A comparison of the effects of pancuronium bromide and its monoquaternary analogue, ORG NC 45, on autonomic and somatic neurotransmission in the rat

1 Potentiation by pancuronium of the effects of adrenergic nerve stimulation, previously shown in cardiovascular tissues, was also found in rat anococcygeus and vas deferens, in vitro or in vivo. 2 In the pithed rat, in the presence of pancuronium, pre-junctional alpha-adrenoceptor-mediated feedback inhibition of cardiac sympathetic transmission was uncovered at relatively low stimulation frequencies by phentolamine or yohimbine. 3 The effects of pancuronium and its mono-quaternary analogue Org NC 45 on autonomic and somatic neuromuscular transmission were compared, in the pithed rat. Org NC 45 was less potent than pancuronium at blocking somatic neuromuscular transmission by a factor of 2.1, at blocking cardiac, parasympathetic transmission by a factor of 538 and at potentiating sympathetic transmission by a factor of 33.     

Effects of propranolol and tertatolol on cardiac output and regional blood flows in the rat

Tertatolol (±)-1-(tert-butylamino)-3(thiochroman-8-yloxy)-2-propanol, hydrochloride is a noncardioselective beta-adrenoceptor antagonist that is devoid of partial agonist activity. The effects of this substance on regional blood flows (RBF) in the rat were studied in comparison with those of propranolol. Rats were artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen. RBFs were assessed using radioactive microspheres of 15 ± 5 μm diameter, injected into the left ventricle. An initial injection of microspheres (⁵⁷Co) was carried out 5 min before intravenous administration of propranolol (500 μg·kg^?1), tertatolol (50 μg·kg^?1) or physiological serum. A second microsphere administration (¹¹³Tin) was performed 10 min after injection of the test substances. The animals were sacrificed 3 min after the second injection of microspheres. Neither modifications in arterial pH, pO₂, pCO₂, nor in the arterial blood pressure were observed with either propranolol or tertatolol. In contrast, a decrease in heart rate was observed (?22% with propranolol and ?14% with tertatolol). The reduction in cardiac output was 33% with propranolol and 29% with tertatolol. Propranolol reduced blood flow to the majority of structures and organs examined; such a reduction was 39% in the cerebral hemispheres, 31% in the brainstems and of greater than 20% in all the renal zones studied. With tertatolol, no significant modifications of RBF were observed in any of the cortical or medullary renal zones investigated, nor in any of the cerebral areas studied; only in several colonic areas and in the skin of the abdomen and back, were reductions in RBF observed. These results demonstrate a difference in the effects of these two substances on renal and cerebral haemodynamics.     

丹参酮、纳络酮对缺血再灌注心肌局部血流量的影响

目的：观察丹参酮、纳络酮对缺血再灌注心肌局部血流量的影响。方法：用结扎冠状动脉左前降支的方法复制犬心肌缺血再灌注模型，心肌局部血流量用氢气清除法测定。结果：丹参酮、纳络酮均能明显增加正常及部分再灌注心肌血流量，丹参酮主要增加缺血周围区血流量，纳络酮可增加缺血中心区及周围区血流量。结论：丹参酮、纳络酮均能缩小缺血区范围，纳络酮还能减轻缺血程度。     

Effect of endothelin-1 on regional kidney blood flow and renal arteriole calibre in rabbits

