go back to reference Smits JM, Nossent GD, de Vries E, Rahmel A, Meiser B, Strueber M, et al. Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant. J Heart Lung Transplant. 2011;30:22–8.CrossRefPubMed Smits JM, Nossent GD, de Vries E, Rahmel A, Meiser B, Strueber M, et al. Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant. J Heart Lung Transplant. 2011;30:22–8.CrossRefPubMed
2.
go back to reference de Perrot M, Bonser RS, Dark J, Kelly RF, McGiffin D, Menza R, et al. Report of the ISHLT working group on primary lung graft dysfunction part III: donor-related risk factors and markers. J Heart Lung Transplant. 2005;24:1460–7.CrossRefPubMed de Perrot M, Bonser RS, Dark J, Kelly RF, McGiffin D, Menza R, et al. Report of the ISHLT working group on primary lung graft dysfunction part III: donor-related risk factors and markers. J Heart Lung Transplant. 2005;24:1460–7.CrossRefPubMed
3.
go back to reference de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med. 2003;167:490–511.CrossRefPubMed de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med. 2003;167:490–511.CrossRefPubMed
4.
go back to reference Mühlfeld C, Schaefer IM, Becker L, Bussinger C, Vollroth M, Bosch A, et al. Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion. Eur Respir J. 2009;33:625–33.CrossRefPubMed Mühlfeld C, Schaefer IM, Becker L, Bussinger C, Vollroth M, Bosch A, et al. Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion. Eur Respir J. 2009;33:625–33.CrossRefPubMed
5.
go back to reference Knudsen L, Boxler L, Mühlfeld C, Schaefer IM, Becker L, Bussinger C, et al. Lung preservation in experimental ischemia/reperfusion injury and lung transplantation: a comparison of natural and synthetic surfactants. J Heart Lung Transplant. 2012;31:85–93.CrossRefPubMed Knudsen L, Boxler L, Mühlfeld C, Schaefer IM, Becker L, Bussinger C, et al. Lung preservation in experimental ischemia/reperfusion injury and lung transplantation: a comparison of natural and synthetic surfactants. J Heart Lung Transplant. 2012;31:85–93.CrossRefPubMed
6.
go back to reference Gohrbandt B, Sommer SP, Fischer S, Hohlfeld JM, Warnecke G, Haverich A, et al. Iloprost to improve surfactant function in porcine pulmonary grafts stored for twenty-four hours in low-potassium dextran solution. J Thorac Cardiovasc Surg. 2005;129:80–6.CrossRefPubMed Gohrbandt B, Sommer SP, Fischer S, Hohlfeld JM, Warnecke G, Haverich A, et al. Iloprost to improve surfactant function in porcine pulmonary grafts stored for twenty-four hours in low-potassium dextran solution. J Thorac Cardiovasc Surg. 2005;129:80–6.CrossRefPubMed
7.
go back to reference Cypel M, Keshavjee S. The clinical potential of ex vivo lung perfusion. Expert Rev Respir Med. 2012;6:27–35.CrossRefPubMed Cypel M, Keshavjee S. The clinical potential of ex vivo lung perfusion. Expert Rev Respir Med. 2012;6:27–35.CrossRefPubMed
8.
go back to reference Machuca TN, Hsin MK, Ott HC, Chen M, Hwang DM, Cypel M, et al. Injury-specific ex vivo treatment of the donor lung: pulmonary thrombolysis followed by successful lung transplantation. Am J Respir Crit Care Med. 2013;188:878–80.CrossRefPubMed Machuca TN, Hsin MK, Ott HC, Chen M, Hwang DM, Cypel M, et al. Injury-specific ex vivo treatment of the donor lung: pulmonary thrombolysis followed by successful lung transplantation. Am J Respir Crit Care Med. 2013;188:878–80.CrossRefPubMed
9.
go back to reference Cypel M, Liu M, Rubacha M, Yeung JC, Hirayama S, Anraku M, et al. Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med. 2009;1:4ra9.CrossRefPubMed Cypel M, Liu M, Rubacha M, Yeung JC, Hirayama S, Anraku M, et al. Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med. 2009;1:4ra9.CrossRefPubMed
10.
