Kinetics of Regional Blood-Brain Barrier Glucose Transport and Cerebral Blood Flow Determined with the Carotid Injection Technique in Conscious Rats

Anesthetics, particularly barbiturates, have depressive effects on cerebral blood flow and metabolism and likely have similar effects on blood-brain barrier (BBB) transport. In previous studies utilizing the carotid injection technique, it was necessary to anesthetize the animals prior to performing the experiment. The carotid injection technique was modified by catheter implantation in the external carotid artery at the bifurcation of the common carotid artery. The technique was used to determine cerebral blood flow, the Km, Vmax, and KD of glucose transport in hippocampus, caudate, cortex, and thalamus-hypothalamus in conscious rats. Blood flow increased two to three times from that seen in the anesthetized rat. The Km in the four regions ranged between 6.5 and 9.2 mM, the Vmax ranged between 1.15 and 2.07 mumol/min/g, and the KD ranged between 0.015 and 0.035 ml/min/g. The Km and KD in the conscious rat did not differ from the values seen in the barbiturate anesthetized rat. The Vmax, on the other hand, increased two- to three-fold from that seen in the anesthetized rat and was nearly proportional to the increase in blood flow seen in the conscious rat. The development of the external carotid catheter technique now allows for determination of BBB substrate transport in conscious animals.     

Age-related changes of elements in thoracic and abdominal aortas and coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries and relationships in elements among their arteries

To elucidate whether the accumulation of elements occurred simultaneously in the various arteries with aging, the authors investigated age-related changes of elements in the eight arteries, such as the thoracic and abdominal aortas and the coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries, and the relationships in the element contents among their arteries. After ordinary dissection by medical students was finished, the thoracic and abdominal aortas and the coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries were resected from the subjects, who ranged in age from 58 to 94 yr. The element contents were analyzed by inductively coupled plasma-atomic emission spectrometry. It was found that the accumulation of Ca was the highest in the common iliac artery and decreased in the order of the uterine artery, abdominal aorta, coronary artery, thoracic aorta, splenic artery, common carotid artery, and pulmonary artery. Regarding the relationships in the element contents among the eight arteries, it was found that there were significant direct correlations in the contents of Ca, P, Mg, Zn, Fe, and Na between the coronary and splenic arteries, and there were significant correlations in the contents of Ca, P, and Mg between the abdominal aorta and pulmonary artery.     

缺血性眩晕大鼠模型的建立

目的建立缺血性眩晕大鼠模型,为研究相关治疗药物奠定基础。方法采用手术结扎右侧颈总动脉（common carotid artery,CCA）和右侧锁骨下动脉（subclavian artery,SCA）致大鼠右侧半脑不完全脑缺血建立缺血性眩晕大鼠模型。记录逃避电刺激所需的时间（潜伏期）作为衡量眩晕严重程度的指标,测量造模前后右侧前庭神经核组织血流量,计算血流量变化率,评价脑供血状况。结果 1.与假手术组相比,模型组大鼠潜伏期明显延长（P〈0.01）,造模成功;与模型组比较,盐酸地芬尼多和天保宁能够明显缩短大鼠潜伏期（分别缩短61.9%、52.0%,P〈0.01）。2.结扎右侧CCA及SCA后,与对照组相比,模型组大鼠前庭神经核组织血流量明显减少（P〈0.01）,造模成功;与模型组相比,天保宁能明显增加结扎动脉后组织血流量,在结扎后5、10、15、20、25、30 min血流量分别增加92.8%、83.8%、77.3%、77.9%、65.7%、55.8%（P〈0.01）。结论该模型持久稳定,动物脑部缺血明显,并且能够很好地反映动物眩晕时间及眩晕程度,可有效应用于抗缺血性眩晕药物的实验研究。     

Myocardial ischaemia following electrical stimulation of the left circumflex coronary artery in sheep: a role for thromboxane A2?

