β-肾上腺素受体兴奋剂对布比卡因致心肌毒性的影响

发布时间：2018-03-03 18:38

本文选题：β-肾上腺素受体兴奋剂　切入点：异丙肾上腺素　出处：《河北医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：第一部分β-肾上腺素受体兴奋剂对布比卡因中毒心肌心电图的影响目的:儿茶酚胺因其增加舒张压和冠状动脉灌注压常作为治疗心脏衰竭的一线用药;但是,肾上腺素不但不能改善,反而会加重布比卡因引起的心脏功能不全,甚至引起肺水肿。在前期研究中,本课题组已经在单个心肌细胞水平证实了异丙肾上腺素可加重布比卡因致心肌收缩抑制,而艾司洛尔能逆转这一作用。本实验将检测β-肾上腺素受体兴奋剂对布比卡因中毒心肌的自律性与传导能力的影响。方法:动物模型成年雄性SD大鼠,体重200~250g。大鼠经10%水合氯醛(0.3ml/100g)腹腔注射麻醉。经尾静脉建立静脉液体通路后,将大鼠仰卧位固定并连接心电图。心电图的探针分别固定于大鼠肢体末端:红色探针固定于左下肢,绿色探针固定于右上肢,黑色探针固定于右下肢。这种连接方式采集到的是心电图Ⅱ导联波形。所有大鼠实验过程中保持自主呼吸。利用RM6420系列多道生理信号采集处理系统采集心电图并呈现于显示仪上。实验分组将大鼠采用随机数字方法分为3组:布比卡因+生理盐水组、布比卡因+异丙肾上腺素组、布比卡因+肾上腺素组。每组观察7只大鼠。给药过程布比卡因+生理盐水组:经尾静脉匀速给予布比卡因0.75mg/kg/min,持续时间为12min40s;随后匀速给予生理盐水0.4ml,持续时间为1min30s。布比卡因+异丙肾上腺素组:经尾静脉匀速给予布比卡因0.75mg/kg/min,持续时间为12min40s;随后匀速给予异丙肾上腺素(0.08mg/kg,0.4ml),持续时间为1min30s。布比卡因+肾上腺素组:经尾静脉匀速给予布比卡因0.75mg/kg/min,持续时间为12min40s;随后匀速给予肾上腺素(6μg/kg,0.4ml),持续时间为1min30s。由RM6420系列多道生理信号采集处理系统监测大鼠心电图并分析记录PR间期、QRS间期和心率等指标。结果:1布比卡因抑制心肌传导功能;布比卡因中毒心肌可出现PR间期延长、QRS间期增宽,心率下降(P0.05);2异丙肾上腺素(0.08mg/kg)、肾上腺素(6μg/kg)对布比卡因中毒后心肌PR间期和QRS间期无明显影响。在静脉输注1min时,两组中毒心肌心率增快(P0.05),而在实验后期与对照组无差异。第二部分β-肾上腺素受体兴奋剂加重布比卡因对心肌力学的抑制作用目的:布比卡因中毒在临床中并不常见但严重影响患者生命。儿茶酚胺类药物是治疗心脏功能衰竭的一线用药。然而,肾上腺素对于解救布比卡因引起的心脏毒性疗效不佳。本课题组在前期研究中采用可视化动缘探测系统动态跟踪同步检测技术,观察检测了异丙肾上腺素和艾司洛尔对布比卡因致单心肌细胞收缩功能抑制的影响。结果显示,布比卡因呈浓度依赖性可逆的抑制心肌细胞收缩功能,异丙肾上腺素可以加重布比卡因抑制心肌细胞收缩的毒性作用,而艾司洛尔可以逆转此恶化作用。本实验将在活体动物中检验β-肾上腺素受体兴奋剂在布比卡因致心肌力学抑制中的影响。方法:动物模型成年SD大鼠,雄性,体重200g~250g。在10%的水合氯醛(0.3ml/100g)腹腔注射麻醉后,取仰卧位,经尾静脉建立静脉液体通路。经颈总动脉插管并连接于RM6420系列多道生理信号采集处理系统,用于测定心室内压,波形记录于显示器上。实验分组采用随机数字方法将大鼠分为3组:布比卡因+生理盐水组、布比卡因+异丙肾上腺素组、布比卡因+肾上腺素组。每组观察7只大鼠。给药过程布比卡因+生理盐水组:经尾静脉匀速给予布比卡因0.75mg/kg/min,持续时间为12min40s;随后匀速给予生理盐水0.4ml,持续时间为1min30s。布比卡因+异丙肾上腺素组:经尾静脉匀速给予布比卡因0.75mg/kg/min,持续时间为12min40s;随后匀速给予异丙肾上腺素(0.08mg/kg,0.4ml),持续时间为1min30s。布比卡因+肾上腺素组:经尾静脉匀速给予布比卡因0.75mg/kg/min,持续时间为12min40s;随后匀速给予肾上腺素(3μg/kg,0.4ml),持续时间为1min30s。观察记录实验指标:给药过程中,分析并记录心室收缩压(left ventricular systolic pressure,LVSP)、心室舒张末压(left ventricular end-diastolic pressure,LVEDP)、左心室内压最大上升速率(+dp/dt max)、左心室内压最大下降速率(-dp/dt max)等指标。结果:1布比卡因抑制心肌力学,出现LVSP下降、LVEDP上升、+dp/dt max下降、-dp/dt max下降,且结果有统计学意义(P0.05)。2β-肾上腺素受体兴奋剂异丙肾上腺素、肾上腺素可加重布比卡因对心肌力学的抑制作用,出现LVSP下降、+dp/dt max下降,且上述变化均有统计学意义(P0.05);而对LVEDP、-dp/dt max未见明显影响。结论1布比卡因抑制大鼠心肌传导功能和心肌力学;2β-肾上腺素能受体兴奋剂可加重布比卡因致大鼠心肌力学抑制,提高布比卡因中毒心肌自律性,但对传导功能无明显作用。
[Abstract]:The first part of the beta adrenergic receptor stimulant of bupivacaine intoxication Objective: ECG myocardial catecholamines due to the increase in diastolic blood pressure and coronary perfusion pressure is often used as a first-line treatment of heart failure; however, epinephrine could improve heart function, it will increase the bupivacaine induced incomplete, even cause pulmonary edema. In previous studies, the research group has confirmed that isoproterenol induced myocardial contraction of bupivacaine can aggravate the inhibition in the level of single cells, and esmolol can reverse this effect. This experiment will affect