电刺激与高渗盐水注入室旁核对血压的影响及其机制的初步探讨

本工作观察电刺激和微量高渗盐水注入室旁核(PVN)对蓝斑(LC)单位放电和血压的影响,以及阻断LC内精氨酸加压素(AVP)受体时PVN升压反应的变化,从而探讨PVN下行活动对LC单位放电的调制作用和LC在PVN调节血压过程中的地位。结果发现:(1)电刺激PVN使多数LC自发放电单位放电频率增高,并伴血压升高;(2)微量高渗盐水注入PVN也获得同样效果;(3)多数对电刺激PVN产生兴奋反应的LC单位,对高渗盐水注入PVN也表现为兴奋;(4)预先在LC注入AVP桔抗剂,可部分降低电刺激和高渗盐水注入PVN所引起的升压效应。上述结果提示:PVN调节血压的作用部分是通过PVN下行活动对LC功能影响实现的,PVN下行活动主要引起LC自发放电单位放电频率增加,并提示这一兴奋效应可能是由AVP介导的。     

电刺激大鼠扣带前回对血压和心率的影响

电刺激大鼠扣带前回(ACg),血压升高,心率加快,同时缰核(Hb)内20.7％的神经元兴奋,22.4％的神经元抑制,56.9％的神经元无反应。双侧Hb内微量注射盐酸利多卡因,可明显阻断电刺激ACg引起的心血管反应。结果表明,ACg对心血管活动的调节,一部分是通过改变Hb的活动来实现的,Hb是ACg调节心血管活动的下行性通路之一。     

刺激腓深神经对低血压或休克狗心血管活动的影响

实验在麻醉狗中进行。静脉内匀速注射硝普钠时,平均动脉压和左心室收缩压明显降低,左心室dp/dt_(max)、-dp/dt_(max)和心力环面积均明显减小。此时电刺激一侧腓深神经可使动脉血压和左心室收缩压明显升高,dp/dt_(max)和心力环面积也显著增加。停止刺激后,动脉血压和左心室收缩压逐渐回向刺激前的水平。停止注射硝普钠5～15分钟后,上述各项观察指标基本恢复到注药前的水平。在用大肠杆菌内毒素造成休克的狗中,电刺激一侧腓深神经,也能使平均动脉压和左心室收缩压升高,同时dp/dt_(max)、-dp/dt_(max)和肠系膜血管阻力明显增高,但肾血管阻力增加不明显。本实验结果与以往的实验资料一起表明,在用扩血管药造成低血压时,躯体神经刺激引起的升压效应似乎以心肌收缩力增加为主;而在内毒素休克时,躯体神经刺激可通过改善心肌收缩功能和增加内脏血管阻力而引起升压作用。     

电刺激猫小脑顶核对动脉血压和肾交感神经放电的影响

在38只麻醉及人工呼吸的猫,观察到电刺激小脑顶核嘴侧部能引起动脉血压显著升高;肾交感神经放电于刺激期间显著增加。去缓冲神经对刺激顶核所引起的血压反应的幅度和肾交感神经放电均无明显影响,但可明显延长血压反应升高相以及血压恢复期的时间。静脉注射氯庄定引起血压降低、心率减慢及肾交感神经放电的抑制,并能减弱刺激顶核引起的血压反应,但增强了刺激顶核引起的肾神经放电的变化。电解损毁延髓腹外侧面引起血压降低及肾交感神经放电的抑制,然而无论单侧还是双侧损毁延髓腹外侧面都不能阻断刺激顶核所引起的血压和肾交感神经放电的反应。以上结果表明,电刺激顶核能引起明显的心血管反应,其反应的下行性通路可能不通过延髓腹外侧面。     

电刺激兔肾脏传入神经对血压,心率及加压素释放的影响

本工作以兔为实验对象,观察电刺激肾脏传入神经（ＡＲＮ）对血压、心率、颈交感神经放电、以及加压素（ＡＶＰ）合成和释放的影响,并对ＡＲＮ进入中枢的通路作了观察。结果显示,电刺激ＡＲＮ可以引起血压下降、心率减慢、颈交感神经放电抑制等反应,ＡＲＮ的兴奋还可使下丘脑的视上核、室旁核中的ＡＶＰ含量增加,垂体中ＡＶＰ含量下降,血浆ＡＶＰ水平升高。硝普钠的降压实验和静脉注射ＡＶＰ受体阻断剂ＡＶＰａ的实验均证实了Ａ     

