Instability of the Middle Cerebral Artery Blood Flow in Response to CO2

Background

The middle cerebral artery supplies long end-artery branches to perfuse the deep white matter and shorter peripheral branches to perfuse cortical and subcortical tissues. A generalized vasodilatory stimulus such as carbon dioxide not only results in an increase in flow to these various tissue beds but also redistribution among them. We employed a fast step increase in carbon dioxide to detect the dynamics of the cerebral blood flow response.

Methodology/Principal Findings

The study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. We used transcranial ultrasound to measure the time course of middle cerebral artery blood flow velocity in 28 healthy adults. Normoxic, isoxic step increases in arterial carbon dioxide tension of 10 mmHg from both hypocapnic and normocapnic baselines were produced using a new prospective targeting system that enabled a more rapid step change than has been previously achievable. In most of the 28 subjects the responses at both carbon dioxide ranges were characterised by more complex responses than a single exponential rise. Most responses were characterised by a fast initial response which then declined rapidly to a nadir, followed by a slower secondary response, with some showing oscillations before stabilising.

Conclusions/Significance

A rapid step increase in carbon dioxide tension is capable of inducing instability in the cerebral blood flow control system. These dynamic aspects of the cerebral blood flow responses to rapid changes in carbon dioxide must be taken into account when using transcranial blood flow velocity in a single artery segment to measure cerebrovascular reactivity.     

The Effects of Involuntary Respiratory Contractions on Cerebral Blood Flow during Maximal Apnoea in Trained Divers

The effects of involuntary respiratory contractions on the cerebral blood flow response to maximal apnoea is presently unclear. We hypothesised that while respiratory contractions may augment left ventricular stroke volume, cardiac output and ultimately cerebral blood flow during the struggle phase, these contractions would simultaneously cause marked ‘respiratory’ variability in blood flow to the brain. Respiratory, cardiovascular and cerebrovascular parameters were measured in ten trained, male apnoea divers during maximal ‘dry’ breath holding. Intrathoracic pressure was estimated via oesophageal pressure. Left ventricular stroke volume, cardiac output and mean arterial pressure were monitored using finger photoplethysmography, and cerebral blood flow velocity was obtained using transcranial ultrasound. The increasingly negative inspiratory intrathoracic pressure swings of the struggle phase significantly influenced the rise in left ventricular stroke volume (R ² = 0.63, P<0.05), thereby contributing to the increase in cerebral blood flow velocity throughout this phase of apnoea. However, these contractions also caused marked respiratory variability in left ventricular stroke volume, cardiac output, mean arterial pressure and cerebral blood flow velocity during the struggle phase (R ² = 0.99, P<0.05). Interestingly, the magnitude of respiratory variability in cerebral blood flow velocity was inversely correlated with struggle phase duration (R ² = 0.71, P<0.05). This study confirms the hypothesis that, on the one hand, involuntary respiratory contractions facilitate cerebral haemodynamics during the struggle phase while, on the other, these contractions produce marked respiratory variability in blood flow to the brain. In addition, our findings indicate that such variability in cerebral blood flow negatively impacts on struggle phase duration, and thus impairs breath holding performance.     

低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响

Nrf2可调节多种抗氧化酶的表达,Nrf2的缺失可能影响机体的运动能力,而低氧可提高机体的抗氧化能力并改善运动能力。为了考察低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响,本研究分别在常氧和低氧环境(12%氧浓度)中对野生型大鼠和Nrf2敲除大鼠进行4周的跑台运动。研究显示,低氧运动可提高野生型大鼠的跑台运动力竭时间,Nrf2敲除可缩短大鼠的力竭时间;低氧运动可上调大鼠的Nrf2 m RNA表达量;Nrf2敲除明显抑制HIF-1α蛋白表达,而低氧运动可上调野生型和Nrf2敲除大鼠的HIF-1α蛋白表达;Nrf2敲除大鼠的骨骼肌ROS水平明显升高,并且低氧均可降低野生型和Nrf2敲除大鼠骨骼肌ROS水平。低氧运动可上调Nrf2敲除大鼠的CAT和GSH-PX蛋白表达。苏木精和伊红(HE)染色显示,Nrf2敲除大鼠在力竭跑台运动完成后出现更严重的骨骼肌病理改变,而低氧运动可减轻骨骼肌损伤。本研究认为,Nrf2敲除导致了大鼠骨骼肌中抗氧化酶的抑制及ROS的过量累积,从而造成了骨骼肌损伤并降低了运动能力。此外,低氧可通过上调Nrf2的表达,进而激活HIF-1α及抗氧化酶活性,从而提高运动能力,并防止骨骼肌损伤。     