the self detection of beta adrenoceptor stimulants on bupivacaine and poisoning with myocardial conduction ability. Methods: the animal model of adult male SD rats 10% chloral hydrate by weight of 200~250g. rats (0.3ml/100g) intraperitoneal injection of anesthesia via the tail vein. The establishment of intravenous fluid pathway, the In the supine position fixed and connected. The electrocardiogram ECG probe are respectively fixed on the end of limbs in rats: Red probe fixed on the left lower extremity, green probe fixed to the right upper limb, black probe fixed to the right lower limb. This connection is collected cardiograph waveform. Maintain autonomous breathing in all rats during the experiment using RM6420. A series of multi-channel physiological signal acquisition and processing system of ECG acquisition and presentation on display. Experimental group rats were randomly into 3 groups: bupivacaine + saline + Bupivacaine group, isoproterenol group, bupivacaine and epinephrine group. Each group were 7 rats. Administration of bupivacaine + saline group: intravenous administration of bupivacaine at 0.75mg/kg/min, duration of 12min40s; then the uniform saline 0.4ml, duration 1min30s. bupivacaine + isoproterenol Epinephrine group: intravenous administration of bupivacaine at 0.75mg/kg/min, duration of 12min40s; then the uniform administration of isoprenaline (0.08mg/kg, 0.4ml), duration of 1min30s. bupivacaine and epinephrine group: intravenous administration of bupivacaine 0.75mg/kg/ constant min, duration of 12min40s; then the uniform administration of epinephrine (6 g/kg, 0.4ml). For the duration of 1min30s. by RM6420 series of multi-channel physiological signal acquisition and processing system of ECG monitoring in rats and analysis of PR interval, QRS interval and heart rate. Results: 1 bupivacaine for inhibiting myocardial conduction function; myocardial bupivacaine intoxication can occur with prolonged PR interval, QRS interval widened, heart rate decreased 2 (P0.05); isoproterenol (0.08mg/kg), epinephrine (6 g/kg) had no obvious effect on bupivacaine intoxication after myocardial PR and QRS intervals. After intravenous infusion of 1min, two groups of myocardial poisoning Heart rate (P0.05), and later in the experiment no difference with the control group. The second part of the beta adrenergic receptor stimulant increase inhibitory effect of bupivacaine on myocardial mechanics Objective: bupivacaine intoxication in clinic is not common but serious impact on the lives of patients. Catecholamine drugs as first-line agents in treatment of heart failure. However, for epinephrine effect of bupivacaine induced cardiac toxicity to rescue the poor. The previous studies using visual motion edge detection system of dynamic tracking synchronization detection technology to detect isoproterenol and effect of esmolol single myocardial cell contraction function on inhibition of