蓝斑核在侧脑室注射P物质引起的升压反应中的作用

本实验在体重为280～350g乌拉坦麻醉的健康大鼠上进行,观察侧脑室注射(icv.)P物质(SP)15μg的升压反应、电损毁双侧蓝斑核(LC)后对icv.SP升压反应的影响和icv.SP对LC神经元自发放电的影响及其与血压的关系。结果表明,icv.SP可使大鼠血压明显升高(P<0.001):电损毁双侧LC对大鼠正常血压无影响,但可使icv.SP的升压反应明显减弱(P<0.001):icv.SP可使大部分有反应的LC神经元放电频率增加(P<0.001),同时血压升高,二者有平行关系。上述结果提示:LC在icv.SP引起的升压反应中具有重要作用,icv.SP的升压反应可能主要通过LC下行活动而实现。     

延髓腹侧结构在刺激缰核诱发升压反应中的作用

电刺激缰核(Hb)可使大鼠血压明显升高,但心率变化不明显。电刺激Hb血压升高的同时,延髓腹侧结构(VM)中46.5％的神经元自发放电频率增加,这些神经元分布在VM的升压神经元群中,41.9％的神经元自发放电频率降低,这些神经元分布在VM的降压神经元群中,11.6%的神经元自发放电频率不变,升压和降压神经元群中均有这种神经元。单侧损毁VM的网状旁巨细胞核后,动物血压基本不变,也不影响电刺激Hb引起的升压反应。双侧损毁VM的网状旁巨细胞核后,动物血压从98.4±11.2mmHg降至45.2±10.3mmHg,阻断了电刺激Hb引起的升压反应。单侧或双恻损毁疑核及部分延髓网状核腹侧后,动物血压基本不变,且不影响电刺激Hb引起的升压反应。 上述结果表明,Hb主要通过VM中升压神经元群的网状旁巨细胞核参与心血管活动的调节。     

伏核对心血管活动的作用及其与阿片肽的关系

本文对乌拉坦麻醉大鼠采用电刺激伏核和脑内微量注射等方法,观察伏核对血压、心率的影响:(1)电刺激伏核具有明显的血压降低和心率减慢作用。(2)红藻氨酸微量注入伏核可消除上述反应。(3)伏核内注射纳洛酮可阻断电刺激伏核的心血管抑制反应(简称电刺激效应);μ受体激动剂DAGO微量注入伏核也能引起血压降低和心率减慢,减少幅度与电刺激效应相似,而κ受体激动剂U-50无此作用。(4)电刺激伏核时于蓝斑内记录到抑制性自发电活动,频率减慢,波幅交大、变宽。(5)切除颈部双侧迷走神经消除了电刺激伏核的心率变化,但降压反应依然存在。以上结果提示:伏核内某些神经元与心血管活动有关,并且至少涉及阿片肽能神经元及μ阿片受体。蓝斑和迷走神经可能参与上述心血管抑制反应。     

大鼠脊髓中的α受体在减压反射和失血性休克中的作用

大鼠脊髓蛛网膜下腔注射α激动剂可乐宁1μg,引起血压降低、心率减慢及腹腔神经节后交感神经干放电抑制。应用α阻断剂酚妥拉明阻断脊髓内源性 NE的作用,可部分抑制血压升高时反射性的心率减慢和交感神经放电抑制反应,使压力感受器反射的敏感性降低。在颈动脉放血造成不可逆性失血性休克的动物,脊髓蛛网膜下腔注射酚妥拉明可使动脉血压有一定程度的回升。以上结果表明,由脊髓α受体调制的心血管抑制效应参与减压反射以及失血性休克的发病机制。     

大鼠缰核与下丘脑外侧区在血压调节中的相互关系

电刺激乌拉坦麻醉的大鼠下丘脑外侧区(LH)可使缰核(Hb)内51.0％的单位兴奋,15.7％的单位抑制,其中发生兴奋反应的单位有15.4％可被逆行激活。双侧Hb内微量注射利多卡因,电刺激LH引起的升压反应可被阻断42.0±28.0％;反之,双侧LH内微量注射利多卡固,电刺激Hb引起的升压反应可被阻断62.0±26.4％。结果表明,LH与Hb在血压调节中相互依赖,具有协同作用。     

Spinal vasopressin modulates the reflex cardiovascular response to static contraction.

