Microsurgical Models in Rats for Transplantation Research

Preclinical experimental transplantation research that is based on microsurgical models in rats fulfills two indispensable conditions for modern organ transplanta­ tion research: Almost all organ grafts can be performed on the rat with an amount of technical effort that is still justifiable. Thus transplantation models that are analogous to human organ transplantation can be developed, tested, and evaluated. This fulfills a necessary condition from the standpoint of surgery. With the species rat, we have a great variety of genetically different inbred strains. From the immunological point of view this is an indispensable prerequisite for the investigation of preclinical transplantation models that can be expected to produce controllable, reproducible results. In vivo experimental results can be supplemented by and correlated to in vitro tests. Lately these experimental results are being greatly expanded and more precisely defined by the application of immunohistological methods that have been established recently in Kiel. In this book we hope to present a cross section of the microsurgical models in use today and of current immunological and immunohistological models. Furthermore, we wish to record the present state of microsurgical organ transplantation research and to show its relationship to the current state and development of clinical organ transplantation. A special aspect of our Kiel research group is the long-term, well-functioning, interdisciplinary cooperation between surgery, immunology, and pathology. Through this cooperation we attempt to provide an atmosphere in which theoretical and practical viewpoints can mutually influence each other.

A. Microsurgical Models and Techniques.- History and Development of Experimental Microsurgery in Rats.- Reflections on the Requirements and Perspectives of a Microsurgical Research Group.- Techniques of Microsurgical Vascular Anastomoses in Experimental Microsurgery.- Heart Transplantation in Rats.- Accessory Heart Transplantation in the Neck: A Simple Model in the Rat Using the Cuff Technique for Vascular Anastomoses.- Microvascular Pulmonary Transplantation in Rats.- Spleen and Vascularized Skin Flap Transplantation.- Renal Transplantation in the Rat.- Microsurgical Technique for Small-Intestine Transplantation.- Various Techniques of Experimental Pancreas Transplantation in the Rat.- Experiences in Rat Pancreatic Islet-Cell Isolation and Transplantation.- Technique for Orthotopic Rat Liver Transplantation.- B. Immunological Principles.- Theoretical Aspects of Rat Organ Transplantation.- Immunogenetic Aspects of Organ Transplantation in the Rat.- C. Results of Vessel and Heart Transplantation.- Venovenous Allotransplantation in the Rat.- The Rejection Response to Segmental Grafts of the Femoral Artery in Inbred Rat Strains.- Factors Influencing Endothelial-Cell Viability During Procurement and Preservation of Valve Allografts.- The Rat Model as Precursor of Clinical Lymph Vessel Transplantation.- Microstructure of Allogeneic Lymph Vessel Transplants in the Rat.- Immunogenetic Basis of Heart Transplantation.- Cyclosporin A in Heart Allografts in Rats.- D. Results of Small-Instestine Transplantation, Graft Versus Host Reaction, and Host Versus Graft Reaction.- Monitoring of Rejection and Absorption Studies After Small-Bowel Transplantation in the Dog Model.- Migration of Donor Passenger Cells During Rat Cardiac and Intestinal Allograft Rejection.- Rejection and Graft Versus Host Reaction Following Small-Bowel Transplantation and Methods of Circumventing Them.- Immunological Reactions Induced by Graft Versus Host Reaction Following Small-Bowel Transplantation.- E. Pancreas Transplantation Versus Islet Transplantation.- Combined Pancreas and Kidney Transplantation in the Rat.- Immunological Characteristics of Vascularized Pancreas Transplantation.- Is Preserved Exocrine Secretion Mandatory for Optical Endocrine Function in Vascularized Pancreas Transplantation?.- The Effect of Temporary Cyclosporin A Treatment on the Endocrine Function of Pancreaticoduodenal Allografts in the Rat.- The Influence of Exocrine Secretion Management on Graft Survival in Different Pancreatic Transplant Models.- Investigations of Glucose Tolerance Following Pancreatic Transplantation in Rats with Streptozotocin-Induced Diabetes.- Successful Allotransplantation of Islets as Composite Graft in a Strong Rejection Model.- The Immunogenicity of Pancreatic Islets.- A New Approach to Experimental Pancreatic Islet Transplantation: Ultraviolet Irradiation.- Characterization of Pancreas Islet-Cell Ractivity with Various Immune Sera.- F. Results of Liver Transplantation.- Heterotopic Auxiliary Liver Transplantation with Respect to Its Clinical Application.- Accelerated But Not Hyperacute Rejection of Liver Allografts in Hypersensitized Rats.- Orthotopic Versus Auxiliary Liver Transplantation.- Fine-Needle Aspiration Cytology of Orthotopic Liver Allografts in Rats.- Immunosuppressive Effects of Liver Grafts in the Rat.- Graft Tolerance After Orthotopic Liver Transplantation in a Primarily Nontolerant Strain Combination Following Temporary Cyclosporin A Treatment.- Liver Transplantation and Cyclosporin A Therapy: Induction of Tolerance in a Strong Rejection Combination.- Study of the Cellular Immunity of Tolerance Induced by Liver Grafting in the Rat.- Mechanisms of Tolerance in Rat Liver Transplantation.- G. Miscellaneous: Microsurgical Organ Transplantation.- Decreased Graft Versus Host Reaction After Portal Venous Drainage of Spleen Grafts in Inbred Strains of Rats.- Do Transplants with Venous Drainage into the Portal System Undergo Delayed Rejection?.- Transplantation of Chimeric Organs: Implications for the Passenger-Cell Concept.- Orthotopic Rat Renal Transplantation Using the Cuff Method.- Effect of Cyclosporin on the Function of the Proximal Tubule and Loop of Henle in the Rat Kidney.- Cyclosporion A Blood Levels in Rats After Different Modes of Administration.- Orthotopic Transplantation of the Fallopian Tube, Ovary, and Segment of the Uterus in Inbred Rats.- Allogeneic and Xenogeneic Biografts in Reconstructive Surgery of the Trachea.- H. Relevance of Experimental Organ Transplantation in the Rat to Clinical Organ Transplantation.- Immunological Mechanisms in Clinical Organ Transplantation.- Immunohistological Analysis of Late Cellular Rejection and Cyclosporin-A-Resistant Acute Rejection in Human Kidney Allograft: Evidence of Delayed-Type Hypersensitivity Reaction Mechanisms.- Immunological Monitoring of Heart Transplant Patients: Clinical and Experimental Studies.- Intestinal Transplantation: Laboratory Experience and Clinical Consequences.- Experience with Segmental Pancreatic Transplantation in Stockholm.- Clinical Experience in Islet Transplantation.- Present Status of Clinical Liver Transplantation and Potential Developments Based on Experimental Microsurgical Models.- Present Status of Clinical Kidney Transplantation and Possible Developments with Respect to Experimental Microsurgery Models.- Conclusion.