Mark Yeatman, MD, C. William Daggett, MD, Christine L

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Presentation transcript:

Human complement regulatory proteins protect swine lungs from xenogeneic injury Mark Yeatman, MD, C.William Daggett, MD, Christine L. Lau, MD, Guerard W. Byrne, PhD, John S. Logan, PhD, Jeffrey L. Platt, MD, R.Duane Davis, MD The Annals of Thoracic Surgery Volume 67, Issue 3, Pages 769-775 (March 1999) DOI: 10.1016/S0003-4975(99)00049-1

Fig 1 Isolated working lung preparation. Isolated, single swine lungs were perfused with plasma from the reservoir and ventilated by a cannula inserted into the main bronchus. (CO2 = carbon dioxide; FiO2 = fraction of inspired oxygen; PA = pulmonary artery; PIAP = peak inspiratory airway pressure; PV = pulmonary vein; RR = respiratory rate.) The Annals of Thoracic Surgery 1999 67, 769-775DOI: (10.1016/S0003-4975(99)00049-1)

Fig 2 Extracorporeal isolated lung perfusion apparatus. Swine lungs were perfused via the pulmonary artery with baboon blood following cannulation of the host right atrium. Lungs were ventilated by a cannula inserted into the swine trachea. (PAP = pulmonary artery pressure; PAQ = pulmonary artery flow; RA = right atrium. Other abbreviations as in Figure 1.) The Annals of Thoracic Surgery 1999 67, 769-775DOI: (10.1016/S0003-4975(99)00049-1)

Fig 3 Pulmonary vascular resistance (PVR) during perfusion of swine lungs with plasma (A) and baboon blood (B). Perfusion of unmodified swine lungs with human plasma or baboon blood resulted in a several-fold increase in PVR. This increase in PVR was not apparent in the hDAF/hCD59 swine lungs. (SNK = Student- Newman-Keuls method; TW RM ANOVA = two-way repeated measurements analysis of variance.) The Annals of Thoracic Surgery 1999 67, 769-775DOI: (10.1016/S0003-4975(99)00049-1)

Fig 4 Static pulmonary compliance during perfusion of swine lungs with human plasma (A) or baboon blood (B). Perfusion of unmodified swine lungs with human plasma (+ve controls) or baboon blood resulted in a several-fold loss of static pulmonary compliance (SPC). In unmodified swine lungs perfused with human plasma (+ve controls) this was even apparent at only 10 minutes. In contrast, SPC in hDAF/hCD59 swine lungs perfused with human plasma or baboon blood remained relatively constant even after 120 minutes. (SNK = Student-Newman-Keuls method; TW RM ANOVA = two-way repeated measurements analysis of variance.) The Annals of Thoracic Surgery 1999 67, 769-775DOI: (10.1016/S0003-4975(99)00049-1)

Fig 5 Histopathologic abnormalities after 120 minutes of isolated lung perfusion. Heterologous perfusion of swine lungs with human plasma resulted in severe morphologic injury, including alveolar edema and alveolar wall disruption (B and C). Perfusion of unmodified swine lungs with baboon blood resulted in widespread injury characterized by macrovascular thrombus formation, pulmonary capillary congestion, and intraalveolar congestion (E). These abnormalities were not observed in swine lungs perfused autologously (−ve controls) (A) or in the hDAF/hCD59-expressing swine lungs perfused with human plasma (D) or baboon blood (F). (All stained with hematoxylin and eosin.) The Annals of Thoracic Surgery 1999 67, 769-775DOI: (10.1016/S0003-4975(99)00049-1)

Fig 6 Baboon systemic plasma C3a-desArg concentrations during perfusion of unmodified and hDAF/hCD59-expressing swine lungs. After 60 minutes of extracorporeal lung perfusion, baboon C3a-desArg levels increased several-fold in both groups, indicating complement activation. The subsequent return to baseline values in the unmodified swine lung group is consistent with cessation of pulmonary perfusion, whereas the continued elevation of C3a-desArg in the hDAF/hCD59 group indicates that activation of the complement persisted. The Annals of Thoracic Surgery 1999 67, 769-775DOI: (10.1016/S0003-4975(99)00049-1)