Recent evidence has demonstrated that arginine vasopressin (AVP) may modulate primary afferent activity of nociceptors in the dorsal horn of the spinal cord. Because nociceptors are group III and IV afferents, spinal AVP also may modulate the activity of group III and IV afferents that cause reflex cardiovascular responses to muscle contraction. Thus, we compared the pressor (mean arterial pressure), myocardial contractile (dP/dt), and heart rate (HR) responses to electrically induced static contraction of the cat hindlimb before and after lumbar intrathecal (IT) injection (L1-L7) of AVP (n = 9), the V1 receptor antagonist d(CH2)5Tyr(Me)AVP (n = 6), the V2 receptor antagonist d(CH2)5[D-Ile2,Ile4,Ala-NH2(9)]AVP (n = 6), and the V2 agonist [Val4,D]AVP (n = 8). After IT injection of AVP (0.1 or 1 nmol) the pressor and contractile responses to static contraction were attenuated by 55 and 44%, respectively. HR was unchanged. Forty-five to 60 min after AVP injection, the contraction-induced pressor and contractile responses were restored to control levels. V1 receptor blockade augmented contraction-induced increases in mean arterial pressure (36%) and dP/dt (49%) but not HR. V2 receptor blockade had no effect on the cardiovascular response to contraction, whereas selective V2 stimulation attenuated the dP/dt (-20%) and HR (-33%) responses but not the pressor response. These results suggest that AVP attenuates the reflex cardiovascular response to contraction by modulating sensory nerve transmission from contracting muscle primarily via a V1 receptor mechanism in the lumbar spinal cord.     

刺激下丘脑腹内侧核引起的心脏收缩性变化

本文在麻醉猫上,采用LVSP、dp/dt_(max)、V_(max)及心力环等指标,研究了刺激下丘脑腹内侧核(VMH)及其与第三脑室之间的VMH内侧邻近区(L_(0.5)引起的心脏收缩性改变。刺激VMH引起心力增强,刺激VMH内侧邻近区(L_(0.5)使心力减弱。切断两侧迷走神经后,不影响上述反应。实验结果表明:调节心脏变力性与变时性的机能结构于下丘脑某些区域中是分别存在的。     

Determination of cardiac contractility in awake unsedated mice with a fluid-filled catheter

Today, cardiac contractility in mice is exclusively measured under anesthesia or in sedated animals because the catheters available are too rigid to be used in awake mice. We therefore developed a new catheter (Pebax 03) to measure cardiac contractility in conscious mice. In this study, we evaluated the accuracy and utility of this new catheter for assessment of cardiac contractility in anesthetized and conscious mice. With the use of a balloon-pop test, the Pebax catheter with an inner diameter of 0.3 mm was found to exhibit a high natural frequency, a low damping coefficient, and a flat frequency of up to 50.5 +/- 0.6 Hz. Under anesthesia (0.5% or 1.0% halothane), no difference was found in heart rate (HR), left ventricular (LV) systolic pressure (LVSP), the maximum rates of LV pressure rise and fall (LV dP/dt(max) and LV dP/dt(min), respectively), ejection time (ET), and isovolumic relaxation time constant (tau) when measured with either the 1.4-Fr Millar or Pebax 03 catheter. However, when HR, LVSP, LV dP/dt(max), and LV dP/dt(min) were recorded with the Pebax catheter in awake mice, values were significantly higher, and ET and tau were lower, than under anesthesia, suggesting a major impact of anesthesia on these parameters. The Pebax catheter was also used in a normotensive one-renin gene mouse model of cardiac hypertrophy induced by DOCA and salt. In this model, DOCA-salt induced a severe decrease in cardiac contractility in the absence of changes in blood pressure. These data demonstrate that cardiac contractility can be measured very accurately in conscious mice. This new device can be of great help in the investigation of cardiac function in normal and genetically engineered mice.     

