这项研究是由授予美国公民在癫痫（治愈）研究的SLB支持。

<p class="jove_title"&gt; 1。材料构造</p&gt;<ol&gt;<li颈内静脉导管斜面的一端，从PE - 50聚乙烯管件（100毫米）建造，然后用充满肝素盐水（肝素50 U / mL生理盐水）。</li&gt;<li&gt;心电图记录电极的构造从两个绝缘的银线（30AWG）的100毫米的长度。被剥离的两条电线的一端焊接到一个microconnector，是扭曲形成了第三条线是地面和绝缘。五毫米的绝缘层剥去电线的末端，并丢弃。</li&gt;</ol&gt;<p class="jove_title"&gt; 2。植入颈静脉导管</p&gt;<ol&gt;<li&gt;麻醉聚氨酯动物管理，IP（1.2克/公斤）。</li&gt;<li&gt;常规检查（间隔10分钟）评估踏板戒断反应和/或眼睛反射麻醉深度。如果需要，补充麻醉。</li&gt;<li&gt;后的动物，在适当的麻醉平面，剃除的颈部右侧，从锁骨到下巴。</li&gt;<li&gt;在皮肤上面的颈内动脉一纵形切口（10-15毫米），并打开切口。</li&gt;<li&gt;使用钝性分离技术，传播底层的肌肉，找到并分离右颈静脉。</li&gt;<li&gt;下两件手术丝绸（＃2），颈内静脉和位置的喙和尾鳍切口部分缝合。铁喙结扎停止通过静脉流。</li&gt;<li收回尾结扎升空的基本组织的船只，使一小截。然后插入充满肝素（50 U / ml生理盐水）PE - 50聚乙烯导管（长度为100毫米）的斜面结束，并提前提示右心房水平约8毫米。</li&gt;<li为了安全的导管，配合尾椎周围船只和导管结扎。最后，关闭或者创口夹子或缝合伤口。</li&gt;<li&gt;在植入的导管外露端是用止血钳或夹紧插入附件输液泵之前，防止血流。</li&gt;</ol&gt;<p class="jove_title"&gt; 3。植入管治电极</p&gt;<ol&gt;<li&gt;放置在它的后面的动物和刮胡子的胸部。</li&gt;<li&gt;电极的位置，使两纵切口（≈10毫米），一个在右上和左下象限胸部，和免费上覆皮肤暴露胸肌肉。</li&gt;<li&gt;缝合暴露5毫米的银电极丝的秘诀之一，在暴露部位的胸肌肉，皮下放置在地面电极。</li&gt;<li&gt;关闭伤口剪辑的切口，并插入到录音设备microconnector。</li&gt;<li松散包装的动物在手术过程中保持体温的毛巾。</li&gt;</ol&gt;<p class="jove_title"&gt; 4。记录心电图</p&gt;<ol&gt;<li&gt;录音使用一个PowerLab系统数据采集系统和Macintosh计算机或类似的硬件/软件（放大，50X;过滤，1-1000赫兹）。</li&gt;<li&gt; 20分钟20-30分钟的平衡时间，记录心电图。</li&gt;</ol&gt;<p class="jove_title"&gt; 5。诱发室性心律失常</p&gt;<ol&gt;<li&gt;颈内静脉导管连接到一个远程的注射器放置在一个可编程的输液泵。</li&gt;<li&gt;启动乌头输液的速度，以提供一个恒定剂量为5微克/公斤/分钟7分钟。</li&gt;<li&gt;下面的心室颤动或输液期间结束，安乐死的动物，使用经批准的过程。</li&gt;</ol&gt;<p class="jove_title"&gt; 6。心电图分析</p&gt;<ol&gt;<li&gt; QT间期代表心室电活动的总工期。图1显示了一个模型的心电图记录及QT间隔时间。计算开始Q波和T波超过五分钟的时间间隔在20分钟的录音期间获得的所有记录心跳终止之间的平均时间。</li&gt;<li要正确QT间期的心率（QT间期）的差异，使用Bazett的公式，QT间期= QT /（RR）<sup&gt;半</sup&gt;，其中RR是心跳之间的间隔时间平均。 RR间隔是连续在分析期间获得的Q -波之间的时间计算。</li&gt;<li&gt; QT离散度（QTd）的计算方法是记录每个动物的最大QT间期减去最小QT间。</li&gt;</ol&gt;<p class="jove_title"&gt; 7。