David D. Yuh

Perinatal induction of immunotolerance to cardiac and pulmonary allografts

OBJECTIVES Tolerance appears to be more easily induced in the fetus before full immunocompetence is established, but elucidation of this process is needed. A model of perinatal tolerance induction to neonatal skin allografts followed by cardiac and pulmonary allografts is described. METHODS Sixty Lewis (RT11) rat fetuses were inoculated intraperitoneally at 18 days gestation with 1 x 10(7) ACI (RT1a) rat fetal liver cells (group I); 20 Lewis fetuses were inoculated with 2 x 10(7) ACI fetal liver cells (Group II). control groups consisted of Lewis fetuses inoculated with saline solution (n = 25, group III) and fetuses that were not inoculated (n = 25, group IV). Twenty-five of the 50 surviving group I rats received ACI skin (< 24 hours old) and heart (8 to 10 weeks old) allografts (group IA); the remaining 25 rats received only ACI heart grafts (group IB). Groups II, III, and IV received ACI skin and cardiac allografts. Recipients tolerant to both skin and cardiac grafts received orthotopic ACI lung grafts and third-party skin grafts. Tolerance was indicated by graft survival for more than 100 days. Limiting dilution and flow cytometric analyses were performed. RESULTS Abortion rates in groups I, II, III, and IV were 17% (10/60), 65% (13/20), 8% (2/25), and 4% (1/25), respectively. Specific tolerance to skin, cardiac, and lung allografts was observed in seven of 25 group IA recipients (28%) and seven of seven group II recipients (100%) compared with no tolerance in any group IB, III, or IV recipients (p = 0.03, chi 2 test). A 100-fold reduction of precursor cytotoxic T lymphocytes and significant splenocyte and bone marrow chimerism in tolerant versus nontolerant rats were noted (p = 0.0001, Students t test). CONCLUSIONS Using donor-strain fetal liver cells and neonatal skin grafts, we achieved higher frequencies of tolerance to solid organ grafts in adulthood with lower cell inocula and abortion rates than previously described. Chimerism and depressed precursor cytotoxic T lymphocyte frequencies in tolerant recipients suggest that hematopoietic stem cell engraftment and clonal deletion/anergy are involved in induction of perinatal tolerance.

What Lies Beneath (the Mitral Annulus): The Geometric Implications of Restrictive Annuloplasty

From the Department of Surgery, Stamford Hospital, Stamford, Conn. Disclosures: Author has nothing to disclose with regard to commercial support. Received for publication March 1, 2018; accepted for publication March 6, 2018. Address for reprints: David D. Yuh, MD, FACS, FACC, Department of Surgery, Stamford Hospital, Stamford, CT 06902 (E-mail: DYuh@stamhealth.org). J Thorac Cardiovasc Surg 2018;-:1-2 0022-5223/

Value analysis committees: Not just another committee to get out of

36.00 Copyright 2018 by The American Association for Thoracic Surgery https://doi.org/10.1016/j.jtcvs.2018.03.042

Heart and Heart-Lung Transplantation: An Update

From the Department of Surgery, Stamford Hospital, Stamford, Conn. Disclosures: Author has nothing to disclose with regard to commercial support. Received for publication Oct 31, 2017; accepted for publication Nov 10, 2017. Address for reprints: David D. Yuh, MD, FACS, FACC, One Hospital Plaza, PO Box 9317, Stamford, CT 06904 (E-mail: DYuh@stamhealth.org). J Thorac Cardiovasc Surg 2017;-:1-2 0022-5223/

Leflunomide prolongs pulmonary allograft and xenograft survival.

36.00 Copyright 2017 by The American Association for Thoracic Surgery https://doi.org/10.1016/j.jtcvs.2017.11.033

Prolongation of Cardiac Graft Survival with Anti-CD4Ig Plus hCTLA4Ig in Primates

Heart and heart-lung transplantation have been established as effective treatments for a wide variety of end-stage cardiopulmonary diseases. Recent years have seen refinements in surgical techniques for cardiopulmonary replacement as well as the selection and postoperative care of thoracic transplant recipients. Despite substantial clinical progress, however, significant problems remain, particularly donor organ shortage, graft rejection, opportunistic infection, and limited organ preservation techniques. Basic and clinical research are currently addressing these problems. In this brief review, we provide an update of our experiences with heart and heart-lung transplantation in the West (particularly at Stanford University), an outline of the active issues in the field, and some thoughts about the development of thoracic transplantation in Asia.