1. Medullary blood flow (MBF) is important in the long-term control of arterial pressure. However, it is unclear which vascular elements regulate MBF. 2. Exogenous endothelin (ET)-1 decreases cortical more than medullary blood flow. We hypothesized that ET-1 would therefore constrict afferent (AA) and efferent arterioles (EA) of juxtamedullary glomeruli less than those of cortical glomeruli. 3. Mean arterial pressure, renal blood flow and cortical (CBF) and medullary (MBF) blood flow, via laser-Doppler flowmetry, were measured before and after intrarenal ET-1 (2 ng/kg per min; n = 6) or vehicle (n = 6) in anaesthetized rabbits. Kidneys were perfusion fixed, vascular casts formed, lumen diameters measured via scanning electron microscopy and relative resistance calculated. 4. Mean arterial pressure was not significantly affected by ET-1 infusion. Cortical glomerular arteriole lumen diameters were significantly reduced in the ET-1-infused group (AA approximately 30%, EA approximately 18%; PA < 0.01), compatible with the decrease in CBF (42 +/- 3%; PGT < 0.01). Juxtamedullary arteriole lumen diameters were also significantly reduced in the ET-1-infused group (AA approximately 34%, EA approximately 21%; PA < 0.01); however, MBF did not decrease. 5. In conclusion, our data suggest that juxtamedullary arterioles are not of primary importance in the regulation of MBF because, despite reductions in juxtamedullary arteriole diameters in response to ET-1, MBF was not decreased.     

Nicorandil-induced changes in the distribution of cardiac output and coronary blood flow in pigs

Summary The present investigation was conducted to study systemic and regional haemodynamic effects of nicorandil, a potent coronary vasodilator, after intravenous or local intracoronary administration in anaesthetized or conscious pigs. Intravenous infusions of nicorandil for 10 min in both anaesthetized (15, 30, 75 and 150 g · kg^–1 · min^–1) and conscious (20, 40 and 80 g · kg^–1 · min^–1) pigs reduced arterial blood pressure, stroke volume, left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance, but increased heart rate and maxLVdP/dt. Since nicorandil decreased LVEDP at doses which did not affect arterial blood pressure, the drug may be considered as a more potent venodilator than arterial dilator. Nicorandil increased cardiac output only in conscious animals due to a more marked tachycardia (85% after 80 g · kg^–1 · min^–1) than in anaesthetized animals (30% after 75 g · kg^–1 · min^–1). The nicorandil-induced increase in heart rate and maxLVdP/dt, being substantially attenuated in conscious pigs after treatment with propranolol, can be ascribed to a reflex activation of the sympathetic nervous system following the fall in arterial pressure. Although cardiac output did not change in anaesthetized animals, intravenous infusions of nicorandil did cause a redistribution of blood flow in favour of organs such as the heart, adrenals, spleen, small intestine and brain at the expense of that to the stomach and kidneys; hepatic artery and skeletal muscle blood flow did not change. The increase in myocardial blood flow, primarily to the subepicardial layers, was associated with an enhancement in coronary venous oxygen content and was also noticed after intracoronary infusions of nicorandil (0.6, 1.5, 3 and 6 g · kg^–1 · min^–1). The above cardiovascular profile suggests a possible usefulness of nicorandil in angina pectoris as well as congestive heart failure. However, caution is needed because the strong hypotensive action and reflex-mediated tachycardia may under certain conditions aggravate myocardial ischaemia, particularly in the subendocardial layers. Send offprint requests to P. D. Verdouw     

Long-term measurement of cerebral blood flow and metabolism in a rat chronic hypoperfusion model

1. Rat bilateral common carotid artery occlusion (BCAO) was used as a chronic cerebral hypoperfusion model. We observed autoradiographically the long-term changes in regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCGU) after 2 days and 1, 4 and 8 weeks of BCAO and in controls. Regions evaluated included the cerebral cortex, white matter and basal ganglia. Pathological changes were also observed with Klüver-Barrera and haematoxylin-eosin staining. 2. After 2 days, rCBF was significantly reduced to 33-58% in the cortex, white matter and amygdala and similar reductions were observed after 1 week. 3. After 4 weeks, rCBF recovered; however, rCBF remained significantly reduced in the occipital cortex, white matter, globus pallidus and substantia nigra. 4. After 2 days, rCGU was mostly maintained but, after 1 week, rCGU was reduced significantly to 40-70% in the cortex, white matter, basal ganglia and thalamus. Four weeks later, these reductions were no longer seen. 5. Rarefaction of the white matter was observed from 1 week. 6. These results showed that the BCAO in rats is an appropriate model for chronic cerebral hypoperfusion and that uncoupling of rCBF and rCGU was observed from 2 days until 4 weeks in the white matter.     

