电刺激兔下丘脑不同部位诱发的房性心律失常

在57只麻醉家兔,用同心圆双极电极刺激右侧下丘脑外侧区、前区、后区、背内侧核、腹内侧核五个不同部位,观察到均能诱发房性早搏等房性心律失常,且存在相对特异性。在用1mA 强度电刺激时,以前三个部位的诱发率较高。如预先轻度灼伤右心房后再刺激下丘脑外侧区或前区,可显著提高房性心律失常的发生率,并使诱发房颤等严重房性心律失常的机会有所增加。在同时描记股动脉血压的家兔中,观察到房性心律失常均在血压增高时出现,并以下丘脑后区、前区、外侧区的增压反应较为显著。在下丘脑外侧区增加刺激强度时,房性心律失常的发生率不随增压平均值的增加而递增,与室性心律失常不同。切断双侧颈迷走神经干后再刺激下丘脑同一部位时,原能诱发房性早搏的家兔全部不再诱发,而原能诱发以室性早搏为主的室性心律失常的部分兔仍能发生。这些结果提示,电刺激下丘脑诱发房性心律失常的机制与室性心律失常有所不同。     

缓冲神经在刺激兔下丘脑诱发室性期前收缩中的作用

1.静脉注射氰化钾(0.3mg/kg)可引起血压升高和室性心律失常,并能使刺激下丘脑诱发的室性期前收缩增多。去除双侧窦神经后,上述现象消失。2.刺激降压神经时,刺激下丘脑诱发的室性期前收缩显著减少。3.切断双侧缓冲神经后短时内,刺激下丘脑诱发的室性期前收缩极度增多,并且不易被躯体传入冲动所抑制。二小时后,这种室性期前收缩减少,且可为刺激腓深神经所抑制。4.电刺激延髓中线区不仅可以降低血压,而且能减弱刺激下丘脑诱发的升压反应、抑制刺激下丘脑诱发的室性期前收缩。损毁该区后,刺激腓深神经不再能抑制刺激下丘脑诱发的室性期前收缩。5.上述结果表明:化学感受性反射能易化刺激下丘脑诱发的室性期前收缩,而压力感受性反射可以抑制这种室性期前收缩,但躯体传入冲动对这种心律失常的抑制作用并不依赖于缓冲神经的存在,而有赖于延髓中线核群的完整性。     

电刺激杏仁复合体诱发心律失常及其下行神经通路的初步探讨

电刺激杏仁复合体能诱发心律失常。心律失常的类型为心动过缓伴室性或结性期外收缩。刺激杏仁复合体不同亚核均能诱发心律失常,不同类型的心律失常在核内具有相应的代表点。心律失常发作与杏仁局部区域诱发的爆发性后放电有关。推测杏仁复合体内神经元过度激活可能通过杏仁-迷走神经运动背核及杏仁-下丘脑外侧区等通路下行,使心率减慢、房室传导阻滞而导致心律失常。     

刺激兔下丘脑诱发的防御反应和室性期前收缩

电刺激兔下丘脑近中线区可以引起血压升高、肢体血流量增多、内脏血流量减少、瞳孔扩大和呼吸急促、鼻翼扇动、四肢爬动等一系列类似于猫发生防御反应时的植物、躯体性反应,但其中肢体血流增多反应不能为阿托品所阻断。在出现上述反应的同时可出现心交感活动亢进、产生室性期前收缩等心律失常。摘除双侧星状神经节后,刺激下丘脑诱发的室性期前收缩(HVE)几乎消失,升压反应也减弱。在颈部切断双侧迷走神经可使 HVE 增多、升压反应增强,静脉注射阿托品(0.2mg/kg)不产生 HVE 增多和升压反应增强的效应。根据上述结果,可以认为兔下丘脑也存在着“防御反应区”,HVE 主要是兴奋了防御反应区造成心交感活动亢进所致。迷走神经对 HVE 有抑制作用,其效应可能与传入纤维的活动有关。     

