甲磺酸法舒地尔对犬脑血管痉挛的扩张作用

目的：观察法舒地尔的酸根改构体甲磺酸法舒地尔对犬脑血管痉挛的舒张作用以及对脑血流量的调节。方法：采用犬十二指肠插管给予麦角胺咖啡目制作大脑血管痉挛模型，用电磁流量计测定颈内动脉血流量，椎动脉血流量。结果：（1）甲磺酸法舒地尔0．35，1．2，3．5mg·kg^-1给药后可依剂量地降低脑血管阻力，增加脑血流量，作用持续2h以上；最大流量增加值与模型对照组比较可达27％；（2）甲磺酸法舒地尔3．5mg·kg^-1给药后可使股动脉血管阻力降低，股动脉血流量升高；最大流量增加值与模型组对照比较可达16％。结论：甲磺酸法舒地尔对犬痉挛脑血管有扩张作用，可明显降低脑血管阻力，增加脑血流量。     

南苜蓿总皂苷对麻醉犬脑血流动力学的影响

目的:观察南苜蓿总皂苷对麻醉犬脑血流量、脑血管阻力的影响。方法:将36只麻醉犬随机分为6组,分别为南苜蓿总皂苷高、中、低剂量组、尼莫地平组、脑心通组、对照组,麻醉后股动脉插管,经压力换能器连接多导生理记录仪,颈总动脉连接电磁血流量计,按相应分组经十二指肠给药,测定给药前后的颈总动脉血流量、收缩压、舒张压、平均动脉压、心率、呼吸次数等变化率,计算脑血流量和脑血管阻力。结果:南苜蓿总皂苷高剂量(0.42 g·kg^-1)能显著增加麻醉犬给药后40,50,70 min的脑血流量变化率并降低给药后40,50,70 min脑血管阻力变化率,同时降低给药后40,70 min的收缩压和舒张压变化率(P<0.05或P<0.01),对心率和呼吸次数无影响。结论:南苜蓿总皂苷通过增加脑血流量,降低脑血管阻力,降低血压,从而改善脑血流动力学指标,防治缺血性脑血管病。     

香青兰有效部位滴丸对Beagle犬血流动力学的影响

目的:观察香青兰有效部位滴丸(简称香青兰滴丸)对Beagle犬血流动力学的影响。方法:采用麻醉开胸犬在体心脏,分别测定十二指肠给予香青兰滴丸25,50,100 mg.kg-1后血压、心率、左心室和心脏泵血功能、总外周阻力、冠脉流量及冠脉阻力的变化。结果:香青兰滴丸50,100 mg.kg-1降低冠脉阻力(CR),总外周阻力(TPR)和左室舒张末期压(LVEDP),减少左室做功(LVW),明显降低收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP),增加每百克心肌的血流量(CF)。结论:香青兰滴丸对Beagle犬心脏功能有一定的调节和改善作用。     

血栓通注射液对犬脑循环的影响研究

目的：观察血栓通注射液（XST）对麻醉犬脑循环的影响。方法：杂种犬24条,随机分为对照组、血栓通注射液低、中、高剂量组,单次左侧股静脉滴注给药（匀速滴注15min）观察收缩压（SAP）、舒张压（DAP）、平均动脉血压（MAP）、心率（HR）、脑血流量（CBF）、脑血管阻力（CVR）和颈内动脉流量等指标的变化。结果：血栓通注射液10、20mg·kg^-1在静脉滴注给药后10—30min均能明显增加脑血流量和颈内动脉流量,降低脑血管阻力（P〈0．05）。各剂量组对血压、心率影响均不明显（P〉0．05）。结论：血栓通注射液能明显增加脑血流量和颈内动脉流量,降低脑血管阻力,具有改善麻醉犬脑循环的作用。     

桂利嗪与尼莫地平对离体血管的舒张作用

目的:比较桂利嗪与尼莫地平对于离体血管的舒张作用.方法:分离SD大鼠胸主动脉,在内皮完整及去内皮的血管环上分别加入桂利嗪及尼莫地平,以累积剂量法给药至最大舒张剂量,观察药物对两种离体血管的舒张作用.结果:尼莫地平与桂利嗪均能剂量依赖性舒张内皮完整及去内皮血管.尼莫地平对内皮完整血管的舒张作用强于去内皮血管的舒张作用.桂利嗪对去内皮血管的舒张作用与内皮完整血管的作用相似.结论:尼莫地平的扩血管作用部分为内皮依赖性的,部分为对平滑肌的直接扩张作用;桂利嗪的扩血管作用主要是通过对平滑肌的直接扩张作用实现的.     