Divergent changes in the rate of development of pressure in the left ventricle and in the performance of the heart as a pump.

Dog hearts were prepared in situ so that heart rate (HR), left ventricular end diastolic pressure (LVEDP) and mean aortic pressure (MAP) could be controlled separately during computation of left ventricular dP/dt max and external stroke work (SW). Progressive increases in HR consistently raised dP/dt max over a wide range, and consistently lowered SW except at low rates. Progressive increases in LVEDP or MAP consistently raised both dP/dt max and SW. Infusion of noradrenaline consistently raided both dP/dt max and SW, except at very high HR when only dP/dt max was consistently raised. Our results lead us to question the validity of equating changes in pre-ejection measurements with changes in performance of the heart as a pump under abnormal conditions and in the assessment of inotropic agents.     

Compensatory recovery of vagal control of hemodynamics after unilateral vagotomy

This study investigated whether each part of the heart is evenly innervated by the left or right vagus and observed the mechanism of compensatory recovery after unilateral cervical vagotomy. HR, BP, LVSP and +/-dp/dt max all decreased one week after left vagotomy, whereas only BP and -dp/dt max decreased one week after right vagotomy. Western blot analyses revealed that the expression of M(2) receptors in the left atrium and left ventricle was upregulated after subacute (1 week) left/right vagotomy. However, significantly more cholinesterase-positive nerves in LV and RV were seen one week after unilateral vagotomy compared to the sham-operated group. In addition, baroreflex sensitivity was increased after subacute right vagotomy. The decreasing effects of ACh (0.5 microg/kg) on LVSP and +/-dp/dt max (but not on HR and BP) were facilitated by subacute unilateral vagotomy. Our present experiments indicate that 1) the working myocardium is innervated bilaterally by the vagus, 2) ventricular contractility is influenced more by denervation of the left than the right vagus and 3) up-regulation of M(2) muscarinic receptors in the left heart, increase of cholinergic nerves, and high baroreflex sensitivity could be involved in the mechanism of compensatory hemodynamic recovery via contralateral vagus overactivity, thereby amplifying contralateral vagal activity and decreasing cardiac contractility.     

安定降低家兔血压和减少刺激下丘脑诱发室性期前收缩的机制分析

家兔62只,用乌拉坦(700mg/kg)和氯醛醣(35mg/kg)静脉麻醉,三碘季铵酚制动,在人工呼吸下进行实验。用电刺激下丘脑近中线区的方法诱发室性期前收缩(HVE)。静脉注射安定(0.5mg/kg)可降低基础血压(BP),减弱刺激下丘脑引起升压反应(指收缩压峰值SBP_(max))和减少HVE。在双侧延髓腹外侧头端区(rVLM)微量注射氟安定(200μg溶于0.5μl中),γ-氨基丁酸(GABA)(6μg溶于0.5μl中)均能降低BP、SBP_(max)和减少HVE,若微量注射印防己毒素(7.5μg溶于0.5μl中)则可使BP上升并增多HVE。而于双侧延髓腹外侧尾端区(cVLM)微量注射同样剂量氟安定、GABA则无上述反应。安定降低BP、SBP_(max)和减少HVE的作用可被双侧rVLM区微量注射GABA受体拮抗剂荷包牡丹碱(3μg溶于0.5μl中)或印防己毒素所消除,但在双侧rVLM区微量注射甘氨酸受体拮抗剂士的宁(1μg溶于0.5μl中)、阿片受体拮抗剂纳洛酮(0.5μg溶于0.5μl中)、胆碱能阻断药阿托品(0.25μg溶于0.5μl中)、东莨菪碱(1.5μg溶于0.5μl中)后仍然存在。 上述结果提示,在双侧rVLM应用GABA受体拮抗剂可消除安定降低BP、SBP_(max)和减少HVE的作用,安定降低BP、SBP_(max)和减少HVE的作用可能通过GABA这一中间环节,而胆碱能受体、阿片受体、甘氨酸受体可能不起重要作用。     

