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Medicine

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

doi: 10.3791/2726 Published: April 5, 2011

Summary

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。

Abstract

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 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 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。

Protocol

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Discussion

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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。

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Disclosures

我们什么都没有透露。

Acknowledgments

这项研究是由授予美国公民在癫痫(治愈)研究的SLB支持。

References

  1. Chugh, S. S. Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease: The Oregon sudden unexpected death study. Circulation. 119, 663-670 (2009).
  2. Darbar, D. Sensitivity and specificity of QTc dispersion for identification of risk of cardiac death in patients with peripheral vascular disease. BMJ. 312, 874-878 (1996).
  3. Bruyne, M. C. de QTc dispersion predicts cardiac mortality in the elderly: The Rotterdam study. Circulation. 97, 467-472 (1998).
  4. Malik, M. Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation. 93, 1043-1065 (1996).
  5. Grippo, A. J. Increased susceptibility to ventricular arrhythmias in a rodent model of experimental depression. Am. J. Physiol. 286, H619-H626 (2004).
  6. Li, M., Wang, J., Xie, H. H., Shen, F. M., Su, D. F. The susceptibility of ventricular arrhythmia to aconitine in conscious hypertensive rats. Acta. 28, 211-215 (2007).
  7. Beig, M. I. Voluntary exercise does not affect stress-induced tachycardia, but improves resistance to cardiac arrhythmias in rats. Clin. Exp. Pharm. Physiol. Forthcoming (2010).
  8. Hazari, M. S., Haykai-Coates, N., Winsett, D. W., Costa, D. L., Farraj, A. K. A single exposure to particulate or gaseous ari pollution increases the risk of aconitine-induced cardiac arrhythmia in hypertensive rats. Toxicol. Sci. 112, 532-542 (2009).
  9. Amran, M. S., Hashimoto, K., Homma, N. 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. J. Pharmacol. Exp. Ther. 310, 83-89 (2004).
  10. Klekot, A. A. Antiarrhythmic activity of a membrane-protecting agent Sal'magin in rats with aconitine-induced arrhythmias. Bull. Exp. Biol. Med. 142, 209-211 (2006).
  11. Lowenstein, D. H., Alldredge, B. K. Status Epilepticus. New England J. Med. 338, 970-976 (1998).
  12. Walker, M. Status epilepticus: an evidence based guide. BMJ. 331, 673-677 (2005).
  13. Shorvon, S. Status epilepticus: its clinical features and treatment in children and adults. Cambridge University Press. (1994).
  14. Boggs, J. G. Hemodynamic monitoring prior to and at the time of death in status epilepticus. Epilepsy Res. 31, 199-209 (1998).
  15. Walton, N. Y. Systemic effects of generalized convulsive status epilepticus. Epilepsia. 34, Suppl 1. S54-S58 (1993).
  16. Boggs, J. G., Painter, J. A., DeLorenzo, R. J. Analysis of electrocardiographic changes in status epilepticus. Epilepsy Res. 14, 87-94 (1993).
  17. Painter, J. A., Shiel, F. O., DeLorenzo, R. J. Cardiac pathology findings in status epilepticus. Epilepsia. 34, Suppl 6. 30-30 (1993).
  18. Lathers, C. M., Schraeder, P. L. Clinical pharmacology: drugs as a benefit and/or risk in sudden unexpected death in epilepsy. J. Clin. Pharmacol. 42, 123-126 (2002).
  19. Dashieff, R. M. Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and specualtion of the relationship to sudden cardiac death. J. Clin. Neurophysiol. 8, 216-222 (1991).
  20. Tigaran, P. -C. odrea, Dalager-Pedersen, S., Baandrup, S., Dam, U., M,, Vesterby-Charles, A. Sudden unexpected death in epilepsy: is death by seizures a cardiac event. Am. J. Forensic Med. Pathol. 26, 99-105 (2005).
  21. Leung, H., Kwan, P., Elger, C. E. Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy. Epilepsy and Behavior. 9, 19-30 (2006).
  22. Nei, M. EEG and ECG in sudden unexplained death in epilepsy. Epilepsia. 45, 338-345 (2004).
  23. Dudek, F. E., Clark, S., Williams, P. A., Grabenstatter, H. L. Models of Seizures and Epilepsy. Pitkanen, A., Schwartzkroin, P. A., Moshe, S. L. Elsevier. 415-432 (2006).
  24. Turski, W. A. Limbic seizures produced by pilocarpine in rats: behavioral electroencephalographic, and neuropathological study. Behav. Brain Res. 9, 315-335 (1989).
  25. Kulkarni, S. K., George, B. Lithium-pilocarpine neurotoxicity: a potential model of status epilepticus. Methods Find. Exp. Clin. Pharamacol. 17, 551-567 (1995).
  26. Stein, P. K., Bosner, M. S., Kleiger, R. E., Conger, B. M. Hart rate variability: a measure of cardiac autonomic tone. Am. Heart J. 127, 1376-1381 (1994).
  27. Metcalf, C. S., Poelzing, S., Little, J. G., Bealer, S. L. Status epilepticus induces cardiac myofilament damage and increased susceptibility to arrhythmias in rat. Am. J. Physiol. 297, H2120-H2127 (2009).
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
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Bealer, S. L., Metcalf, C. S., Little, J. G. Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus. J. Vis. Exp. (50), e2726, doi:10.3791/2726 (2011).More

Bealer, S. L., Metcalf, C. S., Little, J. G. Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus. J. Vis. Exp. (50), e2726, doi:10.3791/2726 (2011).

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