鸟苷对大鼠胸主动脉血管环的舒张作用及机制

目的研究鸟苷对大鼠离体血管环的影响,并探讨其可能的作用机制。方法分离SD大鼠胸主血管环,分成去内皮组和内皮完整组,采用离体血管环实验方法,经生物信号采集与分析系统测定血管环张力的变化,观察鸟苷的舒血管作用并探讨不同抑制剂对鸟苷舒张大鼠离体血管环作用的影响。结果鸟苷(10-9～10-5 mol.L-1)对基础状态下或KCl预收缩血管环的张力无影响;对PE预收缩的血管环有内皮依赖性舒张作用;环氧合酶抑制剂吲哚美辛孵育对鸟苷的舒张作用无明显影响;一氧化氮合酶抑制剂L-NAME或鸟苷酸环化酶抑制剂亚甲蓝可阻断鸟苷的血管舒张作用。结论鸟苷对大鼠离体胸主动脉有浓度依赖性舒张作用,其舒张作用可能与NO-GC-cGMP途径相关。     

三七总苷促进兔髂动脉内皮剥脱术后血管内皮细胞的修复作用

目的:探讨三七总苷促进兔髂动脉球囊内皮剥脱术后血管内皮细胞的修复作用。方法:将新西兰兔随机分为10,30,50mg.kg-13个三七总苷治疗组、生理盐水阴性对照组和阿司匹林(4.67mg.kg-1)阳性对照组,分别于髂动脉球囊剥脱术前2d开始每天按相应剂量经耳缘静脉注射药物一次至术后4周。处死动物后取出髂动脉。随后分别观察离体髂动脉环对苯肾上腺素(PE)收缩血管后乙酰胆碱(Ach)的舒张反应,并用扫描电镜观察血管内皮细胞形态变化。结果:髂动脉球囊剥脱术造成血管内皮形态和功能严重损伤,三七总苷30和50mg.kg-1组内皮细胞形态和内皮依赖性舒张功能都可见显著恢复,50mg.kg-1组血管环对Ach的舒张反应接近正常水平,而三七总苷10mg.kg-1对内皮细胞形态及血管环对Ach舒张效应的恢复作用较弱,其作用强度与阿司匹林组相近。结论:三七总苷可促进髂动脉球囊内皮剥脱术后内皮细胞形态和功能的修复。     

栀蛭注射液对犬心脑血管作用的影响

目的了解栀蛭注射液在动物体内对心脑血管的药理学作用基础。方法采用电磁流量计直接测定犬脑血管流量,并测定犬Ⅰ、Ⅱ血流动力学参数。结果给犬静脉注射栀蛭注射液,对犬颈内动脉血管有一定的扩张作用,能增加每百克脑组织血流量,降低脑血管阻力;能增加犬冠状动脉和主动脉的血流量、增加每分钟百克心肌血流量、增加心搏出量、降低总外周血管阻力和冠脉阻力作用。结论栀蛭注射液有直接扩张心脑血管的作用。     

三七通舒胶囊治疗脑血管痉挛的疗效观察

脑血管痉挛是由于多种因素引起脑局部血管收缩及脑血流量减少,导致脑供血不足.脑血管痉挛的脑血流表现以大脑中动脉、大脑前动脉痉挛为主、大脑后动脉次之、椎动脉及基底动脉痉挛少见,以平均血流速度(Vm)明显增高,阻力指数、脉动指数(PI)稍高于正常为特点.而无其他参数及频谱图像的改变,痉挛表现为单支或多支血管的痉挛,以双侧血管痉挛为主.     

荞麦花叶总黄酮的舒张血管作用及其机制

目的探讨荞麦花叶总黄酮(TFBFL)对大鼠离体胸主动脉的舒张作用与机制。方法采用离体血管环灌流装置,经生物信号采集与分析系统测定血管环张力的变化;激光扫描共聚焦显微镜技术检测血管平滑肌细胞内钙浓度。结果在苯肾上腺素(phenylephrine,PE)10-6mmol.L-1或KCl60 mmol.L-1预收缩的保留内皮和去除内皮的血管环中,TFBFL均能够浓度依赖性的引起血管舒张;相对于去除内皮的血管环,TFBFL对保留内皮的血管环的舒张作用更明显。保留内皮的血管环用一氧化氮合酶抑制剂L-NAME(100mmol.L-1)预孵后,TFBFL诱导的血管舒张作用明显减弱。在无钙灌流液中,用KCl 60 mmol.L-1去极化去除内皮的血管环后,逐渐加入Ca2+,使血管环呈浓度依赖性收缩;TFBFL(0.8 mg.L-1)孵育10 min后可使CaCl2的量效曲线向下移位且可使PE在无钙灌流液中诱导的血管环最大收缩幅度明显降低。激光扫描共聚焦显微镜检测细胞内钙的结果表明,TFBFL浓度依赖性(0.4、0.8 mg.L-1)的抑制了静息状态平滑肌细胞质内钙浓度的升高。结论 TFBFL能够浓度依赖性舒张大鼠胸主动脉,其作用机制可能是降低细胞内游离Ca2+浓度;对于保留内皮的血管环,TFBFL也作用于血管内皮细胞,促进一氧化氮的释放,引起血管舒张。     