The Effect of Morphine on Regional Cerebral Blood Flow Measured by 99mTc-ECD SPECT in Dogs

To gain insights into the working mechanism of morphine, regional cerebral blood flow (rCBF) patterns after morphine administration were assessed in dogs. In a randomized cross-over experimental study, rCBF was estimated with ^99mTc-Ethylcysteinate Dimer single photon emission computed tomography in 8 dogs at baseline, at 30 minutes and at 120 minutes after a single bolus of morphine. Perfusion indices (PI) in the frontal, parietal, temporal and occipital cortex and in the subcortical and cerebellar region were calculated. PI was significantly decreased 30 min after morphine compared to baseline in the right frontal cortex. The left parietal cortex and subcortical region showed a significantly increased PI 30 min after morphine compared to baseline. No significant differences were noted for the other regions or at other time points. In conclusion, a single bolus of morphine generated a changing rCBF pattern at different time points.     

The Effect of Lipemia on Peripheral Blood Flow

The effect of lipemia on peripheral blood flow was studied in patients with and without peripheral vascular disease. Blood flow was measured by venous occlusion plethysmography in the calf and/or finger four to six hours after a fatty meal and after intravenous heparin. The abolition of postprandial lipemia by heparin was determined by measuring the plasma lactescence.Heparin resulted in no change in finger flow of either group or in calf flow in the control group. In nine out of 10 patients with occlusive vascular disease of the legs, it resulted in a small but significant increase of calf blood flow. No such alteration was found when heparin was given following a non-fatty meal.In 12 patients with intermittent claudication the clearing of postprandial lipemia by heparin caused prolongation of claudication time, as measured by the appearance of pain on treadmill exercise.It is concluded that, in some cases, postprandial lipemia is associated with a decrease in blood flow in a limb which is already the site of occlusive vascular disease.     

Effect of Acute Inspiratory Muscle Exercise on Blood Flow of Resting and Exercising Limbs and Glucose Levels in Type 2 Diabetes

To evaluate the effects of inspiratory loading on blood flow of resting and exercising limbs in patients with diabetic autonomic neuropathy. Ten diabetic patients without cardiovascular autonomic neuropathy (DM), 10 patients with cardiovascular autonomic neuropathy (DM-CAN) and 10 healthy controls (C) were randomly assigned to inspiratory muscle load of 60% or 2% of maximal inspiratory pressure (PImax) for approximately 5 min, while resting calf blood flow (CBF) and exercising forearm blood flow (FBF) were measured. Reactive hyperemia was also evaluated. From the 20 diabetic patients initially allocated, 6 wore a continuous glucose monitoring system to evaluate the glucose levels during these two sessions (2%, placebo or 60%, inspiratory muscle metaboreflex). Mean age was 58 ± 8 years, and mean HbA1c, 7.8% (62 mmol/mol) (DM and DM-CAN). A PImax of 60% caused reduction of CBF in DM-CAN and DM (P<0.001), but not in C, whereas calf vascular resistance (CVR) increased in DM-CAN and DM (P<0.001), but not in C. The increase in FBF during forearm exercise was blunted during 60% of PImax in DM-CAN and DM, and augmented in C (P<0.001). Glucose levels decreased by 40 ± 18.8% (P<0.001) at 60%, but not at 2%, of PImax. A negative correlation was observed between reactive hyperemia and changes in CVR (Beta coefficient = -0.44, P = 0.034). Inspiratory muscle loading caused an exacerbation of the inspiratory muscle metaboreflex in patients with diabetes, regardless of the presence of neuropathy, but influenced by endothelial dysfunction. High-intensity exercise that recruits the diaphragm can abruptly reduce glucose levels.     

