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。     

正中神经传入冲动和刺激下丘脑背内侧核对左心室跨壁血流的影响

临床及动物实验发现,交感神经中枢过度兴奋可引起缺血样心电图改变,而刺激正中神经可改善上述变化。但上述心电图改变是否伴有心肌缺血,尚缺乏直接根据。本研究目的在于探讨电刺激下丘脑背内侧核(DMH)诱发心表面电图S-T段压低时,左心室跨壁血流(LVTBF)的变化,以及正中神经传入冲动对刺激DMH效应的影响。     

刺激大鼠下丘脑背内侧核对丘脑束旁核痛相关神经元放电的影响

本文在 79只清醒麻痹大鼠身上,用玻璃微电极记录丘脑束旁核痛兴奋(PfPE)和痛抑制(PfPI)单位的放电及其对刺激下丘脑背内侧核(DMH)的反应,并观察切割脊髓背外侧束的效应。主要结果如下:(1)刺激DMH使PfPE 单位的自发放电及痛放电有明显的抑制作用,而使PfPI 单位的自发放电增多,并解除伤害性刺激引起的抑制效应;(2)刺激DMH引起PfPE 单位的抑制效应,在切割脊髓背外侧束后仍然出现。上述结果提示:DMH 对丘脑束旁核在处理痛觉信息上具有调制作用,这种调制作用可能不通过脑干下行性抑制系统完成,而主要是通过脊髓上联系抑制丘脑束旁核神经元对痛传入的反应。     

下丘脑背内侧核在缰核兴奋诱发的心血管反应及腓深神经抑制中的作用

目的 :阐明下丘脑背内侧核 (DMH)在缰核 (Hb)兴奋诱发的心血管反应中的作用及DMH在腓深神经 (DPN)传入冲动调节Hb兴奋诱发的心血管活动中的作用及机制。方法 :脲酯和氯醛糖混合静脉麻醉的家兔 ,电刺激Hb、腓深神经 ,记录股动脉血压及心外膜电图 ,DMH内微量注射受体拮抗剂。结果 :同侧DMH微量注射谷氨酸受体阻断剂Kynurenicacid ,部分取消了电刺激Hb兴奋诱发的升压反应及缺血性心电变化反应。同侧DMH微量注射纳洛酮对腓深神经传入冲动抑制Hb兴奋诱发的上述反应有削弱作用。结论 :DMH及其中的谷氨酸受体参与电刺激缰核兴奋诱发的心血管反应 ,DMH及其中的阿片受体参与了DPN传入冲动对上述心血管反应的抑制作用     

去甲肾上腺素、甘氨酸、γ-氨基丁酸和L-谷氨酸对节段性与下行性脊髓场电位的影响

在麻醉的大鼠脊髓背部表面,记录刺激腓神经引起的节段性脊髓场电位(SP)与刺激C_2背索引起的下行性脊髓场电位(DP),观察在脊髓表面局部施加去甲肾上腺素(NE),甘氨酸(GLY),γ-氨基丁酸(GABA)和L-谷氨酸(L-GLU)时SP与DP的变化。结果表明,NE使SP与DP的N、P波波幅均明显降低,GLY、GABA、L-GLU明显降低SP与DP的N波波幅同时使SP与DP的P波明显增大。本文讨论了可能的作用机制。     

对家兔浅下颌腺分泌的初步研究

目前国内外对家免浅下颌腺的研究甚少,对其功能和分泌物的研究则未见报道。我们曾发现静脉脉注射垂体后叶素和电刺激下丘脑某些核团如下丘脑背内侧核(N.dorsomedialis hypothalami,DMH)和下丘脑前区(An(?)erior hypothalamic area,AHA)能引起此腺体分泌。在此基础上我们进行了进一步研究。     

刺激大鼠“涌泉”穴诱发的脊髓背表面电位

刺激大鼠“涌泉”穴诱发的节段性背表面电位(Y-sCDP),在远节段(L3-T7)逐渐消失,而在更远节段(C6)又记录到一个背表面电位(Y-dCDP),该电位为一慢电位正波(P波),高位横断脊髓后Y-dCDP完全消失,说明它来源于脊髓上结构,当电解损毁中脑导水管周围灰质(PAG)后,P波幅值显著降低(P<0.05),说明刺激“涌泉”穴产生的Y-dCDP为激活PAG等痛觉调制核团下行诱发的脊髓背表面电位。     