心率变异性分析</p&gt;<ol<li用于自动计算心率变异的时间和/或光谱&gt;软件程序（即LabChart 7，ADInstruments公司），分析在分析期间获得的RR间隔的变化。</li</ol&gt;<p class="jove_title"&gt; 8。室性心律失常的敏感性分析</p&gt;<ol<li&gt;从开始乌头输液计算延迟室性早搏收缩（PVC，图2，第1小组），室性心动过速（VT，图2，第2小组）和心室颤动（VF，图2，第3小组）。</li</ol&gt;<p class="jove_title"&gt; 9。代表性的成果</p&gt;<p class="jove_content"&gt;图。 3说明了在谱域（均方根RR间隔的标准偏差的平方，RMSSD）在对照组大鼠在动物中，经历了SE的前一个星期测试的心率变异性的一项措施。这种心率变异性的措施，这代表在心脏功能的副交感神经控制的变化<sup&gt; 26</sup&gt;，显着降低癫痫持续状态的动物。图4，同时校正QT间隔（QT间期，A组）和QT离散​​度（QTd，B组）显着增加了两个星期，以下SE<sup&gt; 27</sup&gt;。两者合计，这些数据预测，SE增加室性心律失常的风险。这一预测的结果证实，乌头输液期间要促使在这些研究中观察到的实验性心律失常（PVC，VT，VF）在动物明显较小东南（图5）<sup&gt; 27</sup&gt;。</p&gt;<p class="jove_content"<img src="/files/ftp_upload/2726/2726fig1.jpg" alt="figure 1" /<br /<strong&gt;图1。</strong&gt;型号心电图记录显示P，QRS波和T波的正常心跳。 QT间期的计算公式为虚线之间的时间。</p&gt;<p class="jove_content"<img src="/files/ftp_upload/2726/2726fig2.jpg" alt="figure 2" /<br /<strong&gt;图2。第1小组）</strong被隔离&gt;室性早搏（室早）心室的收缩（二）正常心跳之间出现（一个）。聚氯乙烯录音的特点是P和T波的情况下。<strong&gt;第2小组</strong&gt;心室性心动过速（VT）是一个系列多个室性早搏（三）没有正常心跳（一）发生。<strong&gt;第3小组</strong&gt;心室颤动（VF），是有迹可寻的节奏和协会之间没有QRS波和P波（四）缺乏。</p&gt;<p class="jove_content"<img src="/files/ftp_upload/2726/2726fig3.jpg" alt="figure 3" /<br /<strong&gt;图3。</strong&gt;根平均平方的标准差（RMSSD;毫秒）在对照组大鼠在动物测试前发生癫痫持续状态（SE）1周观察心跳之间的间隔。 ** P &lt;0.01与对照组比较。</p&gt;<p class="jove_content"<img src="/files/ftp_upload/2726/2726fig4.jpg" alt="figure 4" /<br /<strong&gt;图4。</strong&gt;平均校正QT间隔（A组）和QT离散​​度（B组），从控制动物（续）从大鼠发生癫痫持续状态（SE）两个星期前测试得到的心电图记录计算。 * P &lt;0.05相比，连拍。 （梅特卡夫，等人，上午生理学，心脏和保监会2009年，上午，许可使用从生理学SOC<sup&gt; 27</sup&gt;）。</p&gt;<p class="jove_content"<img src="/files/ftp_upload/2726/2726fig5.jpg" alt="figure 5" /<br /<strong&gt;图5。</strong延迟（秒）之间的乌头输液的启动和第一室性早搏收缩（PVC），心室性心动过速（VT）和心室颤动（VF）（续）在控制动物和大鼠发生癫痫持续状态（SE）两个星期前的测试。 * P &lt;0.05，** P &lt;0.01相比，到Cont。 （梅特卡夫，等人，上午生理学，心脏和保监会2009年，上午，许可使用从生理学SOC<sup&gt; 27</sup&gt;）。</p&gt;