The electrical stimulation model of thrombus formation was tested on rabbit carotid artery and adapted to sheep left circumflex coronary artery (LCCA). LCCA blood flow, mean arterial pressure (MAP), heart rate (HR) and ECG were monitored continuously and arterial and coronary venous blood samples were taken for radioimmunoassay of thromboxane B2. Stimulation of the LCCA mimicked acute myocardial infarction; reduction in LCCA blood flow preceded a fall in MAP and appearance of ECG abnormalities. Thromboxane B2 levels rose by 126% 35 min after stimulation. These findings support the proposal by other authors that thromboxane plays an important role in the pathogenesis of acute myocardial infarction.     

Effects of intra-coronary administration of leukotriene D4 in the anaesthetized dog

The left anterior descending coronary artery in anaesthetized greyhounds was perfused at constant pressure with blood pumped from the carotid artery. Phasic and mean coronary flow, left ventricular pressure, dP/dt, cardiac output, ECG, heart rate and systemic pressure were measured. Leukotriene (LT) D₄ was administered into the left anterior descending coronary artery as a bolus injection. LTD₄ caused dose-related reductions in coronary flow. Other parameters showed little immediate change although a gradual decrease in left ventricular pressure, dP/dt, cardiac output and systemic pressure occurred after administration of LTD₄. Following intracoronary administration of LTD₄ small surface haemorrhages were observed over the area perfused. The reduction in coronary flow was not inhibited by indomethacin.     

Measurement of the flow in coronary artery bypass grafts

The aim of our study was to measure the flow in coronary artery bypass grafts and to compare the flow between two groups of patients. In group A the arterial revascularization was performed with both internal thoracic arteries using as a Y graft and in group B conventional revascularization using left internal thoracic artery (ITA) attached to the left anterior descending artery (LAD) and venous grafts to the other branches of the left coronary artery was performed. The flow in all grafts was measured at six time points during the operation. The cumulative flow at the end of the operation in the group A (arterial Y graft) was 51.8 +/- 24.5 ml/min and in group B (conventional technique) it was 96.8 +/- 41.1 ml/min (p < 0.05). The flow in left ITA to LAD was similar in both groups (27.3 +/- 15.9 ml/min and 26.3 +/- 16.1 ml/min in group A and B). The flow in right ITA (25.2 +/- 18.4 ml/min) was significantly lower than in venous grafts (72.5 +/- 45.5 ml/min). The calculated flow reserve was 2.2 in group A and 2.1 in group B. We found that the cumulative flow in arterial Y graft was lower in comparison with conventional revascularization. This is due to the lower flow in the right ITA branch of the Y graft compared to venous grafts. However based on clinical results, we can postulate that the flow in the Y graft is sufficient to meet the demand of the myocardium originally supplied by the left coronary artery.     

Spectral and Coherent Analysis of the Relationship between Pulse Wave Forms in the Carotid Artery and Heart Rate

The purpose of this study was the assessment of the parameters of pulse waves in the carotid artery and their relationships with baroreflex-controlled heart rate variability. The early systolic peak (ESP) is closely connected with the filling of the carotid artery, whereas the late systolic peak (LSP) shows the amplitude of the wave reflected from the periphery and affects arterial pressure oscillations activating baroreceptors and changing the heart rate (HR). A cardiac rhythmogram and pulse pressure waves in the carotid artery were continuously recorded for 5 min. ESP and LSP amplitudes (in ml/l) were evaluated in each wave. Patients with coronary artery disease and healthy subjects were examined. Spectrum analysis and assessment of the coherent function between RR intervals, the ESP, and the LSP in the middle frequency band were performed. In healthy subjects, the amplitude of the ESP was higher than that of the LSP, whereas, in patients, the LSP amplitude surpassed that of the ESP. The LSP/ESP ratio was significantly higher in patients, indicating that artery dilation depended more on the reflected wave than on the primary wave. The study revealed that age had the most pronounced effect on the LSP/ESP ratio. Healthy subjects showed the highest age-dependent coherence between the RR interval and the ESP amplitude, whereas in patients this coherence was significantly lower. Measurement of the ESP and LSP amplitudes and their ratio allowed evaluation of vasomotor artery tone. Age and disease produced the maximum effects on the artery tone and decreased the correlation between the changes in the artery tone and the HR in the baroreflex range of frequency regulation.     