脊髓背部电刺激对延脑内侧网状结构诱发电位抑制效应的分析

实验在46只急性麻痹清醒的猫上进行。以每秒100次的重复电脉冲刺激脊髓背部(L_1)可以抑制刺激腓肠神经在延脑内侧网状结构所引起的诱发电位,抑制后效应可持续5—10分钟。在12只动物上进行了脊髓部分横断的分析,在腰2水平切断刺激部位以下的两侧侧索靠近背角部分的纤维(简称背外侧索),上述抑制作用大大减弱。如再在刺激部位上、下(胸13及腰2)分别切割背索,则抑制效应完全消失。在刺激部位以上切断两侧背外侧索并不影响抑制效应的出现。在10只动物上将背索及背外侧索从脊髓本体上分离,以观察直接刺激的效应。结果表明,分别刺激两侧背外侧索或背索对延脑诱发电位都有抑制效应,前者的作用大于后者。如同时刺激分离的背外侧索及背索则诱发电位在整个刺激期间完全被抑制,其效应与背部电刺激相似,只是所需要的电流强度较弱。上述观察证明,脊髓背部电刺激对延脑网状结构诱发电位的抑制作用是通过背外侧索的下行通路和背索的上行及下行通路而实现的。背外侧索的作用大于背索,抑制作用主要发生在脊髓水平。     

刺激下丘脑弓状核对丘脑束旁核单位痛诱发放电的影响和初步分析

1.电刺激大鼠下丘脑弓状核(ARC)对外周伤害性刺激引起的丘脑束旁核(PF)单位的痛诱发放电有明显的抑制作用,这种抑制作用可被纳洛酮所翻转。2.切断脊髓背半部后,刺激ARC对PF单位痛诱发放电的抑制作用依然存在。3.腹腔注射对氯苯丙氨酸(色氨酸羟化酶抑制剂)后,刺激ARC 的抑制作用消失。4.从ARC到PF存在着一条有内源性阿片样物质(可能是β-内啡肽)和5-羟色胺参与的上行痛觉调制通路。     

刺激中缝背核和蓝斑对下丘脑弓状核区诱发电位的影响

实验在用水合氯醛麻醉的雄性成年大鼠上完成。目的是观察刺激中缝背核和蓝斑对刺激坐骨神经诱发下丘脑弓状核区电位的影响。结果表明:(1)电刺激中缝背核和蓝斑与腹腔注射吗啡一样,可以明显抑制外周伤害性刺激所诱发的弓状核区电位的第三个迟发成分(Sw_3);(2)脑室注射及微电泳作为中缝背核和蓝斑各自所释放的主要神经递质——5-羟色胺和去甲肾上腺素也能明显地抑制 SW_3成分。     

延髓头端腹外侧区在躯体传入冲动抑制中枢性心肌缺血中的作用

电刺激麻醉家免延髓头端腹外侧区(rVLM)能诱发心外膜电图ST段明显抬高。刺激腓深神经能抑制这种反应。P5平面横断脑干、双侧电解损毁中脑中央灰质腹侧部(vPAG)或在双侧rVLM微量注射脑啡肽抗体后,均能明显减弱腓深神经的抑制作用。以上结果提示腓深神经能够抑制由rVLM诱发的心肌缺血反应。腓深神经的这种抑制效应可能有赖于中脑头端以上某些区域脑结构的完整,vPAG可能是这种抑制效应的中枢环节之一,延髓水平的脑啡肽可能参与这种抑制过程。     

正常小儿胫神经诱发脊髓电位特征和脑瘫小儿该电位的变化

采取刺激后胫神经(PTN)诱发叠加技术,利用体表无创伤性双极记录方法观察了16例正常小儿和43例脑瘫小儿的脊髓诱发电位(SCEP)。正常小儿的SCEP自下而上潜伏时逐渐延长、电压减小。从椎体C6到T10表现为Pa-Na-Pb三相波,T10～T12为Pa-Na1-Na2-Pb波,T12～L4为多相复合波。左右侧SCEP波形相似,潜伏时、电压相同,它们之间无统计学显著差别;但不同节段之间SCEP差异显著;脊髓传导速度为57.14m/s。脑瘫小儿SCEP正常者占14％;全髓反应低下者占20％;左右侧反应不对称者占46％;节段性反应低下者占15％;其它异常约占5％。不但节段间存在显著差异,而且全脊髓左右侧电压间以及颈、腰骶髓的潜伏时间出现显著差异。脊髓传导速度减低(患侧46.22m/s,对侧53.48m/s)。结果提示:(1)正常小儿脊髓活动左右对称,不同脊髓节段对PTN刺激反应不同。(2)脑瘫小儿脊髓活动左右不对称,一侧功能下降时对侧有一定代偿力,脊髓传导速度减慢。     

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients'' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal.     

电针引起脊髓P物质释放的频率依赖性

我室以往的研究表明,不同频率的电针可引起脊髓释放不同种类的阿片肽。本工作观察Ｐ物质（ＳＰ）释放的频率依赖性,电针频率选择２,４,８,１５,３０和１００Ｈｚ,分别收集电针期间及电针前后各３０ｍｉｎ的脊髓灌流液,通过放射免疫方法测定大鼠电针有效组和电针无效组Ｐ物质免疫活性（ＳＰ－ｉｒ）．结果如下：（１）电针有效组：２Ｈｚ引起ＳＰ－ｉｒ降低,与电针前相比,Ｐ＜０．０１;４Ｈｚ电针前后ＳＰ－ｉｒ比较,无统计学意义;８,１５,３０,１００Ｈｚ时ＳＰ－ｉｒ均增加（Ｐ＜０．０１）,其中１５Ｈｚ时ＳＰ增加最多（Ｐ＜０．００１）,表明刺激引起ＳＰ释放有频率依赖性。（２）电针无效组：不论应用何种频率,电针前后脊髓灌流液中ＳＰ－ｉｒ变化不大（均Ｐ＞０．０５）。提示,电针时脊髓液中ＳＰ含量变化与镇痛效果有密切关系。     

