小动物心脏骤停模型研制及影响复苏疗效相关因素的研究
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摘要
背景和目的：
由于临床研究受多种因素干扰，深入研究心脏骤停(Caridac arrest，CA)和心肺复苏(Cardiopulmonary resuscitation，CPR)的病理生理机制受到一定限制。动物实验的优势之一是能够严格控制各种混杂因素，使实验结果具有重复性，为研究疾病的发生机制、验证各种治疗药物或治疗手段创造了条件。由于小动物(如家兔、大鼠和小鼠等)的许多生理特性与大动物、甚至人类非常相似，采用小动物进行CPR的实验研究已经引起人们的广泛重视。
建立CA动物模型是进行CPR研究的前提条件。用交流电经右心室心内膜电击诱导大鼠和小鼠发生室颤是目前建立CA动物模型的主要方法。由于操作复杂，其应用受到限制。本研究的目的之一是寻找较为简便的、复制小动物室颤模型的方法。
心脏起搏在缓慢型心律失常的治疗中具有肯定的疗效，但在CPR中是否有效仍有争议。本研究的目的之二是观察经食道心脏起搏在窒息性CA大鼠CPR中的疗效，探讨其作用机制和影响因素。
药物在CPR中起重要作用。由于纳络酮和加压素在CPR中的疗效仍有争议，不同剂量的肾上腺素在大鼠CPR中的疗效如何尚未见有文献报导。本研究的目的之三是观察纳络酮和加压素在窒息性CA动物模型中的疗效，以及不同剂量加压素与肾上腺素对复苏疗效的影响，并对神经内分泌系统的变化与CPR疗效的关系进行探讨。
Background and objectives:
Due to interference of many factors in the clinical investigation, it is difficult to conduct a profound pathophysiologic study regarding cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). An advantage of animal models in CPR research is the ability to control differing variables that may be impractical to standardize in clinical trials, which provides an opportunity to testify different kinds of medications and treatments involved in CA and CPR. A lot of similarities can be found between small animals, such as rabbit, rat, mouse and so on, and large animals even human being. Therefore, an increasing number of small animals have been used in CPR experimental study.
To establish an animal model of CA is the key to conduct a CPR experimental study. Ventricular fibrillation is induced by alternating current delivered to right ventricular endocardium, which is the primary technique of establishment of animal model of CA in rat and in mouse currently. Unfortunately the manipulation is too difficult to practise in the most circumstance. One of the purposes of the study, therefore, is looking for more simple and convenient methods to establish an animal model of ventricular fibrillation in rat and in mouse.
由于临床研究受多种因素干扰，深入研究心脏骤停(Caridac arrest，CA)和心肺复苏(Cardiopulmonary resuscitation，CPR)的病理生理机制受到一定限制。动物实验的优势之一是能够严格控制各种混杂因素，使实验结果具有重复性，为研究疾病的发生机制、验证各种治疗药物或治疗手段创造了条件。由于小动物(如家兔、大鼠和小鼠等)的许多生理特性与大动物、甚至人类非常相似，采用小动物进行CPR的实验研究已经引起人们的广泛重视。
建立CA动物模型是进行CPR研究的前提条件。用交流电经右心室心内膜电击诱导大鼠和小鼠发生室颤是目前建立CA动物模型的主要方法。由于操作复杂，其应用受到限制。本研究的目的之一是寻找较为简便的、复制小动物室颤模型的方法。
心脏起搏在缓慢型心律失常的治疗中具有肯定的疗效，但在CPR中是否有效仍有争议。本研究的目的之二是观察经食道心脏起搏在窒息性CA大鼠CPR中的疗效，探讨其作用机制和影响因素。
药物在CPR中起重要作用。由于纳络酮和加压素在CPR中的疗效仍有争议，不同剂量的肾上腺素在大鼠CPR中的疗效如何尚未见有文献报导。本研究的目的之三是观察纳络酮和加压素在窒息性CA动物模型中的疗效，以及不同剂量加压素与肾上腺素对复苏疗效的影响，并对神经内分泌系统的变化与CPR疗效的关系进行探讨。
Background and objectives:
Due to interference of many factors in the clinical investigation, it is difficult to conduct a profound pathophysiologic study regarding cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). An advantage of animal models in CPR research is the ability to control differing variables that may be impractical to standardize in clinical trials, which provides an opportunity to testify different kinds of medications and treatments involved in CA and CPR. A lot of similarities can be found between small animals, such as rabbit, rat, mouse and so on, and large animals even human being. Therefore, an increasing number of small animals have been used in CPR experimental study.
To establish an animal model of CA is the key to conduct a CPR experimental study. Ventricular fibrillation is induced by alternating current delivered to right ventricular endocardium, which is the primary technique of establishment of animal model of CA in rat and in mouse currently. Unfortunately the manipulation is too difficult to practise in the most circumstance. One of the purposes of the study, therefore, is looking for more simple and convenient methods to establish an animal model of ventricular fibrillation in rat and in mouse.
引文
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1. Song L, Weil MH, Tang W, et al. Cardiopulmonary resuscitation in the mouse. J Appl Physiol. 2002; 93(4): 1222-1226.
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1. von Planta I, Weil MH, von Planta M, et al. Cardiopulmonary resuscitation in the rat. J Appl Physiol. 1988; 65(6): 2641-2647.