<ol>
	<li>Chugh, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determinants+of+prolonged+QT+interval+and+their+contribution+to+sudden+death+risk+in+coronary+artery+disease:+The+Oregon+sudden+unexpected+death+study.">Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease: The Oregon sudden unexpected death study.</a> Circulation. 119, 663-670 (2009).</li><li>Darbar, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensitivity+and+specificity+of+QTc+dispersion+for+identification+of+risk+of+cardiac+death+in+patients+with+peripheral+vascular+disease.">Sensitivity and specificity of QTc dispersion for identification of risk of cardiac death in patients with peripheral vascular disease.</a> BMJ. 312, 874-878 (1996).</li><li>Bruyne, M. C. d. e. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=QTc+dispersion+predicts+cardiac+mortality+in+the+elderly:+The+Rotterdam+study.">QTc dispersion predicts cardiac mortality in the elderly: The Rotterdam study.</a> Circulation. 97, 467-472 (1998).</li><li>Malik, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heart+rate+variability:+standards+of+measurement,+physiological+interpretation,+and+clinical+use.">Heart rate variability: standards of measurement, physiological interpretation, and clinical use.</a> Circulation. 93, 1043-1065 (1996).</li><li>Grippo, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+susceptibility+to+ventricular+arrhythmias+in+a+rodent+model+of+experimental+depression.">Increased susceptibility to ventricular arrhythmias in a rodent model of experimental depression.</a> Am. J. Physiol. 286, H619-H626 (2004).</li><li>Li, M., Wang, J., Xie, H. H., Shen, F. M., Su, D. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+susceptibility+of+ventricular+arrhythmia+to+aconitine+in+conscious+hypertensive+rats.">The susceptibility of ventricular arrhythmia to aconitine in conscious hypertensive rats.</a> Acta. 28, 211-215 (2007).</li><li>Beig, M. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Voluntary+exercise+does+not+affect+stress-induced+tachycardia,+but+improves+resistance+to+cardiac+arrhythmias+in+rats.">Voluntary exercise does not affect stress-induced tachycardia, but improves resistance to cardiac arrhythmias in rats.</a> Clin. Exp. Pharm. Physiol. , (2010).</li><li>Hazari, M. S., Haykai-Coates, N., Winsett, D. W., Costa, D. L., Farraj, A. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+single+exposure+to+particulate+or+gaseous+ari+pollution+increases+the+risk+of+aconitine-induced+cardiac+arrhythmia+in+hypertensive+rats.">A single exposure to particulate or gaseous ari pollution increases the risk of aconitine-induced cardiac arrhythmia in hypertensive rats.</a> Toxicol. Sci. 112, 532-542 (2009).</li><li>Amran, M. S., Hashimoto, K., Homma, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+sodium-calcium+exchange+inhibitors,+KB-R7943+and+SEA0400,+on+aconitine-induced+arrhythmias+in+guinea+pigs+in+vivo,+in+vitro,+and+in+computer+simulation+studies.">Effects of sodium-calcium exchange inhibitors, KB-R7943 and SEA0400, on aconitine-induced arrhythmias in guinea pigs in vivo, in vitro, and in computer simulation studies.</a> J. Pharmacol. Exp. Ther. 310, 83-89 (2004).</li><li>Klekot, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiarrhythmic+activity+of+a+membrane-protecting+agent+Sal'magin+in+rats+with+aconitine-induced+arrhythmias.">Antiarrhythmic activity of a membrane-protecting agent Sal'magin in rats with aconitine-induced arrhythmias.</a> Bull. Exp. Biol. Med. 142, 209-211 (2006).</li><li>Lowenstein, D. H., Alldredge, B. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Status+Epilepticus.">Status Epilepticus.</a> New England J. Med. 338, 970-976 (1998).</li><li>Walker, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Status+epilepticus:+an+evidence+based+guide.">Status epilepticus: an evidence based guide.</a> BMJ. 331, 673-677 (2005).</li><li>Shorvon, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Status epilepticus: its clinical features and treatment in children and adults. , (1994).</li><li>Boggs, J. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+monitoring+prior+to+and+at+the+time+of+death+in+status+epilepticus.">Hemodynamic monitoring prior to and at the time of death in status epilepticus.</a> Epilepsy Res. 31, 199-209 (1998).</li><li>Walton, N. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systemic+effects+of+generalized+convulsive+status+epilepticus.">Systemic effects of generalized convulsive status epilepticus.</a> Epilepsia. 34, S54-S58 (1993).</li><li>Boggs, J. G., Painter, J. A., DeLorenzo, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analysis+of+electrocardiographic+changes+in+status+epilepticus.">Analysis of electrocardiographic changes in status epilepticus.</a> Epilepsy Res. 14, 87-94 (1993).</li><li>Painter, J. A., Shiel, F. O., DeLorenzo, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+pathology+findings+in+status+epilepticus.">Cardiac pathology findings in status epilepticus.</a> Epilepsia. 34, 30-30 (1993).</li><li>Lathers, C. M., Schraeder, P. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+pharmacology:+drugs+as+a+benefit+and/or+risk+in+sudden+unexpected+death+in+epilepsy.">Clinical pharmacology: drugs as a benefit and/or risk in sudden unexpected death in epilepsy.</a> J. Clin. Pharmacol. 42, 123-126 (2002).</li><li>Dashieff, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sudden+unexpected+death+in+epilepsy:+a+series+from+an+epilepsy+surgery+program+and+specualtion+of+the+relationship+to+sudden+cardiac+death.">Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and specualtion of the relationship to sudden cardiac death.</a> J. Clin. Neurophysiol. 8, 216-222 (1991).</li><li>Tigaran, P. -. C. o. d. r. e. a., Dalager-Pedersen, S., Baandrup, S., Dam, U., M, ., Vesterby-Charles, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sudden+unexpected+death+in+epilepsy:+is+death+by+seizures+a+cardiac+event.">Sudden unexpected death in epilepsy: is death by seizures a cardiac event.</a> Am. J. Forensic Med. Pathol. 26, 99-105 (2005).</li><li>Leung, H., Kwan, P., Elger, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Finding+the+missing+link+between+ictal+bradyarrhythmia,+ictal+asystole,+and+sudden+unexpected+death+in+epilepsy.">Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy.</a> Epilepsy and Behavior. 9, 19-30 (2006).</li><li>Nei, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EEG+and+ECG+in+sudden+unexplained+death+in+epilepsy.">EEG and ECG in sudden unexplained death in epilepsy.</a> Epilepsia. 45, 338-345 (2004).</li><li>Dudek, F. E., Clark, S., Williams, P. A., Grabenstatter, H. L., Pitkanen, A., Schwartzkroin, P. A., Moshe, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Models of Seizures and Epilepsy. , 415-432 (2006).</li><li>Turski, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Limbic+seizures+produced+by+pilocarpine+in+rats:+behavioral+electroencephalographic,+and+neuropathological+study.">Limbic seizures produced by pilocarpine in rats: behavioral electroencephalographic, and neuropathological study.</a> Behav. Brain Res. 9, 315-335 (1989).</li><li>Kulkarni, S. K., George, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lithium-pilocarpine+neurotoxicity:+a+potential+model+of+status+epilepticus.">Lithium-pilocarpine neurotoxicity: a potential model of status epilepticus.</a> Methods Find. Exp. Clin. Pharamacol. 17, 551-567 (1995).</li><li>Stein, P. K., Bosner, M. S., Kleiger, R. E., Conger, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hart+rate+variability:+a+measure+of+cardiac+autonomic+tone.">Hart rate variability: a measure of cardiac autonomic tone.</a> Am. Heart J. 127, 1376-1381 (1994).</li><li>Metcalf, C. S., Poelzing, S., Little, J. G., Bealer, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Status+epilepticus+induces+cardiac+myofilament+damage+and+increased+susceptibility+to+arrhythmias+in+rat.">Status epilepticus induces cardiac myofilament damage and increased susceptibility to arrhythmias in rat.</a> Am. J. Physiol. 297, H2120-H2127 (2009).</li></ol>

