Hawley H. Seiler Resident Award. Transcriptional profile of brain injury in hypothermic circulatory arrest and cardiopulmonary bypass.
Hawley H. Seiler Resident Award. Transcriptional profile of brain injury in hypothermic circulatory arrest and cardiopulmonary bypass.
复制标题
DOI：
10.1016/j.athoracsur.2010.02.051
复制
发表时间：
2010-06
影响因子：
4.6
通讯作者：
Baumgartner, William A.
中科院分区：
文献类型：
--
作者：
Allen, Jeremiah G.;Weiss, Eric S.;Wilson, Mary Ann;Arnaoutakis, George J.;Blue, Mary E.;Talbot, C. Conover, Jr.;Jie, Chunfa;Lange, Mary S.;Troncoso, Juan C.;Johnston, Michael V.;Baumgartner, William A.
体外循环（CPB）低温停循环（HCA）后神经系统并发症的分子机制知之甚少。犬基因组测序允许分析单独HCA和CPB后的基因组变化。我们假设基因调控将随着损伤严重程度的增加而增加。犬在18°C下接受2小时HCA（n = 10）、1小时HCA（n = 8）或仅在32°C下接受2小时CPB（n = 8）。在每组中，在处理后8小时和24小时各处死一半。在神经学评分后，收获脑用于基因组分析。使用含有42，028个探针的犬寡核苷酸表达阵列分析海马RNA分离物。与之前的工作一致，接受2小时HCA的犬发生了严重的神经损伤。一小时的HCA造成中度临床损伤。单独心肺转流的临床评分正常。心脏搭桥、1小时HCA和2小时HCA组历史上表现出组织病理学损伤程度增加（先前发表）。探索性分析揭示了显著调节基因的差异（错误发现率<10%，绝对倍数变化≥ 1.2），差异基因表达随损伤严重程度增加而增加。在损伤后8小时和24小时，2小时HCA犬分别有502和1，057个基因受到调节; 1小时HCA犬有179和56个基因受到调节;单独CPB犬有5和0个基因受到调节。我们对HCA和CPB后犬脑的基因组图谱显示，与单独CPB的最小效应相比，1小时和2小时HCA诱导的基因调控显著增加。这增加了支持单独CPB的安全性和CPB对正常大脑的最小影响的神经学文献的主体，同时阐明了两者的基因组结果。
Little is known about the molecular mechanisms of neurologic complications after hypothermic circulatory arrest (HCA) with cardiopulmonary bypass (CPB). Canine genome sequencing allows profiling of genomic changes after HCA and CPB alone. We hypothesize that gene regulation will increase with increased severity of injury. Dogs underwent 2-hour HCA at 18°C (n = 10), 1-hour HCA (n = 8), or 2-hour CPB at 32°C alone (n = 8). In each group, half were sacrificed at 8 hours and half at 24 hours after treatment. After neurologic scoring, brains were harvested for genomic analysis. Hippocampal RNA isolates were analyzed using canine oligonucleotide expression arrays containing 42,028 probes. Consistent with prior work, dogs that underwent 2-hour HCA experienced severe neurologic injury. One hour of HCA caused intermediate clinical damage. Cardiopulmonary bypass alone yielded normal clinical scores. Cardiopulmonary bypass, 1-hour HCA, and 2-hour HCA groups historically demonstrated increasing degrees of histopathologic damage (previously published). Exploratory analysis revealed differences in significantly regulated genes (false discovery rate < 10%, absolute fold change ≥ 1.2), with increases in differential gene expression with injury severity. At 8 hours and 24 hours after insult, 2-hour HCA dogs had 502 and 1,057 genes regulated, respectively; 1-hour HCA dogs had 179 and 56 genes regulated; and CPB alone dogs had 5 and 0 genes regulated. Our genomic profile of canine brains after HCA and CPB revealed 1-hour and 2-hour HCA induced markedly increased gene regulation, in contrast to the minimal effect of CPB alone. This adds to the body of neurologic literature supporting the safety of CPB alone and the minimal effect of CPB on a normal brain, while illuminating genomic results of both.
登录
查看更多内容
影响因子：
4.6
作者：
Baumgartner, WA;Walinsky, PL;Johnston, MV
通讯作者：
Johnston, MV
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
158.5
作者：
Roach, GW;Kanchuger, M;Mangano, DT
通讯作者：
Mangano, DT
影响因子：
4.6
作者：
Barreiro, CJ;Williams, JA;Baumgartner, WA
通讯作者：
Baumgartner, WA