Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model

Jason T. Fitzgerald, Matthew J. Sena, Kristen Nero Vandewalker, Jeremy R. Johnson, Stephen M Griffey, Alice F Tarantal, Peter A Barry, Michael B. McChesney, Rajendra Ramsamooj, Richard V Perez

Research output: Contribution to journalArticle

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Abstract

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 mm2 vs. 1.03 mm2, 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.

Original languageEnglish (US)
Pages (from-to)367-374
Number of pages8
JournalTransplantation
Volume78
Issue number3
DOIs
StatePublished - Aug 15 2004

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Primates
Allografts
Blood Vessels
Inflammation
Transplants
C-Reactive Protein
Tunica Intima
Transplantation
Thigh
Iliac Artery
Macaca mulatta
Blood Proteins
Pathologic Constriction
Tissue Donors
Kidney

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model. / Fitzgerald, Jason T.; Sena, Matthew J.; Vandewalker, Kristen Nero; Johnson, Jeremy R.; Griffey, Stephen M; Tarantal, Alice F; Barry, Peter A; McChesney, Michael B.; Ramsamooj, Rajendra; Perez, Richard V.

In: Transplantation, Vol. 78, No. 3, 15.08.2004, p. 367-374.

Research output: Contribution to journalArticle

Fitzgerald, Jason T. ; Sena, Matthew J. ; Vandewalker, Kristen Nero ; Johnson, Jeremy R. ; Griffey, Stephen M ; Tarantal, Alice F ; Barry, Peter A ; McChesney, Michael B. ; Ramsamooj, Rajendra ; Perez, Richard V. / Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model. In: Transplantation. 2004 ; Vol. 78, No. 3. pp. 367-374.
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abstract = "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 mm2 vs. 1.03 mm2, 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.",
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AU - Fitzgerald, Jason T.

AU - Sena, Matthew J.

AU - Vandewalker, Kristen Nero

AU - Johnson, Jeremy R.

AU - Griffey, Stephen M

AU - Tarantal, Alice F

AU - Barry, Peter A

AU - McChesney, Michael B.

AU - Ramsamooj, Rajendra

AU - Perez, Richard V

PY - 2004/8/15

Y1 - 2004/8/15

N2 - 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 mm2 vs. 1.03 mm2, 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.

AB - 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 mm2 vs. 1.03 mm2, 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.

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