刺激兔下丘脑室旁核诱发的心律失常与增压反应

在60只局麻与肌松剂制动的家兔,观察到用0.1—0.4mA,50Hz,1ms 的方波电刺激下丘脑室旁核(PV)能诱发频发性心律失常(包括室性与室上性期前收缩)及显著的动脉血压升高。与同侧的下丘脑外侧区(LHA)及腹内侧核(VMH)相比,刺激PV诱发期前收缩的次数更为频繁,增压反应幅度较大,且所需阈值亦较低。较低强度刺激LHA 在部分兔能引起血压下降与心率减慢,而PV 则一致地诱发增压反应。电刺激腓深神经能抑制刺激PV诱发的期前收缩,但在中脑中央灰质微量注射吗啡或电解毁损只能完全阻断刺激VMH诱发的期前收缩,而不能完全阻断PV诱发的期前收缩。这些结果提示,PV是下丘脑中诱发心律失常与血压增高的高反应区之一,并且可能具有不同于LHA或VMH的神经机制或下行神经通路。     

刺激兔下丘脑对心肌局部血流量和脊髓中间外侧柱P物质含量的影响

本工作在48只氯醛糖-尿酯混合液静脉麻醉,三碘季铵酚制动,人工呼吸,切断两侧迷走神经,并静脉注射心得安(15mg/kg)阻断 β 受体的兔上进行。实验结果显示:1.电刺激下丘脑背内侧核(DMH),可观察到平均动脉血压(MABP)增加,心率无明显变化。用放射性生物微球技术测定心肌局部血流量(RMBF),看到刺激左侧或右侧 DMH 均使左室 RMBF 明显减少,前者减少20.9%,而后者减少13.2%,两者相比差异有显著性(p<0.05),但右室RMBF 改变不明显。2.左侧或右侧 DMH 刺激使左室前壁心外膜电图(EECG)ST 段明显抬高,EECG-ST 段变化与 RMBF 呈负相关(r=-0.825,p<0.01),但与血压变化呈非线性相关(r=0.347,p=0.159)3.用放射免疫测定技术(RIA)测定脊髓胸2-5(T_(2-5))节段中间外侧柱(IML)中 P 物质(SP)含量,观察到在刺激 DMH 诱发心肌缺血的动物中,两侧IML 内 SP 的含量均显著减少,以刺激的同侧 IML 时变化更明显。上述结果提示:下丘脑背内侧核兴奋可诱发冠状动脉痉挛,心肌局部血流量减少,其中枢机理可能与脊髓 IML 部位 SP 释放,诱发交感缩冠脉作用有关。     

刺激兔下丘脑近中线区对心功能的影响

1.刺激兔下丘脑近中线区可出现血压、左内压上升、瞳孔扩大以及一系列驱体运动等类似于发生防御反应的现象,间有心律失常出现。反复刺激之,可导致心输出量减少,心肌缺血等心功能损害。2.刺激下丘脑近中线区时出现的窦性心动过缓、窦房暂停等与迷走神经的作用有关。而过早搏动则与交感兴奋对心肌β受体的作用以及血压升高、心室负荷骤然增高的关系较为密切。3.反复刺激下丘脑近中线区所引起的心肌缺血、心输出量减少等。心功能损害主要与儿茶酚胺对心肌β受体的刺激有关。     

躯体传入冲动对刺激兔下丘脑诱发期前收缩的抑制作用

1.以低频、低强度方波刺激腓深神经或正中神经可以抑制由刺激下丘脑引起的期前收缩。若电刺激过强或刺激腓浅、挠浅、前臂外侧皮神经则无此作用。2.刺激躯体神经对期前收缩的抑制作用与迷走神经及心室后负荷无密切关系,很可能是通过抑制心交感中枢紧张性来实现的。3.刺激下丘脑诱发的期前收缩可为中央灰质内微量注入吗啡所抑制,而为微量注入纳洛酮所增多,微量注入纳洛酮并可阻断躯体传入冲动对期前收缩的抑制作用。表明此种抑制作用有脑内鸦片受体与吗啡样物质参与。     