豨莶草胶囊对麻醉犬脑血流量及脑血管阻力影响的研究

目的:研究豨莶草胶囊对麻醉犬脑血流量(CBF)、脑血管阻力(CVR)、血压、心电图及心率的影响。方法:将犬结扎一侧颈外动脉及椎动脉,以电磁流量计测颈动脉血流量,以多道生理记录仪记录血压、心电图及心率的变化。结果:豨莶草胶囊可显著增加麻醉犬的CBF,降低CVR,但对麻醉犬的血压、心电图及心率无显著影响。结论:豨莶草胶囊可通过增加CBF及降低CVR,改善脑血液循环。     

注射用尼莫地平脂质体对麻醉犬脑循环的影响

目的:研究注射用尼莫地平脂质体对麻醉犬脑循环的影响。方法:36只犬随机分为6组,分别为对照组、溶媒组、尼莫地平脂质体0.3、0.15、0.075mg·kg~(-1)组和尼莫地平0.15mg·kg~(-1)组,静脉滴注给药,观察不同时间点脑血流量(CBF)、脑血管阻力(CVR)、平均动脉压(MAP)、心率(HR)和心电图(ECG)的变化。结果:尼莫地平脂质体各剂量组均可明显增加麻醉犬CBF,降低CVR(P<0.01);0.3、0.15mg·kg~(-1)可引起麻醉犬MAP和HR下降,QT间期延长(P<0.05);等剂量(0.15mg·kg~(-1))的尼莫地平脂质体与尼莫地平相比,增加CBF作用相当,降低CVR的作用更强(P<0.01)。结论:尼莫地平脂质体能增加CBF,降低CVR和MAP;剂量大时有减慢HR、延长QT间期的作用。     

Effect of the newly synthetized calcium antagonist isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5- dicarboxylate on cerebral venous outflow in dogs

The effects of intravenous administration of isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydroyridi ne- 3,5-dicarboxylate (NB-818) on mean arterial blood pressure (MBP), heart rate (HR), cerebral blood flow (CBF), cerebral vascular resistance (CVR), arteriovenous oxygen difference (AVO2D), cerebral metabolic rate of oxygen (CMRO2) and blood gases were studied using the method of the cerebral venous outflow in dogs, and compared to those of nicardipine and nimodipine. 1. NB-818, nicardipine and nimodipine (1-10 micrograms/kg) decreased MBP dose-dependently accompanied by a decrease in HR only at doses of 10 micrograms/kg (NB-818) and 3-10 micrograms/kg (nimodipine). 2. NB-818 (1-10 micrograms/kg) increased CBF dose-dependently accompanied by a decrease in CVR. When comparing the potency or duration of action, the action of NB-818 showed a slower onset and was longer-lasting than that of nicardipine or nimodipine. 3. All three drugs (1-10 micrograms/kg) did not significantly affect CMRO2, AVO2D and blood gases (pH, pCO2 and pO2). These results indicate that the increase in CBF with NB-818 is longer in duration than that with nicardipine or nimodipine, and its effect is due to the dilatation of cerebral vessels. In addition, these results suggest that NB-818 is a potent cerebrovasodilator.     

Effects of sumatriptan on the cerebral intraparenchymal microcirculation in the cat.

1. Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective against the headache of migraine. The effects of sumatriptan injected via the carotid artery on the cerebral microcirculation were studied in 10 anaesthetized cats. 2. The local cerebral blood volume (CBV), mean transit time of blood (MTT) and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. 3. Sumatriptan at 5 and 50 micrograms kg-1 had no significant effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500 micrograms kg-1 of sumatriptan reduced the CBV, prolonged the MTT, and decreased the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg-1, elicited transient reductions in CBV and CBF, which were attributable to the rapid and marked falls of MABP seen with this dose. 4. Thus, while a high dose of sumatriptan (500 micrograms kg-1) exhibits direct vasoconstrictor actions on the cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit no vasoconstriction. The data do not support a vasoconstrictor action of sumatriptan playing a primary role in reversing the headache of migraine.     