Blood flow of the right and left submandibular gland during unilateral carotid artery occlusion in rat: role of nitric oxide

The aim of the present study was to investigate the effect of unilateral carotid artery occlusion on the blood flow of submandibular gland in anesthetized rats and identify the role of nitric oxide (NO) in blood flow changes after the artery occlusion. L-NAME (N omega-nitro-L-arginine-methyl-ester; 10 mg/kg/day, per os) dissolved in tap water was used to block nitric oxide synthase. Glandular blood flow was measured using Sapirstein's indicator (86Rb) distribution technique. In the control animals the blood flow of left (ligated side) submandibular gland was lower than in the right (unligated side) one (right: 76.4+/-15.4 ml/min/100 g, 64.1+/-13.4 ml/min/100 g, p<0.01). The blood flow of submandibular glands decreased in NOS blocked group versus control. The vascular resistance after L-NAME treatment was elevated (control: 11+/-2.3 R/kg, L-NAME: 17.5+/-4.1 R/kg, p<0.001). In L-NAME group the difference between blood flow value of the left and right submandibular gland was significantly lower than in the control group (control: -16%, NAME: -8%, p<0.01). Conclusion: The maintenance of the blood flow in the left submandibular gland during ligation of the left common carotid artery could be due to the good vascular anastomotic system at these regions and adaptation of the submandibular vessels to the decreased perfusion pressure. Nitric oxide may have a role in the regulation of blood flow tinder this condition.     

Ischemic Postconditioning Fails to Protect against Neonatal Cerebral Stroke

The lack of efficient neuroprotective strategies for neonatal stroke could be ascribed to pathogenic ischemic processes differentiating adults and neonates. We explored this hypothesis using a rat model of neonatal ischemia induced by permanent occlusion of the left distal middle cerebral artery combined with 50 min of occlusion of both common carotid arteries (CCA). Postconditioning was performed by repetitive brief release and occlusion (30 s, 1 and/or 5 min) of CCA after 50 min of CCA occlusion. Alternative reperfusion was generated by controlled release of the bilateral CCA occlusion. Blood-flow velocities in the left internal carotid artery were measured using color-coded pulsed Doppler ultrasound imaging. Cortical perfusion was measured using laser Doppler. Cerebrovascular vasoreactivity was evaluated after inhalation with the hypercapnic gas or inhaled nitric oxide (NO). Whatever the type of serial mechanical interruptions of blood flow at reperfusion, postconditioning did not reduce infarct volume after 72 hours. A gradual perfusion was found during early re-flow both in the left internal carotid artery and in the cortical penumbra. The absence of acute hyperemia during early CCA re-flow, and the lack of NO-dependent vasoreactivity in P7 rat brain could in part explain the inefficiency of ischemic postconditioning after ischemia-reperfusion.     

Measurement of bronchial arterial blood flow and bronchovascular resistance in sheep

We studied the bronchial arterial blood flow (Qbr) and bronchial vascular resistance (BVR) in sheep prepared with carotid-bronchial artery shunt. Nine adult sheep were anesthetized, and through a left thoracotomy a heparinized Teflon-tipped Silastic catheter was introduced into the bronchial artery. The other end of the catheter was brought out through the chest wall and through a neck incision was introduced into the carotid artery. A reservoir filled with warm heparinized blood was connected to this shunt. The height of blood column in the reservoir was kept constant at 150 cm by adding more blood. Qbr was measured, after interrupting the carotid-bronchial artery flow, by the changes in the reservoir volume. The bronchial arterial back pressure (Pbr) was measured through the shunt when both carotid-bronchial artery and reservoir Qbr had been temporarily interrupted. The mean Qbr was 34.1 +/- 2.9 (SE) ml/min, Pbr = 17.5 +/- 3.3 cmH2O, BVR = 3.9 +/- 0.5 cmH2O X ml-1 X min, mean pulmonary arterial pressure = 21.5 +/- 3.6 cmH2O, and pulmonary capillary wedge pressure (Ppcw) = 14.3 +/- 3.7 cmH2O. We further studied the effect of increased left atrial pressure on these parameters by inflating a balloon in the left atrium. The left atrial balloon inflation increased Ppcw to 25.3 +/- 3.1 cmH2O, Qbr decreased to 21.8 +/- 2.4 ml/min (P less than 0.05), and BVR increased to 5.5 +/- 1.0 cmH2O.ml-1.min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamics of coronary circulation in rats]