躯体传入冲动抑制中枢性心肌缺血的脊髓机制

本工作在58只尿酯-氯醛糖麻醉,三碘季铵酚制动,人工呼吸,切断迷走神经的兔上进行。结果显示:电刺激正中神经(MN)和腓深神经(DPN)均能抑制或部分抑制下丘脑背内侧核(DMH)诱发的缺血性心电 ST 段偏移,以刺激 MN 的抑制作用更为明显。蛛网膜下腔注射(ith)吗啡(40μg)也能抑制这种缺血性心电变化。ith 纳洛酮(20μg)则可阻断刺激 MN 对中枢性心肌缺血的抑制作用。完整兔在刺激左侧 MN 或 DPN 后,用放射免疫技术测得胸 2—5(T_2-5)节段两侧中间外侧柱(IML)中亮氨酸脑啡肽(LENK)含量明显增加。在颈1(C_1)水平横断脊髓,以同样参数刺激左侧 MN,同侧胸髓 IML 中 LENK 含量明显增加,而对侧胸髓 IML 中 LENK 含量无明显改变;刺激一侧 DPN,T_(2-5)的两侧 IML 中 LENK 含量均无明显变化。上述结果表明,刺激 MN 与 DPN 均能抑制 DMH 诱发的中枢性心肌缺血,但以MN 作用较明显。我们推测这种抑制作用可能与通过脊上机制双侧性增加 IML 中 LENK 含量有关,MN 的抑制作用可能尚包括直接激活胸髓内的脑啡肽系统,增加同侧 IML 中 LENK含量,加强了对交感输出活动的抑制作用。     

内源性一氧化氮在高血压心肌肥厚中的作用

目的和方法：本实验用Ｌ精氨酸和一氧化氮合酶（ＮＯＳ）抑制剂ＬＮＡＭＥ观察内源性一氧化氮（ＮＯ）在高血压性心肌肥厚中的作用。结果：腹主动脉缩窄引起大鼠动脉血压显著升高,左心室重量／体重比值显著增加,左心室ＮＯ含量显著下降;Ｌ精氨酸不影响主动脉缩窄大鼠动脉血压,但减轻左心室重量／体重比值,明显升高左心室ＮＯ含量,加入ＬＮＡＭＥ可消除Ｌ精氨酸的上述作用;主动脉缩窄大鼠给予ＬＮＡＭＥ,动脉血压和左心室／体重比值并没有进一步增加;假手术大鼠给予ＬＮＡＭＥ,血压明显升高,左心室重量／体重比值轻度增加;主动脉缩窄大鼠不论是服用Ｌ精氨酸还是ＬＮＡＭＥ,左心室ｃＧＭＰ含量都明显增加。结论：口服Ｌ精氨酸可减轻主动脉缩窄大鼠心肌肥厚但不影响动脉血压,此作用可能是通过Ｌ精氨酸ＮＯ途径实现的,与ｃＧＭＰ机制无关。     

The effect of afterload on the cardiodepressor reflex response to coronary artery occlusion in dogs

The acute hemodynamic responses to anterior and posterior wall ischemia were examined at different afterloads in 30 open-chest anaesthetized dogs. Regional and global left ventricular responses to acute ischemia were also measured before and following bilateral cervical vagotomy in 18 dogs. As the preocclusion afterload (mean aortic pressure) was progressively raised with intravenous methoxamine, a significant decrease in stroke volume occurred following circumflex artery occlusion, whereas no change in stroke volume occurred following occlusion of the left anterior descending artery. Bilateral cervical vagotomy completely inhibited the decrease in stroke volume during circumflex occlusion at high afterload. Vagotomy had no effect on the hemodynamic response to acute anterior wall ischemia. Reversible cold vagal block in paced hearts at high afterload unmasked compensatory inotropy in the nonischemic anterior myocardial segment during circumflex occlusion. Restoring vagal tone by rewarming attenuated the fractional shortening of the nonischemic segment. The results indicate that a relationship exists between myocardial wall tension and reflex cardioinhibition during acute posterior wall but not anterior wall ischemia in dogs.     