Effect of indoramin on finger blood flow in vasospastic patients

Summary The effect of indoramin on blood pressure, heart rate and finger blood flow was investigated in eleven patients with essential acrocyanosis. Indoramin 50 mg t. i. d. and placebo were administered for 6 weeks, in random order in a double blind, cross-over trial. In 8 of the 11 patients, finger blood flow, measured by venous occlusion plethysmography was higher and resistance was lower with indoramin. There was no significant change in blood pressure or heart rate. Thus, indoramin may be useful when a decrease in alpha-adrenoreceptor tone in the fingers is desirable.     

养血清脑颗粒对慢性脑缺血大鼠脑血流量及认知功能的影响

目的：观察养血清脑颗粒(YQG)对慢性脑缺血大鼠脑血流量及认知功能的影响。方法：Wistar大鼠双侧颈总动脉永久结扎造成慢性脑缺血模型,激光多普勒血流仪检测额叶皮质局部脑血流量；Morris水迷宫检测认知功能。结果：术后模型组大鼠脑血流量骤降,并呈慢性持续下降趋势(P＜0．05)；大鼠出现认知功能障碍,隐匿平台逃避潜伏期和游泳距离明显延长(P＜0．05,P＜0．01),空间探索实验逃避潜伏期明显延长,穿越次数明显减少(P＜0．01),平台象限游泳时间和距离均缩短(P＜0．01)。YQG 3个剂量组均能明显增加脑血流量,改善认知障碍(P＜0．05或P＜0．01)。结论：YQG能明显改善慢性脑缺血大鼠局部脑血流量,提高学习记忆能力,有随疗程的增加而作用增强的趋势。     

The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog

1. In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an alpha-glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown. 2. In open-chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50-100 microg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres. 3. There was no significant difference in regional myocardial blood flow in the risk and non-risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol-treated group compared with the control group (1.3 +/- 0.4 vs 2.2 +/- 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area. 4. In conclusion, in the present study miglitol improved ST segment depression and attenuated the accumulation of myocardial interstitial lactate during anginal ischaemia without altering regional myocardial blood flow. Miglitol has an anti-anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow.     

注射用辛芍对大鼠脑缺血再灌注损伤的保护作用和对脑微循环血流量的影响

目的:观察注射用辛芍对大鼠中动脉阻断(MCAO)局灶性脑缺血再灌注损伤及脑缺血局部微循环血流量的影响。方法:采用栓线法建立局灶性脑缺血再灌注模型,观察注射用辛芍(0.31,0.62,1.25g.kg-1)分别对MCAO再灌注大鼠神经行为学、脑梗死率和脑组织超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)活性,丙二醛(MDA)含量及脑组织病理变化的影响;使用相同动物模型,以激光多普勒血流仪监测各药物干预组对大鼠脑微循环血流的影响。结果:注射用辛芍可明显降低或改善MCAO大鼠行为障碍、脑梗死率及缺血所致组织病理改变,提高SOD活力,降低NOS活性及MDA含量,改善缺血大鼠脑微循环。结论:注射用辛芍对实验性脑缺血具有显著的保护作用,其作用机制可能与增强病灶组织抗氧化和改善局部脑微循环血流有关。     

赛庚啶对心、脑、肾血流量的影响及对实验性脑血栓的影响

目的观察赛庚啶对大鼠脑血流量、心肌血流量及肾血流量的影响及其对以ADP、凝血酶、肾上腺素复合物为诱导剂的实验性脑血栓的影响。方法：放射性微球法。结果：赛庚啶iv2mg·kg(－1)可以使正常SD大鼠脑血流量增加28．6％，心肌血流量增加43．0％，肾皮质血流量增加45．6％，与对照组相比差异有显著性。ivlmg·kg(－1)可以抑制实验性脑血栓的形成。结论：赛庚啶可以改善心、脑、肾的血液循环。     

