Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model.
BACKGROUND
Occult systemic inflammation, as manifested by increased levels of C-reactive protein (CRP), identify patients at increased risk for renal allograft rejection. The mechanisms linking occult systemic inflammation to these adverse outcomes remain unclear. The purpose of this study was to examine the anatomic and physiologic effects of occult pretransplantation systemic inflammation on posttransplantation allograft outcome in a nonhuman primate model.


METHODS
Seventy-one healthy male Rhesus macaques were stratified into quartiles based on serum CRP. Five high quartile and six low quartile animals underwent common iliac artery transplantation from male donors. Duplex ultrasound measured graft flow at 3 weeks postoperatively; luminal narrowing was assessed by graft/femoral peak systolic velocity ratio. At 6 weeks, the grafts were harvested and morphometry studies were performed. Vessel wall changes were assessed by measuring the intimal medial area.


RESULTS
The allografts placed in high CRP quartile animals had more luminal narrowing by 3 weeks than those placed in low quartile animals, as evidenced by a higher mean graft/femoral peak systolic velocity ratio (1.6 vs. 0.90, P=0.006). Morphometry studies after graft harvest showed increased vessel wall area in the high quartile group versus the low quartile group (1.39 mm vs. 1.03 mm, P=0.018).


CONCLUSIONS
Occult pretransplantation systemic inflammation is associated with increased intimal thickening and stenosis after arterial allograft transplantation in a primate model. Additional studies are needed to confirm these results and to further investigate potential mechanisms linking pretransplantation systemic inflammation to adverse outcomes after transplantation.
Fitzgerald
Jason T
JT
Department of Surgery, University of California, Davis Medical Center, Sacramento, USA. hellfitz@aol.com
Sena
Matthew J
MJ
Vandewalker
Kristen Nero
KN
Johnson
Jeremy R
JR
Griffey
Stephen M
SM
Tarantal
Alice F
AF
Barry
Peter A
PA
McChesney
Michael B
MB
Ramsamooj
Rajendra
R
Perez
Richard V
RV
D000818:Animals; D001158:Arteries / Q000276:immunology / Q000503:physiopathology / Q000637:transplantation*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation; D008253:Macaca mulatta; D008297:Male; D023421:Models, Animal; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology / Q000502:physiology*
D015415:Biomarkers; D002097:C-Reactive Protein