第四脑室注射吗啡对应激性高血粘度与血压升高的影响

实验用Wistar大鼠99只,雄性250g左右,随机分三组:对照组、悬吊加束缚组、悬吊一束缚加电针组。结果:(1)清醒大鼠束缚加悬吊可引起应激性高血粘度和血压升高,切断双侧颈迷走神经后上述现象仍存在。静脉注射心得安(0.3mg/ml)或酚妥拉明(0.3 mg/ml)对正常大鼠血压、血粘度影响不大,但对应激性血压升高均有抑制作用。静脉注射心得安还可降低应激性高血粘度。(2)电针大鼠右后肢对应激性高血粘度和血压升高有抑制作用。(3)第四脑室内注射吗啡(10μg/10 μl)15或30min后可降低应激性高血粘度和血压升高,注入等量生理盐水无变化。若在第四脑室注射纳洛酮 (10μg/10μl)则可部分阻断电针右后肢对悬吊-束缚诱发的高血粘度和血压升高的抑制作用。结果提示:悬吊-束缚大鼠可能兴奋交感神经传出系统经激活β受体诱发应激性高血粘度阻断α或β受体可降低应激性血压升高。脑内阿片肽可抑制应激性高血粘度和血压升高,脑内河片肽受体的激活可参与电针后肢对应激性高血粘度和血压升高的抑制作用。     

EDRF对PE引起的大鼠主动脉缩血管效应的作用

本文研究ＥＤＲＦ（ｅｎｄｏｔｈｅｌｉｕｍ－ｄｅｒｉｖｅｄｒｅｌａｘｉｎｇｆａｃｔｏｒ,ＥＤＲＦ）对ＰＥ（ｐｈｅｎｙｌｅｐｈｒｉｎｅ）引起的大鼠主动脉收缩反应的影响。内皮完整和去内皮的大鼠主动脉环悬挂于器官浴槽中,测定血管的张力和收缩速度的变化。所有的实验在消炎痛（ｉｎｄｏｍｅｔｈａｃｉｎ,１０μｍｏｌ／Ｌ）存在下进行。用美兰（ｍｅｔｈｙｌｅｎｅｂｌｕｅ,ＭＢ,１０μｍｏｌ／Ｌ）或左旋硝基精氨酸（ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ,Ｌ－ＮＮＡ,３０μｍｏｌ／Ｌ）处理内皮完整的大鼠主动脉环,ＰＥ的剂量－收缩张力曲线明显左移,ＥＣ３０值均降低５倍,最大反应比率分别为１．６±０．４和１．６±０．５。在去内皮的大鼠主动脉环中,经ＭＢ和Ｌ－ＮＮＡ处理后,仍可见ＥＣ３０下降３倍,最大反应比率均为１．０±０．２。后者可能与血管平滑肌产生少量ＥＤＲＦ有关。我们的结果提示ＰＥ对血管的收缩反应也受血管内皮和平滑肌产生的ＥＤＲＦ的调控     

Elevated myocardial calcium and its role in sudden cardiac death.

The contribution of intracellular calcium to ventricular fibrillation (VF) was investigated using chronically instrumented dogs with healed myocardial infarctions. A 2-minute coronary occlusion was initiated during the last minute of exercise. Fourteen animals developed ventricular fibrillation (susceptible) whereas the remaining 12 did not (resistant) during this exercise plus ischemia test. The test was then repeated for the susceptible animals after pretreatment with the intracellular calcium chelator BAPTA-AM (1.0 mg/kg). BAPTA-AM significantly reduced left ventricular dp/dt max and prevented VF in 8 of 12 susceptible animals. Conversely, myocardial cytosolic calcium levels were increased in resistant animals using the calcium channel agonist Bay K 8644 (30 micrograms/kg) or phenylephrine (10 micrograms.kg-1.min-1 3-5 min before occlusion). Bay K 8644 induced VF in all 5 resistant animals tested whereas phenylephrine induced VF in 8 of 12 resistant animals. BAPTA-AM pretreatment attenuated the hemodynamic effects of Bay K 8644 or phenylephrine and prevented VF in five of five Bay K 8644- and four of seven phenylephrine-treated animals. Finally, the endogenous level of calcium/calmodulin (Ca-CaM)-dependent phosphorylation of 170- and 55-kDa substrate proteins was measured (as an index of intracellular free calcium concentration). In the susceptible dog heart, the endogenous level of Ca-CaM-dependent phosphorylation was estimated to be two- to threefold higher than that observed in resistant dog heart. Treatment of resistant dog tissue with the calcium ionophore A23187 increased the level of Ca-CaM-dependent phosphorylation of these two proteins to the level observed in susceptible dog heart. These data suggest that elevated cytosolic calcium facilitates development of malignant arrhythmias and that elevated cytosolic calcium levels may be present in animals particularly susceptible to ventricular fibrillation.     

