Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation.

BACKGROUND: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation. OBJECTIVE: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation. METHODS: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections. RESULTS: Mean lung survival for the experimental group was increased when compared with controls, 240 +/- 0 minutes versus 35.3 +/- 14.5 minutes, respectively, with a P value of less than.01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 +/- 87 mm Hg. L(-1). min(-1), in contrast to the control group (1579 +/- 722 mm Hg. L(-1). min(-1); P <.01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 +/- 1.41 mL. cm(-2) H(2)O and 4.11 +/- 2.84 mL. cm(-2) H(2)O, respectively; P <.01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group. CONCLUSIONS: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation.

The mandibular foramen: an anatomic study and its relevance to the sagittal ramus osteotomy.

The sagittal split ramus osteotomy is the most commonly used procedure to reposition the mandible surgically. Because it is more technically difficult and associated with a higher incidence of complications compared with other mandibular osteotomies, thorough knowledge of the anatomy of the mandibular ramus is a prerequisite. Anatomic measurements related to the mandibular foramen were obtained from 57 formalin-preserved non-Asian hemimandibles. As shown in previous reports, great variability was noted in the position of the mandibular foramen. However, these studies utilized Asian mandibles with a clear discrepancy in key anatomic measurements in comparison with the authors' data. This brings into question the validity of these earlier studies when applying their data to non-Asian groups. The "fade-out" point of the internal oblique ridge was found not to be a reliable anatomic reference for placement of the horizontal osteotomy along the medial ramus. Thus, familiarity with the described relationships of the mandibular foramen will assist in performing properly a sagittal split of the ramus and will reduce the chance for an unfavorable split.