bupivacaine induced by bupivacaine. The results showed that the contraction of myocardial cell concentration dependent reversible inhibition function the toxic effects of isoproterenol, bupivacaine can aggravate the inhibition of myocardial cell contraction, and AI division Los You can reverse this deterioration effect. This experiment will test the beta adrenergic receptor in the effect of doping of bupivacaine in inhibiting myocardial mechanics in vivo animal. Methods: the animal model of adult SD rats, male, weight 200g~250g. of 10% chloral hydrate (0.3ml/100g) intraperitoneal injection of anesthesia, supine position, the tail the establishment of vein intravenous fluid pathway. The common carotid artery and connected to the RM6420 series of multi-channel physiological signal collecting and processing system for the determination of ventricular pressure waveforms, recorded on display. Experimental groups by using random number method the rats were divided into 3 groups: bupivacaine + bupivacaine + saline group, isoproterenol group, bupivacaine + epinephrine group. 7 rats of each group were observed. Administration of bupivacaine + saline group: intravenous administration of bupivacaine at 0.75mg/kg/min, duration of 12min40s; then give uniform Physiological saline 0.4ml, duration 1min30s. bupivacaine + isoproterenol group: intravenous administration of bupivacaine at 0.75mg/kg/min, duration of 12min40s; then the uniform administration of isoprenaline (0.08mg/kg, 0.4ml), duration of 1min30s. bupivacaine and epinephrine group: intravenous administration of bupivacaine at 0.75mg/kg/min, duration of 12min40s and uniform; epinephrine (3 g/kg, 0.4ml), duration of 1min30s. observed experimental indicators: administration process, analysis and record the ventricular systolic pressure (left ventricular systolic pressure, LVSP), left ventricular end diastolic pressure (left ventricular end-diastolic pressure, LVEDP), left ventricular pressure maximal rate of rise (+dp/dt max). Left ventricular pressure decline rate (-dp/dt max) and other indicators. Results: 1 bupivacaine inhibits myocardial mechanics, LVSP decreased, LVEDP increased, +d P/dt Max -dp/dt decreased, Max decreased, and the results are statistically significant (P0.05).2 beta adrenergic receptor stimulant isoproterenol and epinephrine can increase the inhibitory effect of bupivacaine on myocardial mechanics, LVSP decreased, +dp/dt Max decreased, and the changes were statistically significant (P0.05); while the LVEDP, Max was -dp/dt obvious effect. Conclusion 1 bupivacaine inhibits myocardial conduction function and myocardial mechanics in rats; 2 beta adrenergic receptor agonists can aggravate myocardial mechanics in rats induced by bupivacaine inhibited, improve myocardial bupivacaine self-discipline, but no obvious effect on the conduction function.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R965

【参考文献】