Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex

The aim of this study was to test the hypothesis that, within a specific cortical unit, fractional changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O(2))) are coupled through an invariant relationship during physiological stimulation. This aim was achieved by simultaneously measuring relative changes in these quantities in human primary visual cortex (V1) during graded stimulation with patterns designed to selectively activate different populations of V1 neurons. Primary visual cortex was delineated individually in each subject by using phase-encoded retinotopic mapping. Flow-sensitive alternating inversion recovery MRI, in conjunction with blood oxygenation-sensitive MRI and hypercapnic calibration, was used to monitor CBF and CMR(O(2)). The stimuli used included (i) diffuse isoluminant chromatic displays; (ii) high spatial-frequency achromatic luminance gratings; and (iii) radial checkerboard patterns containing both color and luminance contrast modulated at different temporal rates. Perfusion responses to each pattern were graded by varying luminance and/or color modulation amplitudes. For all stimulus types, fractional changes in blood flow and oxygen uptake were found to be linearly coupled in a consistent ratio of approximately 2:1. The most potent stimulus produced CBF and CMR(O(2)) increases of 48 +/- 5% and 25 +/- 4%, respectively, with no evidence of a plateau for oxygen consumption. Estimation of aerobic ATP yields from the observed CMR(O(2)) increases and comparison with the maximum possible anaerobic ATP contribution indicate that elevated energy demands during brain activation are met largely through oxidative metabolism.     

Effect of hemodilution on maximal oxygen consumption, blood lactate response to exercise and cerebral blood flow in subjects with a high-affinity hemoglobin

Abstract: 10 subjects with Hb Linkdping (β 36 Pro>Thr), a high-affinity hemoglobin variant, with a P₅₀ of 2.2 kPa (16.5 mm Hg) were investigated before and 3–4 days after normovolemic hemodilution. Blood hemoglobin concentration decreased from 176 ± 13 (SD) to 146 ± 15 g 1^-1and the red cell volume from 2.77 ± 0.83 to 2.23 ± 0.67 1. Maximal oxygen consumption decreased slightly by 2.7 ± 3.8 ml min^-1kg^-1and maximal exercise power by 11 ± 23 W; these changes were, however, not statistically significant. Maximal heart rate was unchanged (— 1.1 ± 6.4 beats min^-1) while submaximal heart rate was consistently increased on comparable loads after hemodilution compared to before. The exercise ECG was normal both before and after hemodilution. Capillary lactate levels at exercise were always higher after hemodilution than before. Cerebral blood flow was normal both before and after hemodilution in all subjects but one who had a high flow. The grey matter blood flow increased slightly but significantly by 8.6 ± 10.3 ml min^-1100 g^-1from before to after hemodilution. The results indicate that subjects with Hb Linkoping have only limited benefit from their increased blood hemoglobin concentration.     

体外循环期间不同血气管理方法对脑组织血流和氧代谢的影响

目的:比较两种血气管理方法,对中浅低温双瓣膜置换体外循环期间,大脑血流速度和氧代谢的影响。方法:选取连续24例中浅低温体外循环下行双瓣膜置换患者,使用CDI500进行连续血气监测。分别于以下5个时间点:麻醉诱导后(T1),体外循环转机10min时(T2),当鼻咽温降至25℃时,使用α稳态管理并校正血气15min后(T3),后改用pH稳态管理并校正血气15min后(T4),停机后10min(T5),使用经颅多普勒超声仪和近红外线光谱仪,测定大脑中动脉血流速度和脑氧饱和度,评估不同血气管理方法的脑保护效果。结果:与T1相比较,T2、T3脑血流速度和脑氧饱和度均有所减少,但差异无统计学意义(P0.05)。与T3相比较,T4时间点大脑血流速度和脑氧饱和度稍有升高,但差异并无统计学意义(P0.05)。结论:中浅低温体外循环期采用pH稳态血气管理并未明显增加大脑血流速度和氧供。     

Mapping of cerebral oxidative metabolism with MRI

Using a T_1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of gas. The study was performed by inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9%+/-2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T_1ρ MRI following administration of gas. Metabolism was calculated from the change in the T_1ρ weighted MRI signal due to H₂¹⁷O generated from inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H₂¹⁷O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive gas. Given the demonstrated high efficiency in use of and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.     