Differential effects of anesthetic agents on regional blood flow and central hemodynamic parameters in rats

Three commonly used anesthetic agents (pentobarbital, chloralose-urethane, and inactin) were studied in a rat model. The radiolabeled microsphere technique was used to evaluate rats anesthetized (no reaction to pain stimulus) with the three drugs as compared to awake unanesthetized animals. Of the three anesthetic agents studied, pentobarbital caused the smallest alteration in central hemodynamic parameters. Chloralose-urethane significantly lowered cardiac output (56%), stroke volume (35%), and minute work (51%). Chloralose-urethane also significantly increased total peripheral resistance (59%). Inactin at the concentration used in the present study had very little effect on cardiac index, heart rate, stroke volume, and minute work but significantly increased total peripheral resistance and mean arterial pressure. All three anesthetic agents reduced cerebral and skeletal muscle blood flows equally. While pentobarbital and chloralose-urethane significantly decreased renal blood flow (33%), inactin did not change flow to the kidney. It is concluded that anesthetic agents used in small animal experiments should be chosen carefully so that they do not influence blood flow to the organ being studied.     

龙甲血脉通胶囊的抗心脏房室传导阻滞及活血化淤作用

目的探讨龙甲血脉通胶囊(LO)抗心脏房室传导阻滞及活血化淤作用。方法采用盐酸维拉帕米诱导的家兔房室传导阻滞模型以及腺苷诱导豚鼠房室传导阻滞模型,考察LO抗心脏房室传导阻滞作用;采用ADP诱导的家兔血小板聚集试验和质量分数为10%的高分子右旋糖酐诱导大鼠血液流变学影响实验,考察LO的活血化淤作用。结果LO(0.80、0.40 g.kg-1)能够显著或者非常显著缩短盐酸维拉帕米诱导的家兔心电图PR间期、PP间期以及恢复正常心电图时间的延长(P<0.05,P<0.01),同时能显著缩短腺苷诱导豚鼠心电图PR间期的延长(P<0.05,P<0.01);能够降低ADP诱导的血小板聚集率(P<0.05,P<0.01),能够降低质量分数10%的高分子右旋糖酐诱导的大鼠高、中、低切血液黏度(P<0.05,P<0.01)。结论LO具有抗心脏房室传导阻滞和活血化淤作用。     

3,4,5-三甲氧基苯甲酸-8-(二乙胺基)-辛酯对大鼠脑血流及其自动调节功能的影响

用激光多谱勒血流仪连续测量脑血流量（CBF），观察3,4,5-三甲氧基苯甲酸-8-(二乙胺基)-辛酯(TMB-8)对麻醉大鼠CBF及脑血流自动调节功能的影响. 结果表明, TMB-8 0.5, 1.0和2.0 mg·kg^-1呈剂量依赖性地增加CBF 5%, 20% 和34%. 其中仅2.0 mg·kg^-1组使平均动脉压（MABP）降低6%. 而尼莫地平(Nim)0.01 mg·kg^-1在使CBF增加21%的同时，使MABP降低了27%. 麻醉大鼠脑血流自动调节的MABP低限是5.3 kPa. 在MABP 4.0 kPa时TMB- 8 2.0 mg·kg^-1能增加脑血流自动调节能力，而Nim 0.01 mg·kg^-1则无明显作用. 提示TMB-8增加CBF和增强脑血流自动调节能力是其抗脑缺血作用的机理之一.     