C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons

During myocardial ischemia, the cranial cervical spinal cord (C1-C2) modulates the central processing of the cardiac nociceptive signal. This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia. Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats. Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4. SCS alone induced DYN release from laminae I-V in T4, and this release was maintained during CoAO. C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO. Injection of the kappa-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO. CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment. These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart.     

Myocardial ischemia induces the release of substance P from cardiac afferent neurons in rat thoracic spinal cord

Antibody-coated microprobes were inserted into the thoracic (T3-4) spinal cord in urethane-anesthetized Sprague-Dawley rats to detect the differences in the release of immunoreactive substance P-like (irSP) substances in response to differential activation of cardiac nociceptive sensory neurons (CNAN). CNAN were stimulated either by intrapericardial infusion of an inflammatory ischemic exudate solution (IES) containing algogenic substances (i.e., 10 mM each of adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine), or by transient occlusion of the left anterior descending coronary artery (CoAO). There was widespread basal release of irSP from the thoracic spinal cord. Stimulation of the CNAN by IES did not alter the pattern of release of irSP. Conversely, CoAO augmented the release of irSP from T3-4 spinal segments from laminae I-VII. This CoAO-induced irSP release was eliminated after thoracic dorsal rhizotomy. These results indicate that heterogeneous activation of cardiac afferents, as with focal coronary artery occlusion, represents an optimum input for activation of the cardiac neuronal hierarchy and for the resultant perception of angina. Excessive stimulation of cardiac nociceptive afferent neurons elicited during regional coronary artery occlusion involves the release of SP in the thoracic spinal cord and suggests that local spinal cord release of SP may be involved in the neural signaling of angina.     

Substance P antagonist-induced spinal cord vasoconstriction: Effects of thyrotropin-releasing hormone and substance P agonists

Local spinal cord vasomotor effects of 3 substance P (SP) antagonists were studied in the rat following intrathecal (IT) administration. Each SP antagonist (3.3 nmol) increased spinal cord vascular resistance and reduced blood flow. A LH-RH antagonist analog (10 nmol) of similar molecular weight and which also contained multiple D-Trp residues did not cause spinal cord vasoconstriction. The vasoconstrictor action of the SP antagonist, [D-Arg¹, D-Pro², D-Trp^7,9, Leu¹¹]-SP ([D-Arg]-SP) was unaffected by pretreatment with a stable SP receptor agonist (5 nmol IT). Given evidence for a cerebral vasodilator action of TRH agonists, the effects of TRH (IV) and a stable TRH analog (MK-771, IT) on [D-Arg]-SP-induced vasoconstriction were also assessed. Neither TRH nor MK-771 prevented the [D-Arg]-SP-induced vasoconstriction. However, TRH (IV) but not MK-771 (IT) partially opposed [D-Arg]-SP-induced reduction in thoracic spinal cord blood flow. Thus, SP antagonists cause spinal cord vasoconstriction by a non-SP receptor mediated phenomenon. In addition, the attenuation of SP-antagonist-induced neuropathological changes previously reported with IV. TRH administration is likely due to less severe consequences of vasoconstriction in the presence of a higher initial baseline blood flow rather than direct prevention of the vasoconstriction.     

Left vagal stimulation induces dynorphin release and suppresses substance P release from the rat thoracic spinal cord during cardiac ischemia

Electrostimulatory forms of therapy can reduce angina that arises from activation of cardiac nociceptive afferent fibers during transient ischemia. This study sought to determine the effects of electrical stimulation of left thoracic vagal afferents (C(8)-T(1) level) on the release of putative nociceptive [substance P (SP)] and analgesic [dynorphin (Dyn)] peptides in the dorsal horn at the T(4) spinal level during coronary artery occlusion in urethane-anesthetized Sprague-Dawley rats. Release of Dyn and SP was measured by using antibody-coated microprobes. While Dyn and SP had a basal release, occlusion of the left anterior descending coronary artery only affected SP release, causing an increase from lamina I-VII. Left vagal stimulation increased Dyn release, inhibited basal SP release, and blunted the coronary artery occlusion-induced release of SP. Dyn release reflected activation of descending pathways in the thoracic spinal cord, because vagal afferent stimulation still increased the release of Dyn after bilateral dorsal rhizotomy of T(2)-T(5). These results indicate that electrostimulatory therapy, using vagal afferent excitation, may induce analgesia, in part, via inhibition of the release of SP in the spinal cord, possibly through a Dyn-mediated neuronal interaction.