Magnitude and duration of excess of post‐exercise oxygen consumption between high‐intensity interval and moderate‐intensity continuous exercise: A systematic review

The present systematic review examined the effect of exercise intensity (high‐intensity interval exercise [HIIE] vs. moderate‐intensity continuous exercise [MICE] vs. sprint interval exercise [SIE]) on excess post‐exercise oxygen consumption (EPOC). Twenty‐two studies were included in the final evaluation. The retrieved investigations were split into studies that analysed short‐duration (until 3 h) and long‐duration (more than 3 h) EPOC. Studies that subtracted the baseline energy expenditure (EE) were analysed separately from those that did not. Most short‐duration evaluations that subtracted baseline EE reported higher EPOC for HIIE (average of ~136 kJ) compared with MICE (average of ~101 kJ) and higher values for SIE (average of ~241 kJ) compared with MICE (average of ~151 kJ). The long‐duration evaluations resulted in greater EPOC for HIIE (average of ~289 kJ) compared with MICE (average of ~159 kJ), while no studies comparing SIE versus MICE provided appropriate values. EE from EPOC seems to be greater following HIIE and SIE compared with MICE, and long‐duration evaluations seem to present higher values than short‐duration evaluations. Additionally, more standardized methodologies are needed in order to determine the effective EPOC time following these protocols.     

Top-down attention switches coupling between low-level and high-level areas of human visual cortex

Top-down attention is an essential cognitive ability, allowing our finite brains to process complex natural environments by prioritizing information relevant to our goals. Previous evidence suggests that top-down attention operates by modulating stimulus-evoked neural activity within visual areas specialized for processing goal-relevant information. We show that top-down attention also has a separate influence on the background coupling between visual areas: adopting different attentional goals resulted in specific patterns of noise correlations in the visual system, whereby intrinsic activity in the same set of low-level areas was shared with only those high-level areas relevant to the current goal. These changes occurred independently of evoked activity, persisted without visual stimulation, and predicted behavioral success in deploying attention better than the modulation of evoked activity. This attentional switching of background connectivity suggests that attention may help synchronize different levels of the visual processing hierarchy, forming state-dependent functional pathways in human visual cortex to prioritize goal-relevant information.     

常压氧联合高压氧对急性脑梗死患者血清细胞间黏附分子及基质金属蛋白酶-9的影响

目的：探讨常压氧（NBO）联合高压氧（HBO）对急性脑梗死血清细胞间黏附分子及基质金属蛋白酶-9（MMP-9）水平的影响。方法选择2011年12月至2014年3月在青岛市中心医院神经内科住院且发病24h内来院就诊的168例急性脑梗死患者为急性脑梗死组,将其随机分为常规治疗、HBO治疗及NBO联合HBO治疗3个亚组,分别在治疗前、治疗10d后采用酶联免疫吸附法（ELISA）测定各亚组血清可溶性细胞间黏附分子（sICAM-1）、可溶性E-选择素（sE-selectin,sES）及MMP-9水平,分析各亚组治疗前后神经功能缺损变化。另以50名正常人组成正常对照组。结果3个亚组治疗10d后,血清sICAM-1、sES和MMP-9水平分别较治疗前显著下降（t＝8.754-11.351,P＜0.01）;HBO亚组、NBO＋HBO亚组患者显著低于常规亚组（t＝2.237-4.162,P＜0.05或0.01）;与HBO亚组比较,NBO＋HBO亚组患者血清sICAM-1、sES和MMP-9水平均显著下降（t＝2.141-2.366,P＜0.01）;HBO亚组、NBO＋HBO亚组治疗10d后,NIHSS评分较常规亚组显著下降（t＝5.367,P＜0.01;t＝9.943,P＜0.01）,而NBO＋HBO亚组较HBO亚组治疗后NIHSS评分显著下降,差异具有统计学意义（t＝2.827,P＜0.01）。结论 NBO联合HBO治疗抑制血清sICAM-1、sES和MMP-9水平优于HBO亚组,且更能改善急性脑梗死患者临床预后。     