所描述的过程的两个方面是至关重要的。首先，乌头管理率心必须相当于整个动物。这需要安置的颈内静脉导管提示心一致，并仔细调整输液速度。必须平等地以适当的评价室性心律失常的相对改变易感性的发病率乌头交付心中。如果乌头交付变化，则心律失常的延迟可能是由于药物浓度的差异，而不是在心脏功能的改变。其次，编制和心电图记录电极放置必须清楚可辨别的P，QRS波，T波与产量无瑕疵的录音。虽然心率，心率变异性，室性心律失常的发生可从仅QRS波，QT间期和QTd的确定必须计算从含有明确的Q波的发病和T波终止录音。 这些技术的一个明显的限制是，他们是在麻醉动物进行的。然而，这是必要的，原因有两个。 1）由于心电图电极植入骨骼肌肉组织，他们是在清醒大鼠的运动过程中产生的工件。这些非心脏信号往往掩盖了心电图心功能进行适当的分析所必需的活动。 2）乌头碱诱发心律失常的诱发提高一个潜在的伦理问题时，有意识的动物。 这些程序允许几家接受SCD的预后指标的量化，直接分析，在相同的动物的室性心律失常的易感性。这些技术是有价值的确定相对的心脏风险，以及心脏疗法的疗效，在癫痫，任何病理具有致命性室性心律失常，可在啮齿类动物为蓝本的关联。