go back to reference Steen S, Ingemansson R, Eriksson L, Pierre L, Algotsson L, Wierup P, et al. First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Ann Thorac Surg. 2007;83:2191–4.CrossRefPubMed Steen S, Ingemansson R, Eriksson L, Pierre L, Algotsson L, Wierup P, et al. First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Ann Thorac Surg. 2007;83:2191–4.CrossRefPubMed
11.
go back to reference Steen S, Liao Q, Wierup PN, Bolys R, Pierre L, Sjoberg T. Transplantation of lungs from non-heart-beating donors after functional assessment ex vivo. Ann Thorac Surg. 2003;76:244–52.CrossRefPubMed Steen S, Liao Q, Wierup PN, Bolys R, Pierre L, Sjoberg T. Transplantation of lungs from non-heart-beating donors after functional assessment ex vivo. Ann Thorac Surg. 2003;76:244–52.CrossRefPubMed
12.
go back to reference Meers CM, Tsagkaropoulos S, Wauters S, Verbeken E, Vanaudenaerde B, Scheers H, et al. A model of ex vivo perfusion of porcine donor lungs injured by gastric aspiration: a step towards pretransplant reconditioning. J Surg Res. 2011;170:e159–67.CrossRefPubMed Meers CM, Tsagkaropoulos S, Wauters S, Verbeken E, Vanaudenaerde B, Scheers H, et al. A model of ex vivo perfusion of porcine donor lungs injured by gastric aspiration: a step towards pretransplant reconditioning. J Surg Res. 2011;170:e159–67.CrossRefPubMed
13.
go back to reference Cypel M, Yeung JC, Hirayama S, Rubacha M, Fischer S, Anraku M, et al. Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant. 2008;27:1319–25.CrossRefPubMed Cypel M, Yeung JC, Hirayama S, Rubacha M, Fischer S, Anraku M, et al. Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant. 2008;27:1319–25.CrossRefPubMed
14.
go back to reference Nilsson T, Gielis JF, Slama A, Hansson C, Wallinder A, Ricksten SE, et al. Comparison of two strategies for ex vivo lung perfusion. J Heart Lung Transplant. 2018;37:292–8.CrossRef Nilsson T, Gielis JF, Slama A, Hansson C, Wallinder A, Ricksten SE, et al. Comparison of two strategies for ex vivo lung perfusion. J Heart Lung Transplant. 2018;37:292–8.CrossRef
15.
go back to reference Becker S, Steinmeyer J, Avsar M, Höffler K, Salman J, Haverich A, et al. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours. Transpl Int. 2016;29:88–97.CrossRefPubMed Becker S, Steinmeyer J, Avsar M, Höffler K, Salman J, Haverich A, et al. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours. Transpl Int. 2016;29:88–97.CrossRefPubMed
16.
go back to reference Roman M, Gjorgjimajkoska O, Neil D, Nair S, Colah S, Parmar J, et al. Comparison between cellular and acellular perfusates for ex vivo lung perfusion in a porcine model. J Heart Lung Transplant. 2015;34:978–87.CrossRefPubMed Roman M, Gjorgjimajkoska O, Neil D, Nair S, Colah S, Parmar J, et al. Comparison between cellular and acellular perfusates for ex vivo lung perfusion in a porcine model. J Heart Lung Transplant. 2015;34:978–87.CrossRefPubMed
17.
go back to reference Loor G, Howard BT, Spratt JR, Mattison LM, Panoskaltsis-Mortari A, Brown RZ, et al. Prolonged EVLP using OCS lung: cellular and acellular Perfusates. Transplantation. 2017;101:2303–11.CrossRefPubMedPubMedCentral Loor G, Howard BT, Spratt JR, Mattison LM, Panoskaltsis-Mortari A, Brown RZ, et al. Prolonged EVLP using OCS lung: cellular and acellular Perfusates. Transplantation. 2017;101:2303–11.CrossRefPubMedPubMedCentral
18.
go back to reference Oczenski W (2017) Atmen - Atemhilfen. 10 edn. Thieme, Stuttgart. Oczenski W (2017) Atmen - Atemhilfen. 10 edn. Thieme, Stuttgart.