超声检测大脑中动脉慢性闭塞患者脑血流与脑梗死的相关性

目的探讨大脑中动脉慢性闭塞(CMCAO)患者大脑前动脉(ACA)脑膜支代偿(LMA)对脑梗死大小的影响,分析大脑中动脉(MCA)流速与脑梗死面积的相关性。方法回顾性连续纳入2014年6月至2016年6月延边大学附属医院神经内科35例和首都医科大学宣武医院神经内科的CMCAO患者74例,对所有患者采用经颅多普勒超声(TCD)和(或)经颅彩色多普勒超声(TCCS)诊断为一侧CMCAO而对侧MCA正常,并经DSA证实。根据DSA显示ACA有无脑膜支,分为LMA组49例及无LMA组(NLMA)60例。采用TCCS和(或)TCD测量,记录患侧与健侧MCA的收缩期峰值流速(PSV)及平均流速(MFV),并计算健侧、患侧PSV比值(PSV_(健侧)/PSV_(患侧))。根据磁共振扩散加权成像(DWI)检查结果分为脑组织正常、腔隙性脑梗死、中小面积脑梗死及大面积脑梗死4级,采用秩和检验比较LMA组与NLMA组脑梗死面积的差异,并采用Spearman秩相关分析患侧MCA的血流参数与脑梗死面积的相关性。结果 (1)两组患者的患侧与健侧MCA的PSV、MFV及PSV_(健侧)/PSV_(患侧)差异均无统计学意义(均P0.05)。(2)NLMA组中卒中者占90.0%(54例),明显高于LAM组71.4%(35例),两组间差异有统计学意义(P0.05);LMA组DWI以腔隙性脑梗死为主(51.0%,25例),NLMA组多以中小面积脑梗死为主(45.0%,27例),并且大面积脑梗死发生率(21.7%,13例)高于LMA组(4.1%,2例),两组差异有统计学意义(P0.01)。(3)NLMA组患者脑梗死面积与MCA的PSV呈中度负相关(r=-0.736,P0.01),并随PSV_(健侧)/PSV_(患侧)的升高而增加,呈高度正相关(r=0.849,P0.01)。结论 CMCAO患者ACA的LMA状态与脑梗死严重程度相关,患侧MCA血流速度的减低与脑梗死面积存在明显相关性。     

Symmetry of cerebral blood flow and cognitive responses to hypoglycaemia in humans

Summary A low blood glucose level is associated with impairment of higher cerebral function and an increase in cerebral blood flow. This study examined whether there are differences in the physiological responses to hypoglycaemia between the cerebral hemispheres. Eight healthy men participated in two hyperinsulinaemic glucose clamp studies: after 60 min at 4.5 mmol/l, blood glucose was either lowered to 2.0 mmol/l and clamped there for 60 min (hypoglycaemia) or continuously maintained at 4.5 mmol/l (euglycaemia). Cardiac output, middle cerebral artery velocity (transcranial Doppler) and cerebral blood flow (133-xenon inhalation) were measured during the studies. Neuropsychological tests were used to determine whether hypoglycaemia caused differential impairment of hemispheric cognitive function. Hypoglycaemia was associated with symmetrical impairment of cognitive function in both cerebral hemispheres and a rise in cardiac output (from 5.5 [0.2] to 8.7 [0.2] l · min^–1 p<0.0001, mean [standard error]), middle cerebral artery velocity (from 55 [2.6] to 64 [2.8] cm·s^–1, p<0.002), and global cerebral blood flow (from 56 [2.6] to 69 [2.9] ml·100 g^–1·min^–1, p<0.005 compared to pre-insulin values). There were no differences in the blood flow response during hypoglycaemia between hemispheres and the increase in blood flow did not correlate with either the change in cardiac output or rise in plasma catecholamine levels. After 120 min of hyperinsulinaemic, euglycaemia, global cerebral blood flow rose significantly above baseline (from 58 [2.4] to 63 [2.2] ml·100 g^–1·min^–1, p<0.05). In conclusion, using the techniques described, the physiological and cognitive responses of each cerebral hemisphere to hypoglycaemia were symmetrical. Hyperinsulinaemia, independent of blood glucose level, may be associated with an increase in cerebral blood flow.     

Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production

Abstract:  The role of melatonin in improving mitochondrial respiratory chain activity and increasing ATP production in different experimental conditions has been widely reported. To date, however, the mechanism(s) involved are largely unknown. Using high-resolution respirometry, fluorometry and spectrophotometry we studied the effects of melatonin on normal mitochondrial functions. Mitochondria were recovered from mouse liver cells and incubated in vitro with melatonin at concentrations ranging from 1 n m to 1 m m . Melatonin decreased oxygen consumption concomitantly with its concentration, inhibited any increase in oxygen flux in the presence of an excess of ADP, reduced the membrane potential, and consequently inhibited the production of superoxide anion and hydrogen peroxide. At the same time it maintained the efficiency of oxidative phosphorylation and ATP synthesis while increasing the activity of the respiratory complexes (mainly complexes I, III, and IV). The effects of melatonin appeared to be due to its presence within the mitochondria, since kinetic experiments clearly showed its incorporation into these organelles. Our results support the hypothesis that melatonin, together with hormones such as triiodothyronine, participates in the physiological regulation of mitochondrial homeostasis.     

无症状脑梗死认知功能障碍与脑血流灌注的关系

目的 探讨无症状脑梗死（SCI）患者认知障碍与脑血流灌注的关系.方法 32例SCI患者和21例健康对照组分别完成简易精神状态检查量表（MMSE）、临床痴呆评定量表（CDR）的评定及SPECT脑血流灌注检测,比较两组中轻度认知障碍（MCI）的发生率,并分析各组脑血流灌注的特点.结果 SCI组中MCI的发生率为34.37%,明显高于对照组的14.28%（P＜0.01）.SCI患者的脑血流灌注在双侧颞叶、顶叶、额叶及基底节区明显减低（P＜0.05,P＜0.01）,其中MCI组双侧颞叶、顶叶的脑血流灌注明显低于非MCI组.相关分析显示MCI组MMSE分值与双侧顶叶及左侧颞叶脑灌注呈正相关.结论 SCI可以明显提高MCI的发生,脑血流灌注减低在MCI的发病机制中可能起重要作用.     

Effects of phenytoin on regional cerebral blood flow, electroencephalogram, and electrolyte contents in cerebral blood and cerebral cortex following total cerebral ischemia in dogs

To study the protective effect of phenytoin on postischemic brain damage, total cerebral ischemia was produced for 8-12 min (aortic occlusion balloon catheter method) in 36 adult mongrel dogs. The regional cerebral blood flow (rCBF), sodium:potassium ratio in the cerebral cortex, electroencephalogram (EEG), and plasma electrolytes in the superior sagittal sinus blood were examined before ischemia and during the acute stage up to 120 min after recirculation in the control and phenytoin-treated groups. Measurement of rCBF (microsphere method) indicated easing of postischemic hypoperfusion of the cerebral cortex. The time from total cerebral ischemia to EEG electrical silence was significantly prolonged, and recovery of the electrical activity after recirculation was hastened. The increase in plasma potassium concentration in the superior sagittal sinus tended to be suppressed immediately after recirculation, and the sodium:potassium ratio in the cerebral cortex was lowered. Phenytoin increased the rCBF in the cerebral cortex, hastened the recovery of electrical activity, and stabilized the water and electrolyte balance in the cerebral cortex, suggesting some protecting effect on total cerebral ischemia.     