头端延髓腹外侧区在侧脑室注射新斯的明所致升压中的作用

实验在47只乌拉坦(700m/kg)、氯醛糖(35mg/kg)麻醉,肌肉麻痹,人工呼吸的家兔上进行。结果观察到,侧脑室注射(icv)新斯的明引起血压升高,心率(HR)先减慢后有加快趋势,股动脉血流量(FBF)与股动脉血管通道性(COND)减小,左心室内压(LVP)增大,肾交感神经放电(RND)增加,延髓腹外侧头端(rVLM)微量注射阿托品则引起血压下降,HR减慢,FBF与COND增加,LVP与RND减小,若在icv新斯的明之前,预先向rVLM注入阿托品,可阻断新斯的明的升压效应,上述结果提示,rVLM是icv新斯的明升压效应的重要部位,rVLM区M受体功能完整是这种升压作用的关键因素。     

Assessing left ventricular systolic dysfunction after myocardial infarction: are ejection fraction and dP/dt(max) complementary or redundant?

Among the various cardiac contractility parameters, left ventricular (LV) ejection fraction (EF) and maximum dP/dt (dP/dt(max)) are the simplest and most used. However, these parameters are often reported together, and it is not clear if they are complementary or redundant. We sought to compare the discriminative value of EF and dP/dt(max) in assessing systolic dysfunction after myocardial infarction (MI) in swine. A total of 220 measurements were obtained. All measurements included LV volumes and EF analysis by left ventriculography, invasive ventricular pressure tracings, and echocardiography. Baseline measurements were performed in 132 pigs, and 88 measurements were obtained at different time points after MI creation. Receiver operator characteristic (ROC) curves to distinguish the presence or absence of an MI revealed a good predictive value for EF [area under the curve (AUC): 0.998] but not by dP/dt(max) (AUC: 0.69, P < 0.001 vs. EF). Dividing dP/dt(max) by LV end-diastolic pressure and heart rate (HR) significantly increased the AUC to 0.87 (P < 0.001 vs. dP/dt(max) and P < 0.001 vs. EF). In na?ve pigs, the coefficient of variation of dP/dt(max) was twice than that of EF (22.5% vs. 9.5%, respectively). Furthermore, in n = 19 pigs, dP/dt(max) increased after MI. However, echocardiographic strain analysis of 23 pigs with EF ranging only from 36% to 40% after MI revealed significant correlations between dP/dt(max) and strain parameters in the noninfarcted area (circumferential strain: r = 0.42, P = 0.05; radial strain: r = 0.71, P < 0.001). In conclusion, EF is a more accurate measure of systolic dysfunction than dP/dt(max) in a swine model of MI. Despite the variability of dP/dt(max) both in na?ve pigs and after MI, it may sensitively reflect the small changes of myocardial contractility.     

Frequency-dependent left ventricular performance in women and men

We aimed to determine whether sex differences in humans extend to the dynamic response of the left ventricular (LV) chamber to changes in heart rate (HR). Several observations suggest sex influences LV structure and function in health; moreover, this physiology is also affected in a sex-specific manner by aging. Eight postmenopausal women and eight similarly aged men underwent a cardiac catheterization-based study for force-interval relationships of the LV. HR was controlled by right atrial (RA) pacing, and LV +dP/dt(max) and volume were assessed by micromanometer-tipped catheter and Doppler echocardiography, respectively. Analysis of approximated LV pressure-volume relationships was performed using a time-varying model of elastance. External stroke work was also calculated. The relationship between HR and LV +dP/dt(max) was expressed as LV +dP/dt(max) = b + mHR. The slope (m) of the relationship was steeper in women compared with men (11.8 ± 4.0 vs. 6.1 ± 4.1 mmHg·s(-1)·beats(-1)·min(-1), P = 0.01). The greater increase in contractility in women was reproducibly observed after normalizing LV +dP/dt(max) to LV end-diastolic volume (LVVed) or by measuring end-systolic elastance. LVVed and stroke volume decreased more in women. Thus, despite greater increases in contractility, HR was associated with a lesser rise in cardiac output and a steeper fall in external stroke work in women. Compared with men, women exhibit greater inotropic responses to incremental RA pacing, which occurs at the same time as a steeper decline in external stroke work. In older adults, we observed sexual dimorphism in determinants of LV mechanical performance.