麻醉开胸狗左室收缩末期压力直径关系及其对正变力因素的敏感性

心室收缩末期压力容积关系和压力直径关系(ESPVR和ESPDR),是评定心室收缩能力的较好指标。本工作记录13只麻醉开胸狗左室内压,并用超声晶体植入法记录左室前后径。将阻截下腔静脉回流(IVC)降低前负荷以及狭缩胸主动脉(AO)增加后负荷两种情况下所获得的一系列连续心跳的收缩末期压力(Pes)和直径(Des),经最小二乘法求得IVC和AO时的ESPDR。结果表明:(1) IVC或AO情况下获得的Pes与Des均高度线性相关(r值分别为0.9505±0.0578和0.9298±0.0581,P均<0.001);(2) 注入多巴酚丁胺(dob)后,IVC和AO时的ESPDR直径轴截距(Do)均无改变,斜率(E_(max))则明显增大,且IVC时的增加(174.4±23.5％)大于AO时(78.7±22.6％);(3) 对照和dob两种情况下,AO时ESPDR的D_0均小于IVC时。提示麻醉开胸狗左室ESPDR的斜率对变力状态的变化敏感,但其敏感性以及ESPDR的直径轴截距受获得ESPDR所采用的改变负荷的方式的影响,其原因可能是不同方式改变负荷时引起的Pes和Ves变动范围有所不同的缘故。     

Electroacupuncture decreases the susceptibility to ventricular tachycardia in conscious rats by reducing cardiac metabolic demand

Reperfusion after a brief period of cardiac ischemia can lead to potentially lethal arrhythmias. Clinical observations and experimental work with animals suggest that acupuncture may have therapeutic effects for individuals with coronary heart disease, certain arrhythmias, and myocardial ischemia. Therefore, we tested the hypothesis that electroacupuncture reduces the susceptibility to ischemia-reperfusion-mediated ventricular tachyarrhythmias. To test this hypothesis, we measured the susceptibility to ventricular tachyarrhythmias produced by 3 min of occlusion and reperfusion of the left main coronary artery in conscious rats under two experimental conditions: 1) control and 2) with electroacupuncture. Acupuncture was simulated by electrically stimulating the median nerves, corresponding to the Jianshi-Neiguan [pericardial meridian (P) 5-6] acupoints. Results document a significantly lower incidence of ventricular tachyarrhythmias with electroacupuncture (2 of 8, 25%) relative to control (14 of 14, 100%) rats. The decreased susceptibility to tachyarrhythmias with electroacupuncture was associated with a reduced cardiac metabolic demand (lower rate-pressure product and ST-segment elevation) during ischemia.     