术中局部脑氧饱和度水平与老年全身麻醉术后谵妄发生的关系

目的探讨术中局部脑氧饱和度(rSO2)的变化与老年患者全麻手术后发生谵妄的关系。方法选择2017年1月至2018年1月内蒙古医科大学附属医院麻醉科收治的老年全麻脊柱手术患者76例。患者入室后持续监测rSO2,并记录麻醉诱导前(T0)、气管插管后(T1)、手术开始时(T2)、手术开始后1 h(T3)、手术开始后2 h(T4)、术毕(T5)时的rSO2、心率(HR)及平均动脉压(MAP)。以患者T0时的rSO2值作为基线值,计算T0~T5的rSO2平均值(rSO2)、最小值(rSO2min)和较基线值下降的最大差值(ΔrSO2max)。采用意识紊乱测试法(CAM)对术后患者认知状态进行评估,并分为术后谵妄组(POD组,14例)和非术后谵妄组(NPOD组,62例),同时比较2组上述指标。采用SPSS 18.0软件对数据进行分析。组间比较采用t检验,组内比较采用重复测量的方差分析或两两比较。结果POD发生率为18.4%(14/76)。2组患者T0~T5的MAP及HR比较差异均无统计学意义(P>0.05)。T0~T3的rSO2在2组间比较无明显差异(P>0.05);T4、T5时,相比NPOD组,POD组患者rSO2值明显下降(P<0.05)。与NPOD组比较,POD组患者ΔrSO2max显著升高[(0.09±0.04)%和(0.05±0.02)%],rSO2显著降低[(73.29±1.69)%和(75.49±1.89)%],但rSO2min[(65.00±3.40)%和(67.47±5.10)%]及基线值[(71.14±0.77)%和(70.95±0.89)%]比较差异无统计学意义(P>0.05)。结论术中rSO2的降低与POD的发生有明显相关性,术中监测rSO2可作为预测POD发生的辅助手段。     

The measurement of heat production,mechanical power,and oxygen consumption of the isolated working rat heart

Summary The article describes a method for monitoring the total energy output and oxygen uptake of isolated perfused rat hearts with working left ventricles. Twenty-two unpaced hearts (rates 4–4.5 bs^–1) were separately investigated inside a flow micro-calorimeter (one minute for 90% thermal response) at 37°C. They pumped fluid into an artificial arterial system with adjustable linear peripheral resistance and variable volume complicance. After about 20–40 minutes a steady state period was achieved and most of the hearts continued to operate in this state for a further 40–100 minutes. In the steady state the outputs were in the ranges of 30–50 mJ s^–1g^–1 mechanical power (per gram tissue dry weight) and 100–300 mJ s^–1g^–1 heat production at an oxygen uptake of between 0.01 and 0.02 cm³ O₂ s^–1g^–1. This resulted in approximately constant cardiac outputs between 2 and 4 cm³s^–1g^–1 aortic and coronary fluid and stable mechanical efficiencies between 12 and 20%. The energy balance in steady state under a number of defined arterial loads was also analyzed. The hearts attained reproducible maxima of mechanical efficiency at specific loads. Methods to allocate reference points in the energy scheme are discussed. The yield of biochemical energy from the perfusion fluid (utilized for contraction and heart production) was (on average) 21 J per cm³ oxygen consumption (energy equivalent of oxygen). No obvious correlation between this value and the mechanical efficiency was evident.     

Comparative study of cerebral blood flow between postural tachycardia and neurocardiogenic syncope, during head-up tilt test.

We assessed the cerebral blood flow velocity response to head-up tilt test in patients with typical neurocardiogenic syncope compared with patients showing postural tachycardia. Fifty patients (21 men) with history of orthostatic intolerance, younger than 50 years (mean 27 +/- 10), participated in the study. Transcranial Doppler sonography of the middle cerebral artery, heart rate and brachial blood pressure were recorded during a head-up tilt test. According to the outcome of the test, patients were categorized in two groups: neurocardiogenic syncope (29 patients) and postural tachycardia (21 patients). The clinical history of the two groups was similar. During baseline in the supine position, no differences in haemodynamic parameters were observed. From the first min of tilt, the heart rate was higher in patients with postural tachycardia than in patients with neurocardiogenic syncope. Although, during tilt, the absolute values of the cerebral blood flow parameters were similar in the two groups, throughout tilt, continuous observation of the Doppler recording in patients with postural tachycardia showed intermittent fluctuation of the blood flow velocity, with an oscillatory pattern, which were not observed in the recordings in patients with neurocardiogenic syncope. Comparison of patients with neurocardiogenic syncope, and those with postural tachycardia also showed larger variations of the pulsatility index (P < 0.05) in the postural tachycardia group. These findings support the possibility that abnormalities within the central nervous system play a pivotal role in the pathogenesis of postural tachycardia.