methods for ecg evaluation of indicators of cardiac risk, and susceptibility to aconitine-induced arrhythmias in rats following status epilepticus

在一些病理条件下，致命的心律失常死亡率。建立一个非侵入性，容易获得的心电图（ECG）获得多项参数，验证患心肌病的患者的预后指标的心脏风险。心率增快，心率变异性（HRV）下降，增加的持续时间和心室电活动的变化（QT间期），都表明增强心脏的风险1-4。在动物模型中，它是有价值的，比较这些心电图派生变量和药敏实验诱发心律失常。静脉输液心律失常剂乌头已被广泛用于评估在一系列的实验条件下，包括5抑郁症和高血压6动物模型的心律失常易感性， 以下 7锻炼和接触到的空气污染物 8，以及确定的抗心律失常9,10药理剂的疗效 。 应该指出，在人类QT离散度，是衡量整个全套的信息从一个标准的12导联心电图QT间隔变化。因此，在本议定书中所描述的大鼠从2导联心电图QT分散的措施，是从人类的心电图记录计算，不同。这代表在翻译从人类临床用药的啮齿类动物中获得的数据的限制。 癫痫持续状态（SE）是一个单一的扣押或一系列不断反复发作，持久的死亡率超过30 分钟11,12 11,12，结果20％的案件 13 。许多人的生存本身，而是死于内30 天 14,15 。这个延迟死亡率（S）的机制尚不完全清楚。有人曾建议，致命的室性心律失常的贡献很多，这些死亡的 14-17 。除了 ​​向东南，经历自发性反复发作，如癫痫，的患者在癫痫（SUDEP）18有关的过早突然和意外死亡的风险。与SE，SUDEP调解的确切机制尚不清楚。有人曾提出，心室的异常，并导致心律失常作出了重大贡献 18-22 。 调查扣押相关的心源性死亡，和心脏疗法的疗效机制，有必要获得心源性风险指标和评估癫痫动物模型23-25 ​​心律失常的易感性。在这里，我们描述了心电图电极植入实验室只Sprague - Dawley鼠（褐家鼠）的方法，SE，收集和分析的心电图记录，四乌头输液期间和诱导的心律失常。 这些程序可以用来直接确定之间的关系心电图衍生的措施，以室性心律失常的心电活动和易感性，癫痫的大鼠模型，或与心源性猝死的风险增加相关的任何病理。

Watch this Scientific Journal Video about Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus at JoVE.com

Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

测量心电图（ECG）的心电活动，和心脏危险因素和心律失常的易感性在大鼠癫痫持续状态（SE）的分析技术进行了阐述。

心电图心脏风险评价指标和乌头碱诱发大鼠心律失常的易感性继癫痫持续状态的方法

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily ...

methods-for-ecg-evaluation-indicators-cardiac-risk-susceptibility-to

Nanyang Technological University

Research

JoVE Journal

Medicine

17.7K 次观看.  University of Utah. 测量心电图（ECG）的心电活动，和心脏危险因素和心律失常的易感性在大鼠癫痫持续状态（SE）的分析技术进行了阐述。

视频: Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease

Lipoxygenase (LOX) activity has been implicated in neurodegenerative disorders such as Alzheimer&#39;s disease, but its effects in Parkinson&#39;s disease (PD) pathogenesis are less understood. Gene-environment interaction models have utility in unmasking the impact of specific cellular pathways in toxicity that may not be observed using a solely genetic or toxicant disease model alone.&#160;To evaluate if distinct LOX isozymes selectively contribute to PD-related neurodegeneration, transgenic (i.e. 5-LOX and 12/15-LOX deficient) mice can be challenged with a toxin that mimics cell injury and death in the disorder.&#160;Here we describe the use of a neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces a nigrostriatal lesion to elucidate the distinct contributions of LOX isozymes to neurodegeneration related to PD. The use of MPTP in mouse, and nonhuman primate, is well-established to recapitulate the nigrostriatal damage in PD.&#160;The extent of MPTP-induced lesioning is measured by HPLC analysis of dopamine and its metabolites and semi-quantitative Western blot analysis of striatum for tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine. To assess inflammatory markers, which may demonstrate LOX isozyme-selective sensitivity, glial fibrillary acidic protein (GFAP) and Iba-1 immunohistochemistry are performed on brain sections containing substantia nigra, and GFAP Western blot analysis is performed on striatal homogenates.&#160;This experimental approach can provide novel insights into gene-environment interactions underlying nigrostriatal degeneration and PD.

Lipoxygenase (LOX) isozymes can generate products that may increase or decrease neuroinflammation and neurodegeneration.&#160;A gene-environment interaction study could identify LOX isozyme-specific effects. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of nigrostriatal damage in two LOX isozyme-deficient transgenic lines allows for comparison of the contribution of LOX isozymes on dopaminergic integrity and inflammation.