The blood flow velocities in left anterior descending coronary artery and ascending aorta have been measured in anesthetized rats by high frequency Doppler technique. The measurement of coronary blood flow velocity by miniature ultrasonic probe (2.0 x 1.5 mm) was performed through myocardial surface. Two different forms of coronary blood flow curves were recorded. These forms of the curves depend on the value of the coronary blood flow velocity and are connected with the ascending aorta blood flow velocity. The dynamics of the coronary blood flow reactions under coronary artery occlusion and asphyxia in the rat is similar to the one in the cat and the dog, but less expressive. In experiments with vasodilators the direct dependence between linear and volume coronary artery velocities under the measurement through myocardial surface was found.     

超声检查颈动脉粥样硬化情况和肱动脉FMD对稳定性心绞痛的价值

目的：探讨无创超声检查颈动脉粥样硬化情况和肱动脉FMD对SAP的价值。方法：将选取的65例SAP患者分为轻度狭窄组、中度狭窄组和重度狭窄组,超声检测所有病例的肱动脉FMD和颈总动脉IMT,并作Califf危险评分和As积分,分析观察指标间的关系。结果：cati行危险评分和As积分都随着冠脉狭窄程度的加深而增大,且二者呈正相关（P〈0．05）;颈总动脉IMT随着狭窄程度的加深而增大,肱动脉FMD则随着狭窄程度的加深而降低,二者呈负相关（P〈0．05）。结论：无创监测颈总动脉IMT和肱动脉FMD,可指导SAP临床风险的控制。     

Patterns of flow in the left coronary artery

The purpose of this investigation is to describe our preliminary observations of the overall pattern of flow in a mold of the left coronary artery of a pig. Flow in the coronary mold was visualized by the injection of dye into the sinus of Valsalva. Studies were performed during steady flow at rates of 100, 200, 300, 400, and 500 mL/min. Studies were also performed during pulsatile flow, using a pulse duplicator that simulated the magnitude and phasic pattern of coronary flow at rest and during reactive hyperemia. At conditions that simulated rest, mean coronary flow was adjusted to 121 mL/min of which 24 mL/min (20 percent) was systolic. During simulated reactive hyperemia, mean flow was 440 mL/min. Visualization of flow revealed the absence of disturbances of turbulence during both steady and pulsatile flow in the left anterior descending (LAD) and left circumflex (CIRC) coronary arteries throughout the entire range of flow studied. Prominent spiraling of flow occurred during steady and pulsatile flow. Spiraling of flow was not observed in the LAD at rest during pulsatile flow, but developed during simulated reactive hyperemia. Helical flows were observed in the CIRC both during simulated rest and reactive hyperemia. These observations suggest that helical flows may be characteristic features of flow in the left coronary artery; whereas turbulence may not be a feature of this flow field. Whether the spiraling of flow that we observed related to the spiral distribution of early atheroma reported by others, is undetermined.     