川芎嗪对急性胰腺炎大鼠胰腺血流量影响与治疗作用

应用牛磺胆酸钠诱发大鼠急性胰腺炎(AP)模型.观察了川芎嗪(TMP)对AP大鼠胰腺血流量和存活率的影响.发现TMP显著增加胰腺相对血流量及灌注量.减轻胰腺病理形态损伤.提高大鼠存活率。通过测定血浆TXB_2、6-酮PGF_la及血小板聚集率.显示TMP能纠正AP时TXA_2-PGI_2失衡.降低血小板聚集率。提示TMP的治疗作用可能系通过调节TXA_2-PGI_2平衡而改善AP时胰腺血液循环紊乱而实现。     

全剂量替罗非班联合PCI术对急性心肌梗死患者心功能及TIMI血流分级的影响

目的研究全剂量替罗非班联合经皮冠状动脉介入治疗(PCI术)应用于急性心肌梗死的效果。方法选取2016年10月~2019年10月的急性心肌梗死患者96例,均行PCI术,其中48例采用全剂量替罗非班治疗为全剂量组,48例采用半剂量替罗非班治疗为半剂量组。比较两组治疗前、治疗24 h后心功能[左室射血分数(LVEF)、左室舒张末期内径(LVEDD)]、心肌梗死溶栓治疗(TIMI)血流分级及心血管不良事件发生率。结果治疗24 h后全剂量组LVEF大于半剂量组,LVEDD小于半剂量组(P <0.05);全剂量组TIMI血流分级优于半剂量组(P <0.05);全剂量组不良心血管事件发生率为8.33%,半剂量组不良心血管事件发生率为20.83%,组间比较差异无统计学意义(P> 0.05)。结论全剂量替罗非班联合PCI术治疗急性心肌梗死能提高心功能,改善TIMI血流分级,安全性高。     

Effects of nicotine,carbon monoxide and tobacco smoke on regional blood flow in the cerebral cortex

Small samples of cigarette smoke introduced into the lungs of the anaesthetized cat caused an increase in cerebral blood flow. Two constituents of tobacco smoke — nicotine and carbon monoxide — were shown to contribute to the response.     

Effects of verapamil on regional myocardial blood flow and ST segment. Role of the induced bradycardia

The effects of verapamil on regional myocardial blood flow and on the $\text{ST}$ segment were studied in both normal and ischemic regions in dogs with and without cardiac pacing.In the absence of cardiac pacing, verapamil (0.05 mg/kg/min/10 min) induced marked bradycardia, a drop in blood pressure and an increase in epicardial and endocardial flows both in normal and ischemic regions of the heart. However, in ischemic regions, redistribution was favorable since the endo/epi ratio increased from 0.46 to 0.61 (p<0.01) whereas this ratio did not vary in normal regions (0.94 vs. 0.92). This increase is accompanied by less marked $\text{ST}$ segment elevation during coronary occlusion in dogs treated with verapamil.In dogs with cardiac pacing, administration of verapamil under the same conditions again induced a drop in blood pressure and, in normal regions only, a homogeneous but less marked increase in epicardial and endocardial flows, the endo/epi ratio varying from 0.94 to 0.98. In contrast, in ischemic regions, blood flow was not modified by verapamil, but the endo/epi ratio dropped from 0.46 to 0.31 (p<0.01), while the $\text{ST}$ segment elevation observed did not differ from that recorded during the control occlusion.These results demonstrate the major role of verapamil-induced bradycardia in the anti-anginal effects of this drug.     

玉郎伞提取物对心脏血流动力学和冠脉流量的影响

目的：研究玉郎伞提取物(YLS)对冠脉流量(CF)和心脏血流动力学的影响。方法：以比Langcndorff法制备大鼠离体心脏，观察心肌收缩幅度并测定CF。采用心室内插管技术，连接MS2000多媒体生物信号记录系统测定静注YLS前及药后的左心室收缩压(LVSP)、左心室终末舒张压(LVEDP)、心率(HR)、左室压最大上升速率(dp/dtmax)、左室压最大下降速率(-dp/dtmax)、左室开始收缩至dt／dtmax的间隔时间(t-dp/dmax)等血流动力学指标的影响。结果：YLS显著增加冠脉流量(P＜0.05)，明显降低LVSP和dp／dtmax，延长t-dp/dmax，减慢HR及降低心肌的收缩振幅(P＜0.01或P＜0.05)，对LVEDP和-dp/dtmax等舒张性指标无明显影响。结论：YLS具有抑制心肌收缩力、减慢心率和增加冠脉流量作用。