19.
go back to reference Ochs M, Mühlfeld C. Quantitative microscopy of the lung: a problem-based approach. Part 1: basic principles of lung stereology. Am J Physiol Lung Cell Mol Physiol. 2013;305:L15–22.CrossRefPubMed Ochs M, Mühlfeld C. Quantitative microscopy of the lung: a problem-based approach. Part 1: basic principles of lung stereology. Am J Physiol Lung Cell Mol Physiol. 2013;305:L15–22.CrossRefPubMed
20.
go back to reference Hsia CC, Hyde DM, Ochs M, Weibel ER. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010;181:394–418.CrossRefPubMedPubMedCentral Hsia CC, Hyde DM, Ochs M, Weibel ER. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010;181:394–418.CrossRefPubMedPubMedCentral
21.
go back to reference Michel RP, Cruz-Orive LM. Application of the Cavalieri principle and vertical sections method to lung: estimation of volume and pleural surface area. J Microsc. 1988;150:117–36.CrossRefPubMed Michel RP, Cruz-Orive LM. Application of the Cavalieri principle and vertical sections method to lung: estimation of volume and pleural surface area. J Microsc. 1988;150:117–36.CrossRefPubMed
22.
go back to reference Gundersen HJ, Jensen EB. The efficiency of systematic sampling in stereology and its prediction. J Microsc. 1987;147:229–63.CrossRefPubMed Gundersen HJ, Jensen EB. The efficiency of systematic sampling in stereology and its prediction. J Microsc. 1987;147:229–63.CrossRefPubMed
23.
go back to reference Tschanz SA, Burri PH, Weibel ER. A simple tool for stereological assessment of digital images: the STEPanizer. J Microsc. 2011;243:47–59.CrossRefPubMed Tschanz SA, Burri PH, Weibel ER. A simple tool for stereological assessment of digital images: the STEPanizer. J Microsc. 2011;243:47–59.CrossRefPubMed
24.
go back to reference Munshi L, Keshavjee S, Cypel M. Donor management and lung preservation for lung transplantation. Lancet Respir Med. 2013;1:318–28.CrossRefPubMed Munshi L, Keshavjee S, Cypel M. Donor management and lung preservation for lung transplantation. Lancet Respir Med. 2013;1:318–28.CrossRefPubMed
25.
go back to reference Thabut G, Mal H, Cerrina J, Dartevelle P, Dromer C, Velly JF, et al. Graft ischemic time and outcome of lung transplantation: a multicenter analysis. Am J Respir Crit Care Med. 2005;171:786–91.CrossRefPubMed Thabut G, Mal H, Cerrina J, Dartevelle P, Dromer C, Velly JF, et al. Graft ischemic time and outcome of lung transplantation: a multicenter analysis. Am J Respir Crit Care Med. 2005;171:786–91.CrossRefPubMed
26.
go back to reference Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, et al. the registry of the International Society for Heart and Lung Transplantation: thirty-fourth adult lung and heart-lung transplantation Report-2017; focus theme: allograft ischemic time. J Heart Lung Transplant. 2017;36:1047–59.CrossRefPubMed Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, et al. the registry of the International Society for Heart and Lung Transplantation: thirty-fourth adult lung and heart-lung transplantation Report-2017; focus theme: allograft ischemic time. J Heart Lung Transplant. 2017;36:1047–59.CrossRefPubMed
27.
go back to reference Fischer S, Maclean AA, Liu M, Cardella JA, Slutsky AS, Suga M, et al. Dynamic changes in apoptotic and necrotic cell death correlate with severity of ischemia-reperfusion injury in lung transplantation. Am J Respir Crit Care Med. 2000;162:1932–9.CrossRefPubMed Fischer S, Maclean AA, Liu M, Cardella JA, Slutsky AS, Suga M, et al. Dynamic changes in apoptotic and necrotic cell death correlate with severity of ischemia-reperfusion injury in lung transplantation. Am J Respir Crit Care Med. 2000;162:1932–9.CrossRefPubMed
28.
go back to reference Quadri SM, Segall L, de Perrot M, Han B, Edwards V, Jones N, et al. Caspase inhibition improves ischemia-reperfusion injury after lung transplantation. Am J Transplant. 2005;5:292–9.CrossRefPubMed Quadri SM, Segall L, de Perrot M, Han B, Edwards V, Jones N, et al. Caspase inhibition improves ischemia-reperfusion injury after lung transplantation. Am J Transplant. 2005;5:292–9.CrossRefPubMed
30.