基因-环境相互作用模型揭开帕金森病的隐形易感机制

Lipoxygenase (LOX) activity has been implicated in neurodegenerative disorders such as Alzheimer&#39;s disease, but its effects in Parkinson&#39;s disease ...

科研

医学

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50&#8211;60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.

We describe a stepwise procedure for creating pressure overload and left ventricular hypertrophy in Wistar rats by constriction of the ascending aorta using a small metallic clip. This model is extensively used for studying remodeling changes during cardiac hypertrophy and for identifying and evaluating strategies for regression of such changes.

大鼠建立压力超负荷心肌肥厚模型在升主动脉缩窄

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart ...

Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats

The kidney normally functions to maintain hemodynamic homeostasis and is a major site of damage caused by drug toxicity. Drug-induced nephrotoxicity is estimated to contribute to 19- 25% of all clinical cases of acute kidney injury (AKI) in critically ill patients. AKI detection has historically relied on metrics such as serum creatinine (sCr) or blood urea nitrogen (BUN) which are demonstrably inadequate in full assessment of nephrotoxicity in the early phase of renal dysfunction. Currently, there is no robust diagnostic method to accurately detect hemodynamic alteration in the early phase of AKI while such alterations might actually precede the rise in serum biomarker levels. Such early detection can help clinicians make an accurate diagnosis and help in in decision making for therapeutic strategy. Rats were treated with Cisplatin to induce AKI. Nephrotoxicity was assessed for six days using high-frequency sonography, sCr measurement and upon histopathology of kidney. Hemodynamic evaluation using 2D and Color-Doppler images were used to serially study nephrotoxicity in rats, using the sonography. Our data showed successful drug-induced kidney injury in adult rats by histological examination. Color-Doppler based sonographic assessment of AKI indicated that resistive-index (RI) and pulsatile-index (PI) were increased in the treatment group; and peak-systolic velocity (mm/s), end-diastolic velocity (mm/s) and velocity-time integral (VTI, mm) were decreased in renal arteries in the same group. Importantly, these hemodynamic changes evaluated by sonography preceded the rise of sCr levels. Sonography-based indices such as RI or PI can thus be useful predictive markers of declining renal function in rodents. From our sonography-based observations in the kidneys of rats that underwent AKI, we showed that these noninvasive hemodynamic measurements may consider as an accurate, sensitive and robust method in detecting early stage kidney dysfunction. This study also underscores the importance of ethical issues associated with animal use in research.

Early stage hemodynamic dysfunction is critical to the development of kidney disease. Yet, detection methodologies are limited. Recent advances in sonography provide a noninvasive, accurate option for early detection of kidney injury. This study outlines a step-by-step, sonographic methodology for detecting kidney dysfunction using a drug-induced nephrotoxicity rat model.

大鼠使用超声技术药物引起的肾血流动力学障碍的早期检测

The kidney normally functions to maintain hemodynamic homeostasis and is a major site of damage caused by drug toxicity. Drug-induced nephrotoxicity is ...

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.

A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.

心脏重构通过大鼠腹主动脉缩窄的模型

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and ...

Cardiac Magnetic Resonance for the Evaluation of Suspected Cardiac Thrombus: Conventional and Emerging Techniques

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques.&#160;The appearance of a mass on certain magnetic resonance (MR) sequences can help differentiate a thrombus from competing diagnoses such as a tumor. T1 and T2 signal characteristics of a thrombus are related to the evolution of hemoglobin properties. A thrombus typically does not enhance following contrast administration, which also helps differentiation from a tumor. We also highlight the emerging role of T1 mapping in the evaluation of a thrombus, which can add another level of support in diagnosis. Prior to any CMR exam, patient screening and interviews are critical to ensure safety and to optimize patient comfort. Effective communication during the exam between the technologist and the patient promotes proper breath holding technique and higher quality images. Volumetric post processing and structured reporting are helpful to ensure that the radiologist answers the ordering services&#39; question and communicates these results effectively. Optimal pre-MR safety evaluation, CMR exam execution, and post exam processing and reporting allow for delivery of high quality radiological service in the evaluation of a suspected cardiac thrombus.

The goal of this article is to describe how cardiac magnetic resonance can be used for the evaluation and diagnosis of a suspected cardiac thrombus. The method presented will describe data acquisition as well as the pre-procedure and post-procedure protocol.

心脏磁共振评估疑似心脏血栓:常规和新兴技术

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques.&#160;The ...