牡荆素对麻醉犬血流动力学及心肌耗氧量的影响

目的研究牡荆素对麻醉犬血流动力学及心肌耗氧量的影响。方法杂种犬30只,人工呼吸下开胸,给药后观察其心率（HR）、血压（MAP）、心输出量（CO）、冠脉血流量（CBF）、左室压（LVP）及血氧含量。计算冠脉阻力（CVR）和体循环总外周阻力（TPR）等血流动力学指标。采用多普勒超声血流仪测定麻醉犬冠脉流量和心输出量,用血气分析仪测定血氧含量。结果牡荆素可减慢心率和左心室内压,并显著增加麻醉犬冠脉血流量和心输出量,降低总外周血管阻力和冠脉阻力,提高心搏出量、心搏指数及心脏指数。结论牡荆素可显著改善麻醉犬血流动力学参数。     

Cardiovascular activity of rasagiline, a selective and potent inhibitor of mitochondrial monoamine oxidase B: comparison with selegiline

Selegiline is used for treating Parkinson's disease. Despite its efficacy, the clinical use of selegiline in combination with l-dihydroxphenylalanine in Parkinsonian patients is hampered by cardiovascular complications, such as hypotension. This study was designed to compare in rats the cardiovascular effects of selegiline and rasagiline, their metabolites l-methamphetamine and aminoindan (TVP-136), respectively, and the second rasagiline metabolite non-monoamine oxidase (MAO) inhibitor TVP-1022 (N-propargyl-1S(-)aminoindan). Intravenous (i.v.) administration of selegiline and rasagiline (1 mg kg(-1)) to anaesthetized rats (thiobutabarbital, 100 mg kg(-1), i.p.) did not affect mean arterial pressure (MAP), carotid blood flow (CBF) or carotid vascular resistance (CVR). Selegiline (10 mg kg(-1), i.v.) decreased MAP, CBF and increased CVR. In contrast, rasagiline (10 mg kg(-1), i.v.) caused a small transient decrease in MAP, while CBF and CVR were unchanged. l-methamphetamine (1 mg kg(-1), i.v.) administration provoked a dramatic and long-lasting depressor response, decreased CBF and increased CVR. In contrast, injection of aminoindan or TVP-1022 at a similar dose produced gradual nonsignificant decreases in MAP and CBF. Chronic oral treatment (21 days) of awake rats with selegiline at 10 mg kg(-1) decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP, whereas heart rate was unaffected. Since the effective MAO-B inhibitory and clinical dose of rasagiline is about one-tenth that of selegiline, administration of 1 mg kg(-1) day(-1) rasagiline resulted in moderate decreases in SBP, DBP, and MAP, which were significantly lower than those caused by the 10 mg kg(-1) day(-1) dose of selegiline. These findings indicate that rasagiline, when given at doses equivalent to selegiline, is less likely to be hypotensive.     

Acute haemodynamic effects of felodipine, verapamil and hydralazine in the anaesthetized dog

Felodipine, a potent dihydropyridine calcium antagonist with a pronounced vascular selectivity, was given intravenously (0.006-0.025 mumol kg-1) to anaesthetized, open-chest dogs with denervated hearts. The result was a dose-dependent decrease in mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and left ventricular end-diastolic pressure remained relatively unchanged. Cardiac tension work (TTI) and oxygen consumption (MVO2) were reduced, probably due to the decrease in afterload. The relative reduction of the coronary vascular resistance (CVR) was greater than that of TPR. The hypotensive effect of verapamil (0.05-0.20 mumol kg-1) was small and MAP decreased mainly via a decrease in HR and SV. Higher doses of verapamil which induced vasodilatation could not be given without the development of complete atrio-ventricular dissociation. Hydralazine (11-45 mumol kg-1) decreased TPR and CVR in parallel but the decrease in MAP was partly counteracted by a powerful increase in HR, SV and cardiac inotropy which was associated with elevated catecholamine levels in plasma. When MAP and HR were maintained constant by means of aortic balloon inflation and atrial pacing, felodipine markedly increased coronary blood flow and coronary sinus oxygen saturation while SV, TTI, inotropy and MVO2 remained relatively unchanged. It is concluded that felodipine markedly dilates peripheral resistance vessels, and in particular those in the coronary vascular bed, without any cardiodepressant effects.