go back to reference Cypel M, Yeung JC, Machuca T, Chen M, Singer LG, Yasufuku K, et al. Experience with the first 50 ex vivo lung perfusions in clinical transplantation. J Thorac Cardiovasc Surg. 2012;144:1200–6.CrossRefPubMed Cypel M, Yeung JC, Machuca T, Chen M, Singer LG, Yasufuku K, et al. Experience with the first 50 ex vivo lung perfusions in clinical transplantation. J Thorac Cardiovasc Surg. 2012;144:1200–6.CrossRefPubMed
31.
go back to reference Warnecke G, Moradiellos J, Tudorache I, Kuhn C, Avsar M, Wiegmann B, et al. Normothermic perfusion of donor lungs for preservation and assessment with the organ care system lung before bilateral transplantation: a pilot study of 12 patients. Lancet. 2012;380:1851–8.CrossRefPubMed Warnecke G, Moradiellos J, Tudorache I, Kuhn C, Avsar M, Wiegmann B, et al. Normothermic perfusion of donor lungs for preservation and assessment with the organ care system lung before bilateral transplantation: a pilot study of 12 patients. Lancet. 2012;380:1851–8.CrossRefPubMed
32.
go back to reference Wallinder A, Ricksten SE, Silverborn M, Hansson C, Riise GC, Liden H, et al. Early results in transplantation of initially rejected donor lungs after ex vivo lung perfusion: a case-control study. Eur J Cardiothorac Surg. 2014;45:40–4.CrossRefPubMed Wallinder A, Ricksten SE, Silverborn M, Hansson C, Riise GC, Liden H, et al. Early results in transplantation of initially rejected donor lungs after ex vivo lung perfusion: a case-control study. Eur J Cardiothorac Surg. 2014;45:40–4.CrossRefPubMed
33.
go back to reference Spratt JR, Mattison LM, Iaizzo PA, Brown RZ, Helms H, Iles TL, et al. An experimental study of the recovery of injured porcine lungs with prolonged normothermic cellular ex vivo lung perfusion following donation after circulatory death. Transpl Int. 2017;30:932–44.CrossRefPubMed Spratt JR, Mattison LM, Iaizzo PA, Brown RZ, Helms H, Iles TL, et al. An experimental study of the recovery of injured porcine lungs with prolonged normothermic cellular ex vivo lung perfusion following donation after circulatory death. Transpl Int. 2017;30:932–44.CrossRefPubMed
34.
go back to reference den Hengst WA, Gielis JF, Lin JY, Van Schil PE, De Windt LJ, Moens AL. Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am J Physiol Heart Circ Physiol. 2010;299:H1283–99.CrossRef den Hengst WA, Gielis JF, Lin JY, Van Schil PE, De Windt LJ, Moens AL. Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am J Physiol Heart Circ Physiol. 2010;299:H1283–99.CrossRef
36.
go back to reference Khimenko PL, Taylor AE. Segmental microvascular permeability in ischemia-reperfusion injury in rat lung. Am J Phys. 1999;276:L958–60. Khimenko PL, Taylor AE. Segmental microvascular permeability in ischemia-reperfusion injury in rat lung. Am J Phys. 1999;276:L958–60.
37.
go back to reference Zhao M, Fernandez LG, Doctor A, Sharma AK, Zarbock A, Tribble CG, et al. Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2006;291:L1018–26.CrossRefPubMed Zhao M, Fernandez LG, Doctor A, Sharma AK, Zarbock A, Tribble CG, et al. Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2006;291:L1018–26.CrossRefPubMed
38.
go back to reference Sharma AK, Linden J, Kron IL, Laubach VE. Protection from pulmonary ischemia-reperfusion injury by adenosine A2A receptor activation. Respir Res. 2009;10:58.CrossRefPubMedPubMedCentral Sharma AK, Linden J, Kron IL, Laubach VE. Protection from pulmonary ischemia-reperfusion injury by adenosine A2A receptor activation. Respir Res. 2009;10:58.CrossRefPubMedPubMedCentral
39.
go back to reference Fiser SM, Tribble CG, Long SM, Kaza AK, Cope JT, Laubach VE, et al. Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response. J Thorac Cardiovasc Surg. 2001;121:1069–75.CrossRefPubMed Fiser SM, Tribble CG, Long SM, Kaza AK, Cope JT, Laubach VE, et al. Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response. J Thorac Cardiovasc Surg. 2001;121:1069–75.CrossRefPubMed
40.
go back to reference Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D. Report of the ISHLT working group on primary lung graft dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005;24:1454–9.CrossRefPubMed Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D. Report of the ISHLT working group on primary lung graft dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005;24:1454–9.CrossRefPubMed
41.