Echocardiographic Assessment of Cardiac Anatomy and Function in Adult Rats

The use of experimental animal models has become crucial in cardiovascular science. Most studies using rodent models are focused on two-dimensional imaging to study the cardiac anatomy of the left ventricle and M-mode echo to assess its dimensions. However, this could limit a comprehensive study. Herein, we describe a protocol that allows an assessment of the heart chamber size, left ventricular function (systolic and diastolic) and valvular function. A conventional medical ultrasound machine was used in this protocol and different echo views were obtained through left parasternal, apical and suprasternal windows. In the left parasternal window, the long and short axis were acquired to analyze left chamber dimensions, right ventricle and pulmonary artery dimensions, and mitral, pulmonary and aortic valve function. The apical window allows the measurement of heart chamber dimensions and evaluation of systolic and diastolic parameters. It also allows Doppler assessment with detection and quantification of heart valve disturbances (regurgitation or stenosis). Different segments and walls of the left ventricle are visualized throughout all views. Finally, the ascending aorta, aortic arch, and descending aorta can be imaged through the suprasternal window. A combination of ultrasound imaging, Doppler flow and tissue Doppler assessment have been obtained to study cardiac morphology and function. This represents an important contribution to improve the assessment of cardiac function in adult rats with impact for research using these animal models.

A non-invasive protocol for transthoracic echocardiography assessment of cardiac anatomy and function for adult rats is presented in the current study. The heart valves, all four cardiac chambers and the ascending aorta, aortic arch and descending aorta are studied in detail.

成人大鼠心脏解剖与功能的超声心动图评估

The use of experimental animal models has become crucial in cardiovascular science. Most studies using rodent models are focused on two-dimensional ...

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily and highly reproducible MI induction procedure is required to obtain further insight and better understanding of the underlying pathological changes. This procedure can also be used to evaluate the effects or potency of new and promising treatments (as drugs or interventions) in acute MI, subsequent remodeling and heart failure (HF). After intubation and pre-operative preparation of the animal, an anesthetic protocol with isoflurane was performed, and the surgical procedure was conducted&#160;quickly. Using a minimally invasive approach, the left anterior descending artery (LAD) was located and occluded by a ligature. The occlusion can be performed acutely for subsequent reperfusion (ischemia/reperfusion injury). Alternatively, the vessel can be ligated permanently to investigate the development of chronic MI, remodeling or HF. Despite common pitfalls, the drop-out rates are minimal. Various treatments such as remote ischemic conditioning can be examined for their cardioprotective potential pre-, peri- and post-operatively. The post-operative recovery was quick as the anesthesia was precisely controlled and the duration of the operation was short. Post-operative analgesia was administered for three days. The minimally invasive procedure reduces the risk of infection and inflammation. Furthermore, it facilitates rapid recovery. The &#8220;working heart&#8221; measurements were performed ex vivo and enabled precise control of preload, afterload and flow. This procedure requires specific equipment and training for adequate performance. This manuscript provides a detailed step-by-step introduction for conducting these measurements.

This article presents an efficient method to perform myocardial ischemia and subsequent chronic reperfusion in rats using a minimally invasive approach. In addition, left ventricular hemodynamic function of rats is assessed by echocardiography and isolated working heart methods.&#160;

诱导大鼠心肌梗死的半微创方法及独立工作心脏系统对心脏功能的评估

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily ...

Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training physicians&#39; wire-skills as well as improving planning of interventional procedures. The aim of this study was to develop a manufacturing process of patient-specific 3D-printed models for cardiovascular interventions.
To create a 3D-printed elastic phantom, different 3D-printing materials were compared to porcine biological tissues (i.e., aortic tissue) in terms of mechanical characteristics. A fitting material was selected based on comparative tensile tests and specific material thicknesses were defined. Anonymized contrast-enhanced CT-datasets were collected retrospectively. Patient-specific volumetric models were extracted from these datasets and subsequently 3D-printed. A pulsatile flow loop was constructed to simulate the intraluminal blood flow during interventions. Models&#39; suitability for clinical imaging was assessed by x-ray imaging, CT, 4D-MRI and (Doppler) ultrasonography. Contrast medium was used to enhance visibility in x-ray-based imaging. Different catheterization techniques were applied to evaluate the 3D-printed phantoms in physicians&#39; training as well as for pre-interventional therapy planning.
Printed models showed a high printing resolution (~30 &#181;m) and mechanical properties of the chosen material were comparable to physiological biomechanics. Physical and digital models showed high anatomical accuracy when compared to the underlying radiological dataset. Printed models were suitable for ultrasonic imaging as well as standard x-rays. Doppler ultrasonography and 4D-MRI displayed flow patterns and landmark characteristics (i.e., turbulence, wall shear stress) matching native data. In a catheter-based laboratory setting, patient-specific phantoms were easy to catheterize. Therapy planning and training of interventional procedures on challenging anatomies (e.g., congenital heart disease (CHD)) was possible.
Flexible patient-specific cardiovascular phantoms were 3D-printed, and the application of common clinical imaging techniques was possible. This new process is ideal as a training tool for catheter-based (electrophysiological) interventions and can be used in patient-specific therapy planning.