新生小鼠缺氧缺血性脑损伤模型的制作研究

目的：通过对动物模型的制作模拟新生儿围产期缺氧缺血性脑损伤,研究其脑组织病理变化,为新生儿缺氧缺血性脑损伤的病理生理的研究以及进一步有效的治疗提供实验基础。方法：将40只7d新生昆明小鼠分四组,分别为正常组（A组）、单侧颈总动脉结扎组（B组）、单侧颈总动脉结扎＋缺氧组（C组）和双侧颈总动脉结扎组（D组）。单侧颈总动脉结扎组（B组）行右侧颈总动脉结扎;单侧颈总动脉结扎＋缺氧组（C组）行右侧颈总动脉结扎后将其置于20℃的恒温50mL密闭容器中,分不同的时间将其取出;双侧颈总动脉结扎组（D组）行双侧颈总动脉结扎,各组术后均送回母鼠身边继续母乳喂养,三天后再作病理检测。结果：行单侧颈总动脉结扎加缺氧60min时,小鼠结扎侧皮质及海马区出现病理改变,随着缺氧时间延长（90rain、100min、120min）病变范围逐渐扩大,病理改变越明显。结论：本实验显示单侧颈总动脉结扎同时缺氧一定时间可以导致小鼠脑组织损伤,脑细胞发生病理改变,且皮层及海马区域的神经细胞对缺氧缺血最为敏感,从而为进一步研究新生儿缺氧缺血性脑损伤提供了较为可靠的模型。     

Increased nonoxidative glycolysis despite continued fatty acid uptake during demand-induced myocardial ischemia

During stress, patients with coronary artery disease frequently fail to increase coronary flow and myocardial oxygen consumption (MVO(2)) in response to a greater demand for oxygen, resulting in "demand-induced" ischemia. We tested the hypothesis that dobutamine infusion with flow restriction stimulates nonoxidative glycolysis without a change in MVO(2) or fatty acid uptake. Measurements were made in the anterior wall of anesthetized open-chest swine hearts (n = 7). The left anterior descending (LAD) coronary artery flow was controlled via an extracorporeal perfusion circuit, and substrate uptake and oxidation were measured with radiotracers. Demand-induced ischemia was produced with intravenous dobutamine (15 microg x kg(-1) x min(-1)) and 20% reduction in LAD flow for 20 min. Despite no change in MVO(2), there was a switch from lactate uptake (5.9 +/- 3.1) to production (74.5 +/- 16.3 micromol/min), glycogen depletion (66%), and increased glucose uptake (105%), but no change in anterior wall power or the index of anterior wall energy efficiency. There was no change in the rate of tracer-measured fatty acid uptake; however, exogenous fatty acid oxidation decreased by 71%. Thus demand-induced ischemia stimulated nonoxidative glycolysis and lactate production, but did not effect fatty acid uptake despite a fall in exogenous fatty acid oxidation.     

冠状动脉旁路移植术桡动脉桥家兔模型的建立

目的建立一个能模拟冠状动脉旁路移植术桡动脉桥情况的模型。方法50只新西兰兔,股动脉与颈总动脉行端侧吻合,两吻合口之间的颈总动脉予以结扎。术后1、3、7、14、56d分别取完整动脉桥,进行肉眼观察,HE染色观察病理变化,弹力纤维染色,计算机测算血管内膜厚度、新生内膜中膜比指数;电镜观察血管内皮细胞变化。结果50只兔成功建立动脉桥,无手术及围手术期死亡,桥血管总通畅率为86％,对通畅的桥血管作形态学观测发现血管移植后7d起至56d内膜增厚有统计学差异。结论本动物模型可以较好地模拟冠状动脉旁路移植术桡动脉桥的情况。     

Prostaglandins modulate baroreflex-induced changes in blood pressure and myocardial function in anesthetized dogs

The purpose of our study was to investigate the role of prostaglandins in the changes in myocardial function and peripheral and coronary vascular resistance which accompany a generalized increase in sympathetic tone caused by carotid baroreflex unloading in the anesthetized dog. Bilateral carotid artery occlusion (BCO) with heart rate held constant by electrical pacing (150 beats/min) resulted in increases in systolic, (33%) diastolic (40%), and mean (35%) arterial pressures, LV systolic pressure (33%) and left ventricular (LV) dP/dt (37%). After blockade of prostaglandin synthesis with indomethacin (N = 11) or meclofenamate (N = 6) the increases in systolic (41%), diastolic (45%), and mean (41%) arterial pressures, LV systolic pressure (39%), LV dP/dt (52%), and cardiac work caused by BCO were significantly greater, in spite of the initially higher baseline values (11-18%) following the administration of the drugs. In contrast, the changes in circumflex coronary blood flow and coronary vascular resistance to BCO were essentially the same before and after inhibition of prostaglandin synthesis. Systemic prostaglandin synthesis may, therefore, play a significant role in the control of systemic arterial pressure and myocardial function, most probably by modulating the release of norepinephrine from adrenergic nerve terminals, without adversely affecting coronary blood flow regulation.     