The protective effect of vagus nerve stimulation on catecholamine-halothane-induced ventricular fibrillation in dogs

Parasympathetic neural activity modulates some ventricular arrhythmias in man. Therefore, a canine model of arrhythmias produced by the interaction of halothane and catecholamines was used to study the effects of vagal stimulation on the induction of ventricular fibrillation. The dose of catecholamine required to induce ventricular fibrillation was determined during a constant heart rate. Vagal stimulation reversibly raised the norepinephrine dose that produced ventricular fibrillation from 16.4 +/- 2.4 to 30.0 +/- 3.8 micrograms (p less than 0.001, n = 10), and the epinephrine dose from 15.5 +/- 2.0 to 22.5 +/- 2.6 micrograms (p less than 0.001, n = 5). Following atropine, vagal stimulation failed to raise the threshold dose of norepinephrine (16.8 +/- 2.4 vs. 18.3 +/- 3.3 micrograms, nonsignificant, n = 6) or epinephrine (15.5 +/- 2.0 vs. 16.0 +/- 2.3 micrograms, nonsignificant, n = 5). Ligation of the cervical vagus nerves did not affect the epinephrine threshold dose (16.3 +/- 3.3 vs. 17.5 +/- 2.7 micrograms, nonsignificant, n = 5). Following elevation of basal vagal tone by morphine premedication, the norepinephrine threshold of 53.0 +/- 9.2 micrograms declined by a nonsignificant amount to 46.5 +/- 11.5 micrograms after vagotomy (nonsignificant, n = 5). Thus resting vagal tone does not prevent catecholamine-halothane-induced ventricular fibrillation, whereas increasing vagal tone by electrical stimulation substantially protects against this arrhythmia. The protection is mediated through a muscarinic cholinergic receptor.     

Ventricular arrhythmias after reperfusion: is there a correlation with infarct size?

The aim of this investigation was to examine whether any correlation exists between enzymatically estimated infarct size and arrhythmias arising in response to coronary reperfusion. Four hour occlusion of the left anterior coronary artery followed by reperfusion was carried out in conscious dogs. Serum creatine phosphokinase (CPK) analysis and planimetric determination of infarct size were performed. The Holter monitoring technique was used to analyze the arrhythmias. A good correlation was observed between the number of premature ventricular complexes (PVC) occurring during 4-h coronary artery occlusion and peak serum CPK values (CPKmax; r = 0.74). While PVC in the early 2-h reperfusion phase and on days 1 and 2 of the late reperfusion phase did not show a correlation with CPKmax nor with occlusion arrhythmias, arrhythmic activity on day 3 of the late reperfusion phase correlated well with CPKmax (r = 0.71) and occlusion arrhythmias (r = 0.75). Whereas it cannot be ruled out that arrhythmias on days 1 and 2 are related to coronary reperfusion as well as to the established infarction, we speculated that arrhythmias on day 3 are delayed arrhythmias in response to the occlusion procedure and not a consequence of reperfusion. Providing that arrhythmias occurring in the early reperfusion phase are almost exclusively induced by the arrhythmogenic phenomenon of reperfusion, we conclude that in contrast to occlusion arrhythmias, reperfusion arrhythmias are not markers of infarct size. Thus, a higher number of arrhythmias after reperfusion is not necessarily associated with a larger infarct size.     

牵张所致心室不应性变化的频率依赖现象及其机制

本文旨在探讨牵张所致麻醉兔心室不应性变化的频率依赖现象及其机制。采用部分夹闭兔主动脉根部以增加左室后负荷的在体心脏模型 ,观察不同起搏周长时左室后负荷增加后心室有效不应期 (effectiverefractoryperi od ,ERP)的变化及链霉素对此的影响。结果显示 ,当起搏周长为 10 0 0和 5 0 0ms时 ,左室收缩期内压增加后的心室ERP较主动脉夹闭前略有缩短 ( 10 0 0ms,3± 2ms,1 5 % ;5 0 0ms,7± 3ms,4 0 % .P >0 0 5 ) ,而起搏周长 3 0 0和 2 0 0ms时则明显缩短 ( 3 0 0ms,2 1± 5ms ,17 0 % ;2 0 0ms,19± 3ms,18 8% P <0 0 1) ;( 2 )链霉素可有效消除基本驱动周长 3 0 0和 2 0 0ms时左心室后负荷增加对ERP的影响 (P >0 0 5 ,组内比较 )。结果提示 ,牵张所致心室ERP变化具有快频率依赖性 ,且链霉素通过抑制牵张激活性离子通道的活化而消除这种电生理效应