1. Ex vivo lung model of pig-to-human hyperacute xenograft rejection
Paolo Macchiarini, MDa, Guy-Michel Mazmanian, MDb, Rafael Oriol, MDc, Vincent de Montpreville, MDd, Elisabeth Dulmet, MDd, Soly Fattal, PhDa, Jean-Marie Libert, PhDa, Sylvie Doubine, PhDa, Dominique Nochy, MDe, Robert Rieben, PhDf, Philippe Dartevelle, MDa 
The Journal of Thoracic and Cardiovascular Surgery 
Volume 114, Issue 3, Pages (September 1997)
DOI: /S (97)
Copyright © 1997 Mosby, Inc. Terms and Conditions

2. Fig. 1
The isolated perfused and ventilated ex vivo lung model. Human blood (1) fills the oxygenator cardiotomy reservoir, where it is continuously deoxygenated (93% nitrogen, 5% carbon dioxide, and 2% oxygen) by the neonatal oxygenating system (2), enters through an arterial line into the pulmonary artery, perfuses the lung, and returns to the cardiotomy reservoir through the venous line. A heater (3) warms the blood and lung to 37° C. This last, continuously ventilated by a mechanical ventilator (4) (75% nitrogen, 20% oxygen, and 5% carbon dioxide gas mixture), is suspended in a humidified chamber (5).
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

3. Fig. 2
Hemodynamics (pulmonary vascular resistance, PVR) at baseline (time 0) and at specific time intervals after perfusion of pig lungs with pig or human blood. Data are expressed as mean ± standard deviation (error bars) of the experiments. The difference was statistically significant (p < ). During the time interval between −30 and 0 minutes, the pig lungs were perfused with autogeneic blood to stabilize the perfusion system.
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

4. Fig. 3
Oxygen extraction (AVO2) of pig lungs at specific time intervals after perfusion of pig lungs with pig or human blood. Data are expressed as mean ± standard deviation (error bars) of the experiments; hemoglobin concentrations to calculate the AVO2 were normalized for the observed hematocrit value. The difference was statistically significant (p < ). First 30 minutes as in Fig.1.
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

5. Fig. 4
Histologic studies of pig lungs perfused with human blood. A, Intraarteriolar thrombus (big arrow) of fibrin and platelet; the respiratory epithelium of a small bronchus is indicated by the small arrow . (Original magnification × 360.) B, Venular thrombus of fibrin and platelets in an interalveolar septum. C, Diffuse capillary congestion and alveolar edema and hemorrhage. (Original magnifications × 180).
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

6. Fig. 4
Histologic studies of pig lungs perfused with human blood. A, Intraarteriolar thrombus (big arrow) of fibrin and platelet; the respiratory epithelium of a small bronchus is indicated by the small arrow . (Original magnification × 360.) B, Venular thrombus of fibrin and platelets in an interalveolar septum. C, Diffuse capillary congestion and alveolar edema and hemorrhage. (Original magnifications × 180).
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

7. Fig. 4
Histologic studies of pig lungs perfused with human blood. A, Intraarteriolar thrombus (big arrow) of fibrin and platelet; the respiratory epithelium of a small bronchus is indicated by the small arrow . (Original magnification × 360.) B, Venular thrombus of fibrin and platelets in an interalveolar septum. C, Diffuse capillary congestion and alveolar edema and hemorrhage. (Original magnifications × 180).
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

8. Fig. 5
Wet/dry weight ratio of pig lungs perfused with pig (autogeneic) or human (xenogeneic) blood. Data are expressed as mean ± standard deviation (error bars) of the experiments. The difference was statistically significant (p < 0.01).
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

9. Fig. 6
A, Immunofluorescence with antihuman fibrinogen showing multiple thrombosis in the capillary lumen of the alveolar septa. A thrombus seen longitudinally is indicate by the arrow. B, Immunofluorescence with antihuman C3 showing diffuse deposition of the C3 protein along the alveolar capillaries. (Original magnifications × 200.)
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

10. Fig. 6
A, Immunofluorescence with antihuman fibrinogen showing multiple thrombosis in the capillary lumen of the alveolar septa. A thrombus seen longitudinally is indicate by the arrow. B, Immunofluorescence with antihuman C3 showing diffuse deposition of the C3 protein along the alveolar capillaries. (Original magnifications × 200.)
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

11. Fig. 7
Total complement activity (CH100 in human plasma at baseline (time 0) and at specific time intervals after xenogeneic perfusion of pig lungs with human blood. Data are expressed as mean ± standard deviation (error bars) of the experiments and normalized for the observed hematocrit value. Values below the dotted line are pathologic (< 70 CH100 units/ml.) The CH100 activity dropped from ± 43.2 to 47.7 ± 6.4 units/ml over the study period (p < ). First 30 minutes as in Fig. 1.
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

12. Fig. 8
Hemolysis at baseline (time 0) and at specific time intervals after perfusion of pig lungs with pig or human blood. Data are expressed as mean ± standard deviation (error bars) of the experiments and normalized for the observed hematocrit value. The dotted line represents values normally observed during human cardiopulmonary bypass procedures at our institution (< 150 mg/100ml). The difference was statistically significant (p < ). First 30 minutes as in .Fig. 1.
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

13. Fig. 9
Hematocrit value at baseline (time 0) and at specific time intervals after perfusion of pig lungs with autogeneic or untreated human blood. Data are expressed as mean ± standard deviation (error bars) of the experiments. The difference was statistically significant (p < ). First 30 minutes as in Fig. 1.
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions

14. Fig. 10
Plasma IgM, IgG, and IgA anti-αGal antibodies at baseline (time 0) and at specific time intervals after prefusion of pig lungs with untreated human blood. Data are expressed as mean ± standard deviation (error bars) of the experiments and normalized for the observed hematocrit. IgM (p = 0.003) and IgG (p = 0.03) anti-αGal natural antibodies decreased significantly over the study period, whereas IgA did not reach the threshold of significance (p = 0.08). However, the three human antibodies had a similar kinetic pattern over time, because their decrease was particularly important in the first 30 minutes (p < ) and remained stable thereafter. First 30 minutes as in Fig. 1. OD, Optical density.
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (97) )
Copyright © 1997 Mosby, Inc. Terms and Conditions