go back to reference Fischer S, Cassivi SD, Xavier AM, Cardella JA, Cutz E, Edwards V, et al. Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation. Ann Surg. 2000;231:424–31.CrossRefPubMedPubMedCentral Fischer S, Cassivi SD, Xavier AM, Cardella JA, Cutz E, Edwards V, et al. Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation. Ann Surg. 2000;231:424–31.CrossRefPubMedPubMedCentral
42.
go back to reference Ochs M, O'Brodovich H. The structural and physiologic basis of respiratory disease. In: Wilmott RW, Boat TF, Bush A, Chernick V, Deterding RR, Ratjen F, editors. Kendig and Chernick's disorders of the respiratory tract in children. 8th ed. Philadelphia: Elsevier; 2012. p. 35–74.CrossRef Ochs M, O'Brodovich H. The structural and physiologic basis of respiratory disease. In: Wilmott RW, Boat TF, Bush A, Chernick V, Deterding RR, Ratjen F, editors. Kendig and Chernick's disorders of the respiratory tract in children. 8th ed. Philadelphia: Elsevier; 2012. p. 35–74.CrossRef
43.
go back to reference Schnapper A, Ochs M. Lung transplantation and the blood-gas barrier. In: Makanya A, editor. The vertebrate blood-gas barrier in health and disease - structure, development and remodeling. Heidelberg: Springer; 2015. p. 189–220.CrossRef Schnapper A, Ochs M. Lung transplantation and the blood-gas barrier. In: Makanya A, editor. The vertebrate blood-gas barrier in health and disease - structure, development and remodeling. Heidelberg: Springer; 2015. p. 189–220.CrossRef
44.
go back to reference Gehr P, Bachofen M, Weibel ER. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol. 1978;32:121–40.CrossRefPubMed Gehr P, Bachofen M, Weibel ER. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol. 1978;32:121–40.CrossRefPubMed
45.
go back to reference Schnapper A, Christmann A, Knudsen L, Rahmanian P, Choi YH, Zeriouh M, et al. Stereological assessment of the blood-air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non-heart-beating donor model for lung transplantation. J Anat. 2018;232:283–95.CrossRefPubMed Schnapper A, Christmann A, Knudsen L, Rahmanian P, Choi YH, Zeriouh M, et al. Stereological assessment of the blood-air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non-heart-beating donor model for lung transplantation. J Anat. 2018;232:283–95.CrossRefPubMed
46.
go back to reference Winkler GC, Cheville NF. Morphometry of postnatal development in the porcine lung. Anat Rec. 1985;211:427–33.CrossRefPubMed Winkler GC, Cheville NF. Morphometry of postnatal development in the porcine lung. Anat Rec. 1985;211:427–33.CrossRefPubMed
47.
go back to reference Ochs M. Stereological analysis of acute lung injury. Eur Respir Rev. 2006;15:115–21.CrossRef Ochs M. Stereological analysis of acute lung injury. Eur Respir Rev. 2006;15:115–21.CrossRef
48.
go back to reference Fehrenbach A, Fehrenbach H, Wittwer T, Ochs M, Wahlers T, Richter J. Evaluation of pulmonary edema: stereological versus gravimetrical analysis. Eur Surg Res. 2001;33:270–8.CrossRefPubMed Fehrenbach A, Fehrenbach H, Wittwer T, Ochs M, Wahlers T, Richter J. Evaluation of pulmonary edema: stereological versus gravimetrical analysis. Eur Surg Res. 2001;33:270–8.CrossRefPubMed
49.
go back to reference Kunzelmann K, Thews O. Lungenatmung. In: Schmidt RF, Lang F, Heckmann M, editors. Physiologie des Menschen: mit Pathophysiologie. 31 ed. Berlin, Heidelberg: Springer; 2011. p. 697–723.CrossRef Kunzelmann K, Thews O. Lungenatmung. In: Schmidt RF, Lang F, Heckmann M, editors. Physiologie des Menschen: mit Pathophysiologie. 31 ed. Berlin, Heidelberg: Springer; 2011. p. 697–723.CrossRef
50.