2．陈蒙华，刘唐威，谢露，等．老龄大鼠心室颤动动物模型的建立．中华老年心脑血管病杂志．2006；8(3)：208．
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1. Song L, Weil MH, Tang W, et al. Cardiopulmonary resuscitation in the mouse. J Appl Physiol. 2002;93(4): 1222-6.
2. Haugan K, Lain HR, Knudsen CB, et al. Atrial fibrillation in rats induced by rapid transesophageal atrial pacing during brief episodes of asphyxia: a new in vivo model. J Cardiovasc Pharmacol. 2004;44(1): 125-35.
3．陈蒙华，刘唐威，谢露，等．老龄大鼠心室颤动动物模型的建立．中华老年心脑血管病杂志．2006；8(3)：208．
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6. Cummins RO, Graves JR, Larsen MP, et al. Out-of-hospital transcutaneous pacing by emergency medical technicians in patients with asystolic cardiac arrest. N Engl J Med. 1993; 328(19): 1377-1382.
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9. Olson CM, Jastremski MS, Smith RW, et al. External cardiac pacing for out-of-hospital bradyasystolic arrest. Am J Emerg Med. 1985; 3(2): 129-131.
10. Zoll PM, Zoll RH, Falk RH, et al. External noninvasive temporary cardiac pacing: clinical trials. Circulation. 1985; 71 (5): 937-944.
11. O'Toole KS, Paris PM, Heller MB, et al. Emergency transcutaneous pacing in the management of patients with bradyasystolic rhythms. J Emerg Med. 1987; 5(4): 267-273.
12. Tachakra SS, Jepson E, Beckett MW, et al. Successful transcutaneous external pacing for asystole following cardiac arrest. Arch Emerg Med. 1988; 5(3): 184-185.
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1. Zoll PM: Resuscitation of the heart in ventricular standstill by external electric stimulation. New Eng J Med. 1952; 247(20):768-771.
2. ZOLL PM, LINENTHAL AJ, NORMAN LR.. Treatment of Stokes-Adams disease by external electric stimulation of the heart. Circulation. 1954; 9(4):482-493.
3. ZOLL PM, LINENTHAL AJ, NORMAN LR, et al. Treatment of the unexpected cardiac arrest by external electric stimulation of the heart. New Eng J Med. 1956; 254(12): 541-546.
4. ZOLL PM, LINENTHAL AJ, NORMAN LR, et al. External electric stimulation of the heart in cardiac arrest: Stokes-Adams disease, reflex vagal standstill, drug-induced standstill, and unexpected circulatory arrest. AMA Arch Intern Med. 1955; 96(5): 639-653.
5. Austin JL, Preis LK, Crampton RS, et al. Analysis of pacemaker malfunction and complications of temporary pacing in the coronary care unit. Am J Cardiol. 1982; 49(2): 301-306.
6. Hynes JK, Holmes DR Jr, Harrison CE. Five-year experience with temporary pacemaker therapy in the coronary care unit. Mayo Clin Proc. 1983; 58(2): 122-126.
7. Clinton JE, Zoll PM, Zoll R, et al. Emergency noninvasive external cardiac pacing. J Emerg Med. 1985; 2(3): 155-162.
8. White JD, Brown CG. Immediate transthoracic pacing for cardiac asystole in an emergency department setting. Am J Emerg Med. 1985; 3(2): 125-128.
9. Olson CM, Jastremski MS, Smith RW, et al. External cardiac pacing for out-of-hospital bradyasystolic arrest. Am J Emerg Med. 1985; 3(2): 129-131.
10. Zoll PM, Zoll RH, Falk RH, et al. External noninvasive temporary cardiac pacing: clinical trials. Circulation. 1985; 71(5): 937-944.
11. O'Toole KS, Paris PM, Heller MB, et al. Emergency transcutaneous pacing in the management of patients with bradyasystolic rhythms. J Emerg Med. 1987; 5(4): 267-273.
12. Tachakra SS, Jepson E, Beckett MW, et al. Successful transcutaneous external pacing for asystole following cardiac arrest. Arch Emerg Med. 1988; 5(3): 184-185.
13. Falk RH, Zoll PM, Zoll RH. Safety and efficacy of noninvasive cardiac pacing. A preliminary report. N Engl J Med. 1983; 309(19): 1166-1168.
14. Eitel DR, Guzzardi LJ, Stein SE, et al. Noninvasive transcutaneous cardiac pacing in prehospital cardiac arrest. Ann Emerg Med. 1987; 16(5): 531-534.
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18. Quan L, Graves JR, Kinder DR, et al. Transcutaneous cardiac pacing in the treatment of out-of-hospital pediatric cardiac arrests. Ann Emerg Med. 1992; 21(8): 905-909.
19. Cummins RO, Groves JR, Larsen MP, et al. Out-of-hospital transcutaneous pacing by emergency medical technicians in patients with asystolic cardiac arrest. N Engl J Med. 1993; 328(19): 1377-1382.
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24. Chase PB, Kern KB, Sanders AB, et al. Effects of graded doses of epinephrine on both noninvasive and invasive measures of myocardial perfusion and blood flow during cardiopulmonary resuscitation. Crit Care Med. 1993; 21(3): 413-419.
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