Techniques to harvest diseased human peripheral arteries and measure endothelial function in an ex vivo model.
Techniques to harvest diseased human peripheral arteries and measure endothelial function in an ex vivo model.
复制标题
在离体模型中采集患病人类外周动脉并测量内皮功能的技术。
DOI:
10.1016/j.jvs.2012.10.123
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发表时间:
2013
影响因子:
4.3
通讯作者:
Kashyap,VikramS
中科院分区:
文献类型:
--
作者:
Lakin,RyanO;Zhu,Weifei;Feiten,Lindsay;Kashyap,VikramS
ObjectiveEndothelial dysfunction has been studied in animal models. However, direct evidence of endothelial function from human vessels is limited. Our objectives were to optimize methods in harvesting human arteries from amputation specimens, determine endothelial function, and measure responsiveness tol-arginine, a nitric oxide precursor.MethodsFresh amputation specimens were transferred expeditiously from the operating room to the bench laboratory for dissection and arterial harvest in an Investigational Review Board-approved protocol. Popliteal and tibial vessels were examined in pilot experiments leading to the use of the anterior tibial artery in consecutive experiments. Human lower extremity anterior tibial artery segments were harvested from 14 amputation specimens. Specimens were rapidly collected and divided for endothelial-dependent relaxation (EDR) studies in a tissue bath apparatus, immunohistochemistry, and intravascular ultrasound-derived virtual histology. A total of 47 ring segments were studied. The data were compared with two-way analysis of variance.ResultsHuman lower extremity arteries exhibited low responsiveness to acetylcholine (EDR, 24.9%; acetylcholine, 10−4). L-arginine supplementation enhanced EDR by 38.5% (P< .0001).N-nitro-L-arginine methyl ester abrogated EDR (P< .0001) in vessels exposed to L-arginine. Arterial responsiveness was intact in all vessels (endothelial independent relaxation to sodium nitroprusside, 113.2% ± 28.1%). Histology and immunohistochemistry confirmed intact endothelium by morphometric analysis, cluster of differentiation 31, endothelial nitric oxide synthase, and arginase II staining. Intravascular ultrasound-derived virtual histology indicated atheroma burden was 11.9 ± 4.7 mm3/cm, and plaque stratification indicated fibrous morphology was predominant (59.9%; necrotic core, 16.9%; calcium, 11.2%). Variations in plaque morphology did not correlate with endothelial function or responsiveness to L-arginine.ConclusionsHuman lower extremity arteries demonstrate low baseline endothelial function in patients requiring amputation. Endothelial dysfunction is improved by L-arginine supplementation in an ex vivo model. These results support strategies to increase local levels of nitric oxide in human vessels.
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影响因子:
37.8
作者:
HODGSON, JM;MARSHALL, JJ
通讯作者:
MARSHALL, JJ
影响因子:
158.5
作者:
LUDMER, PL;SELWYN, AP;GANZ, P
通讯作者:
GANZ, P
影响因子:
24
作者:
M. Corretti;T. Anderson;E. Benjamin;D. Celermajer;F. Charbonneau;M. Creager;J. Deanfield;H. Drexler;M. Gerhard;D. Herrington;P. Vallance;J. Vita;R. Vogel
通讯作者:
R. Vogel
影响因子:
4.3
作者:
V. Kashyap;T. Reil;W. Moore;T. Hoang;H. Gelabert;R. Byrns;L. Ignarro;J. Freischlag
通讯作者:
J. Freischlag
DOI:
10.1073/pnas.84.24.9265
发表时间:
1987-12-01
影响因子:
11.1
作者:
IGNARRO, LJ;BUGA, GM;CHAUDHURI, G
通讯作者:
CHAUDHURI, G