Here we present development of a mock circulation setup for multimodal therapy evaluation, pre-interventional planning, and physician-training on cardiovascular anatomies. With the application of patient-specific tomographic scans, this setup is ideal for therapeutic approaches, training, and education in individualized medicine.

干预规划和培训的3D打印心血管幻影的开发与评估

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training ...

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ineffective in many patients. To improve patient care, novel and innovative therapeutic concepts causally targeting arrhythmia mechanisms are needed. To study the complex pathophysiology of arrhythmias, suitable animal models are necessary, and mice have been proven to be ideal model species to evaluate the genetic impact on arrhythmias, to investigate fundamental molecular and cellular mechanisms, and to identify potential therapeutic targets.
Implantable telemetry devices are among the most powerful tools available to study electrophysiology in mice, allowing continuous ECG recording over a period of several months in freely moving, awake mice. However, due to the huge number of data points (&gt;1 million QRS complexes per day), analysis of telemetry data remains challenging. This article describes a step-by-step approach to analyze ECGs and to detect arrhythmias in long-term telemetry recordings using the software, Ponemah, with its analysis modules, ECG Pro and Data Insights, developed by Data Sciences International (DSI). To analyze basic ECG parameters, such as heart rate, P wave duration, PR interval, QRS interval, or QT duration, an automated attribute analysis was performed using Ponemah to identify P, Q, and T waves within individually adjusted windows around detected R waves. 
Results were then manually reviewed, allowing adjustment of individual annotations. The output from the attribute-based analysis and the pattern recognition analysis was then used by the Data Insights module to detect arrhythmias. This module allows an automatic screening for individually defined arrhythmias within the recording, followed by a manual review of suspected arrhythmia episodes. The article briefly discusses challenges in recording and detecting ECG signals, suggests strategies to improve data quality, and provides representative recordings of arrhythmias detected in mice using the approach described above.

Here we present a step-by-step protocol for a semiautomated approach to analyze murine long-term electrocardiography (ECG) data for basic ECG parameters and common arrhythmias. Data are obtained by implantable telemetry transmitters in living and awake mice and analyzed using Ponemah and its analysis modules.

分析长期心电图记录以检测小鼠心律失常

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ...

Analysis of Raw and Processed Cyperi Rhizoma Samples Using Liquid Chromatography-Tandem Mass Spectrometry in Rats with Primary Dysmenorrhea

Cyperi rhizoma (CR) is widely used in gynecology and is a general medicine for treating women's diseases in China. Since the analgesic effect of CR is enhanced after processing with vinegar, CR processed with vinegar (CRV) is generally used clinically. However, the mechanism by which the analgesic effect is enhanced by vinegar processing is unclear. In this study, the ultra-high pressure liquid chromatographytandem mass spectrometry (UPLC-MS/MS) technique was used to examine changes in the blood levels of the exogenous constituents and metabolites between CR-treated and CRV-treated rats with dysmenorrhea. The results revealed differing levels of 15 constituents and two metabolites in the blood of these rats. Among them, the levels of (-)-myrtenol and [(1R,2S,3R,4R)-3-hydroxy-1,4,7,7-tetramethylbicyclo[2.2.1]hept-2-yl]acetic acid in the CRV group were considerably higher than in the CR group. CRV reduced the level of 2-series prostanoids and 4-series leukotrienes with proinflammatory, platelet aggregation, and vasoconstriction activities and provided analgesic effects by modulating arachidonic acid and linoleic acid metabolism and the biosynthesis of unsaturated fatty acids. This study revealed that vinegar processing enhances the analgesic effect of CR and contributes to our understanding of the mechanism of action of CRV.

Here, a comparative analysis of raw and processed Cyperi rhizoma (CR) samples is presented using ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-MS/MS) in rats with primary dysmenorrhea. The changes in blood levels of the metabolites and the sample constituents were examined between rats treated with CR and CR processed with vinegar (CRV).

使用液相色谱-串联质谱分析原发性痛经大鼠的原始和加工的Cyperi Rhizoma样品

Cyperi rhizoma (CR) is widely used in gynecology and is a general medicine for treating women's diseases in China. Since the analgesic effect of CR is ...