TY - JOUR
T1 - A model of xenograft hyperacute rejection attenuates endothelial nitric oxide production
T2 - A mechanism for graft vasospasm?
AU - Cable, David G.
AU - Hisamochi, Kunikazu
AU - Schaff, Hartzell V.
N1 - Funding Information:
Supported in part by The Mayo Foundation. Performed during DGC tenure as a Clinical Investigator Research Fellow.
PY - 1999/3
Y1 - 1999/3
N2 - Background: The deposition of complement components within grafts, complement consumption, and prolongation of graft function by complement inactivation imply a pivotal role for complement in xenograft hyperacute rejection. The current investigations examined the endothelial production of vasoactive substances in pulmonary arteries during simulated hyperacute rejection. Methods and Results: Canine pulmonary arteries were suspended in organ chambers and exposed to either autologous canine serum for 90 minutes or heterologous porcine serum for 30, 60, or 90 minutes. Following serum exposure, the vessels were allowed a one-hour equilibration in buffered crystalloid solution. Dose-response curves were obtained with acetylcholine, sodium nitroprusside, and calcium ionophore A23187 following contraction with phenylephrine (10-6M) in the presence of indomethacin (10-5M). Receptor- dependent, endothelial-dependent relaxations to acetylcholine (10-9-10- 4M) were impaired with 30-, 60-, or 90-minute porcine serum exposure when compared to vessels exposed to autologous canine serum (n = 10, 7, 9, respectively; p < .05; 2-way ANOVA). Receptor-independent, endothelial- dependent relaxations to calcium inophore (10-9-10-6M) were significantly impaired at 60- and 90-minute porcine exposures only (n = 7, 8; p < .05). Endothelial-independent relaxations to sodium nitroprusside (10-9-10-4M) were not impaired with either canine or porcine serum exposure. Oxyhemoglobin (10-6M) abolished acetylcholine-mediated relaxations, indicating that nitric oxide was the predominant mediator. Conclusions: Simulated hyperacute xenograft rejection impairs endothelium-dependent relaxation of canine pulmonary arteries. Both basal and stimulated production of nitric oxide is impaired by heterologous serum exposure and, subsequently, complement activation. Reduced production of nitric oxide may explain, in part, the vasospasm and thrombosis of xenografts during hyperacute rejection.
AB - Background: The deposition of complement components within grafts, complement consumption, and prolongation of graft function by complement inactivation imply a pivotal role for complement in xenograft hyperacute rejection. The current investigations examined the endothelial production of vasoactive substances in pulmonary arteries during simulated hyperacute rejection. Methods and Results: Canine pulmonary arteries were suspended in organ chambers and exposed to either autologous canine serum for 90 minutes or heterologous porcine serum for 30, 60, or 90 minutes. Following serum exposure, the vessels were allowed a one-hour equilibration in buffered crystalloid solution. Dose-response curves were obtained with acetylcholine, sodium nitroprusside, and calcium ionophore A23187 following contraction with phenylephrine (10-6M) in the presence of indomethacin (10-5M). Receptor- dependent, endothelial-dependent relaxations to acetylcholine (10-9-10- 4M) were impaired with 30-, 60-, or 90-minute porcine serum exposure when compared to vessels exposed to autologous canine serum (n = 10, 7, 9, respectively; p < .05; 2-way ANOVA). Receptor-independent, endothelial- dependent relaxations to calcium inophore (10-9-10-6M) were significantly impaired at 60- and 90-minute porcine exposures only (n = 7, 8; p < .05). Endothelial-independent relaxations to sodium nitroprusside (10-9-10-4M) were not impaired with either canine or porcine serum exposure. Oxyhemoglobin (10-6M) abolished acetylcholine-mediated relaxations, indicating that nitric oxide was the predominant mediator. Conclusions: Simulated hyperacute xenograft rejection impairs endothelium-dependent relaxation of canine pulmonary arteries. Both basal and stimulated production of nitric oxide is impaired by heterologous serum exposure and, subsequently, complement activation. Reduced production of nitric oxide may explain, in part, the vasospasm and thrombosis of xenografts during hyperacute rejection.
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U2 - 10.1016/S1053-2498(98)00023-0
DO - 10.1016/S1053-2498(98)00023-0
M3 - Article
C2 - 10328141
AN - SCOPUS:0032918079
SN - 1053-2498
VL - 18
SP - 177
EP - 184
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 3
ER -