Isolated coronary artery transplantation in pigs: a new model to study transplantation arteriosclerosis and humoral rejection.
BACKGROUND
Graft atherosclerosis is a major cause of death after heart transplantation; its causes are multifactorial and poorly understood. To determine whether specific sensitization to coronary artery antigens is a contributing factor, we developed an isolated coronary artery allotransplantation model in pigs.


METHODS
Of 46 Yucatan minipigs, 32 received a segment from a farm pig coronary artery into the common carotid artery (coronary allograft group) and 14 had a left to right common carotid artery autotransplant (carotid autograft group). No immunosuppressive drugs were given; all pigs received heparin for 5 days. We examined patency rates, histologic changes, and endothelial deposition of immunoglobulin G and M.


RESULTS
In the coronary allograft group, patency rates were 100% (11 of 11) at 1 to 29 days, 20% (2 of 10) at 30 to 89 days, and 0% (0 of 11) after 90 days (overall 40.6%, 13 of 32). Histologic findings included endothelial cell hyperplasia, intimal proliferation, medial necrosis, adventitial inflammation, and ultimately luminal thrombosis. Deposition of immunoglobulin G and M was examined in the patent grafts and was seen in 90.9% (10 of 11) of grafts from days 1 to 29 and in the two patent but partially occluded grafts at 41 and 56 days. All carotid autografts except one (92.8%, 13 of 14) were patent up to 140 days and showed no or mild focal intimal thickening with normal media and adventitia. Deposition of immunoglobulin could not be detected in the autograft group.


CONCLUSIONS
In this pig model of coronary artery allotransplantation, typical histologic findings of graft atherosclerosis are produced. Deposition of immunoglobulin G and M occurs early and is associated with endothelial cell hyperplasia and intimal proliferation. This model may be useful for the study of graft atherosclerosis and assessment of interventions designed to halt its progression.
Tixier
D B
DB
Division of Cardiothoracic Surgery, Cardiology, and Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
Czer
L S
LS
Fishbein
M C
MC
Blanche
C
C
Admon
D
D
Amador
R
R
Albert
G D
GD
Trento
A
A
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology* / Q000473:pathology; D017536:Carotid Artery, Common / Q000601:surgery* / Q000637:transplantation; D003331:Coronary Vessels / Q000637:transplantation*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006965:Hyperplasia / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M