go back to reference Murray JF, Karp RB, Nadel JA. Viscosity effects on pressure-flow relations and vascular resistance in dogs' lungs. J Appl Physiol. 1969;27:336–41.CrossRefPubMed Murray JF, Karp RB, Nadel JA. Viscosity effects on pressure-flow relations and vascular resistance in dogs' lungs. J Appl Physiol. 1969;27:336–41.CrossRefPubMed
51.
go back to reference Nihill MR, McNamara DG, Vick RL. The effects of increased blood viscosity on pulmonary vascular resistance. Am Heart J. 1976;92:65–72.CrossRefPubMed Nihill MR, McNamara DG, Vick RL. The effects of increased blood viscosity on pulmonary vascular resistance. Am Heart J. 1976;92:65–72.CrossRefPubMed
52.
go back to reference Jelkmann W. Blut. In: Schmidt RF, Lang F, Heckmann M, editors. Physiologie des Menschen. 31 ed. Heidelberg: Springer; 2010. p. 477–502.CrossRef Jelkmann W. Blut. In: Schmidt RF, Lang F, Heckmann M, editors. Physiologie des Menschen. 31 ed. Heidelberg: Springer; 2010. p. 477–502.CrossRef
53.
go back to reference Brandes R, Busse R. Kreislauf. In: Schmidt RF, Lang F, Heckmann M, editors. Physiologie des Menschen. 31 ed. Heidelberg: Springer; 2010. p. 572–626.CrossRef Brandes R, Busse R. Kreislauf. In: Schmidt RF, Lang F, Heckmann M, editors. Physiologie des Menschen. 31 ed. Heidelberg: Springer; 2010. p. 572–626.CrossRef
54.
go back to reference Aboelnazar NS, Himmat S, Hatami S, White CW, Burhani MS, Dromparis P, et al. Negative pressure ventilation decreases inflammation and lung edema during normothermic ex-vivo lung perfusion. J Heart Lung Transplant. 2018;37:520–30.CrossRefPubMed Aboelnazar NS, Himmat S, Hatami S, White CW, Burhani MS, Dromparis P, et al. Negative pressure ventilation decreases inflammation and lung edema during normothermic ex-vivo lung perfusion. J Heart Lung Transplant. 2018;37:520–30.CrossRefPubMed
56.
go back to reference Weibel ER, Hsia CC, Ochs M. How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol. 2007;102:459–67.CrossRefPubMed Weibel ER, Hsia CC, Ochs M. How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol. 2007;102:459–67.CrossRefPubMed
57.
go back to reference Mühlfeld C, Ochs M. Quantitative microscopy of the lung: a problem-based approach. Part 2: stereological parameters and study designs in various diseases of the respiratory tract. Am J Physiol Lung Cell Mol Physiol. 2013;305:L205–21.CrossRefPubMed Mühlfeld C, Ochs M. Quantitative microscopy of the lung: a problem-based approach. Part 2: stereological parameters and study designs in various diseases of the respiratory tract. Am J Physiol Lung Cell Mol Physiol. 2013;305:L205–21.CrossRefPubMed
58.
go back to reference Stammberger U, Gaspert A, Hillinger S, Vogt P, Odermatt B, Weder W, et al. Apoptosis induced by ischemia and reperfusion in experimental lung transplantation. Ann Thorac Surg. 2000;69:1532–6.CrossRefPubMed Stammberger U, Gaspert A, Hillinger S, Vogt P, Odermatt B, Weder W, et al. Apoptosis induced by ischemia and reperfusion in experimental lung transplantation. Ann Thorac Surg. 2000;69:1532–6.CrossRefPubMed
59.
go back to reference Van Raemdonck D, Neyrinck A, Verleden GM, Dupont L, Coosemans W, Decaluwe H, et al. Lung donor selection and management. Proc Am Thorac Soc. 2009;6:28–38.CrossRefPubMed Van Raemdonck D, Neyrinck A, Verleden GM, Dupont L, Coosemans W, Decaluwe H, et al. Lung donor selection and management. Proc Am Thorac Soc. 2009;6:28–38.CrossRefPubMed
Metadata
Title
Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study
Authors
Jasmin Steinmeyer
Simon Becker
Murat Avsar
Jawad Salman
Klaus Höffler
Axel Haverich
Gregor Warnecke
Christian Mühlfeld
Matthias Ochs
Anke Schnapper-Isl
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2018
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-018-0942-5

Other articles of this Issue 1/2018

Respiratory Research 1/2018 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.