超声检查颈动脉粥样硬化情况和肱动脉FMD 对稳定性心绞痛的价值

目的:探讨无创超声检查颈动脉粥样硬化情况和肱动脉FMD对SAP的价值。方法:将选取的65例SAP患者分为轻度狭窄组、中度狭窄组和重度狭窄组,超声检测所有病例的肱动脉FMD和颈总动脉IMT,并作Califf危险评分和As积分,分析观察指标间的关系。结果:Califf危险评分和As积分都随着冠脉狭窄程度的加深而增大,且二者呈正相关(P<0.05);颈总动脉IMT随着狭窄程度的加深而增大,肱动脉FMD则随着狭窄程度的加深而降低,二者呈负相关(P<0.05)。结论:无创监测颈总动脉IMT和肱动脉FMD,可指导SAP临床风险的控制。     

Influence of serotonin on myocardial blood flow in the presence and absence of a coronary arterial stenosis: observations in domestic swine

This study tested the hypothesis that 5-HT may impair coronary flow regulation by inappropriately increasing arteriolar tone in the coronary circulation. Ten closed chest, domestic swine were studied both in the presence and in the absence of a severe artificial intraluminal coronary stenosis. A 5-French micromanometer catheter with fluid lumen was placed in the left anterior descending coronary artery and used to record pressure and infuse 5-HT (40 and 100 micrograms/min) into the coronary circulation. For the stenosis phase of the protocol the catheter was embedded in the artificial stenosis. Hemodynamics, regional myocardial blood flow (microsphere technique), coronary vascular resistance, lactate consumption, and oxygen metabolism were measured at control and at 5 min of each 5-HT dose. In the absence of coronary artery stenosis (i.e., full vasodilatory reserve), there was no change in regional myocardial blood flow or coronary vascular resistance during 5-HT infusion. In the presence of a severe coronary stenosis (i.e., limited vasodilator reserve) 5-HT produced a significant (P less than 0.05) decrease versus control in the distal left anterior descending: circumflex zone endocardial blood flow ratio (0.63 +/- 0.19, mean +/- 1 SD, to 0.55 +/- 0.15) and a significant (P less than 0.05) increase versus control in endocardial (50.6 +/- 16.6 to 61.2 +/- 19.8 mm Hg/ml/min/g) and transmural (49.9 +/- 9.5 to 57.2 +/- 12.8) coronary vascular resistance. Thus, 5-HT does not impair coronary flow regulation when full vasodilatory reserve is present. When coronary vasodilatory reserve is impaired by the presence of a severe proximal stenosis, 5-HT causes modest impairment of endocardial flow regulation.     

Systemic circulatory effects of pentagastrin

Effects of pentagastrin on systemic circulation were studied in anesthetized cats. Systemic arterial, central venous and portal pressure were monitored with electromanometers and blood flow through the superior mesenteric artery, common carotid artery, femoral artery and ascending aorta were measured with an electromagnetic blood flow meter. Pentagastrin injected intravenously at a doses of 2.0, 4.0 and 8.0 micrograms/kg induced a dose-dependent fall in arterial pressure, heart rate and cardiac output, increased mesenteric blood flow, decreased common carotid artery blood flow, did not change femoral artery blood flow and slightly rose central venous pressure. Atropine blocked observed effects. After repeated injections of the peptide, tachyphylaxis quickly developed. The obtained results indicate that pentagastrin influences general hemodynamics probably via interaction with cholinergic receptors.