The Effect of Exercise on Blood Parameters in Standardbred and Finnish-Bred Horses

Serum enzyme activities, albumin, protein, urea, cholesterol, triglyceride, free fatty acid, glucose and lactate concentrations as well as hematocrit values were measured in standardbred and Finnish-bred horses at rest and after (i) a short controlled exercise and (ii) a trotting competition. There were no breed differences in the enzyme activities at rest and the 2 breeds responded in the same manner to the exercise. Only after the race proper significant increases in the enzyme activities were found. The activities rose more in the standardbred horses than in the Finnish-bred horses. Urea and cholesterol concentrations did not change after either exercise. Protein and albumin concentrations as well as hematocrit values increased significantly after the exercise. At rest hematocrit values were significantly higher in the standardbred horses and the difference persisted throughout the exercise. After the race proper also albumin and protein concentrations were higher in the standard-bred than in the Finnish-bred horses. Free fatty acid and triglyceride concentrations increased significantly during the exercise. Although glucose and lactate concentrations increased in both breeds, the behaviour of these parameters differed. Glucose concentrations remained increased for a longer period and the recovery from the increased lactate level was faster in the standardbred than in the Finnish-bred horses. The observed differences suggest that the standardbred horses have higher anaerobic capacity than the Finnish-bred horses.     

Effects of Metabotropic Glutamate Receptor Stimulation on Cerebral O2 Consumption and Blood Flow During Focal Cerebral Ischemia in Rats

This investigation was performed to evaluate the effects of ACPD [(1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid], a metabotropic glutamate receptor agonist, on cerebral O₂ consumption during focal cerebral ischemia. Male Wistar rats were placed in control (n = 7) and ACPD (n = 7) groups under isoflurane anesthesia. Twenty minutes after middle cerebral artery (MCA) occlusion, gauze sponges with 10^–5 M ACPD or normal saline were placed on the ischemic cortex (IC) for a period of 40 min and were changed every 10 min. One hour after MCA occlusion, regional cerebral blood flow (rCBF) was determined using the C¹⁴-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined using microspectrophotometry. There were no statistical differences in vital signs, blood gases, and hemoglobin between the groups. In the control group, the cerebral blood flow and oxygen consumption of the IC were significantly lower than the contralateral cortex (rCBF: 45 ± 11 vs. 110 ± 11 ml/min/100 g, O₂ consumption: 2.9 ± 0.4 vs. 5.4 ± 1.1 ml O₂/min/100 g). ACPD did not change regional cerebral blood flow of the IC, but did significantly increase the oxygen extraction (7.8 ± 0.2 vs. 6.9 ± 0.3 ml O₂/100 ml) and oxygen consumption of the IC (4.3 ± 1.5 vs. 2.9 ± 0.4) compared to the control IC. Our data demonstrated that topical application of 10^–25 M ACPD to the ischemic area worsened cerebral O₂ balance. These data suggest that metabotropic glutamate receptors are not maximally activated during ischemia in the temporal cortex.     

腹式呼吸训练法对COPD伴Ⅱ型呼吸衰竭患者肺通气状态、血气指标及运动耐力的影响

摘要 目的：探讨腹式呼吸训练法对慢性阻塞性肺疾病（COPD）伴Ⅱ型呼吸衰竭患者肺通气状态、血气指标及运动耐力的影响。方法：选择我院2020年07月2022年12月期间收治的100例COPD伴Ⅱ型呼吸衰竭患者,根据随机数字表法将患者分为对照组[常规治疗基础上接受双水平气道正压（BIPAP）辅助通气,n=50]和研究组（对照组的基础上接受腹式呼吸训练法干预,n=50）。对比两组临床相关指标、肺通气状态、血气指标及运动耐力指标。结果：研究组的喘憋消失时间、体温恢复正常时间、住院时间、肺部啰音消失时间短于对照组（P<0.05）。两组干预1周后第1秒呼气的最大容积（FEV₁）、最大自主分钟通气量（MVV）、用力肺活量（FVC）均升高,且研究组高于对照组（P<0.05）。两组干预1周后氧分压（PaO2₂）、血氧饱和度（SpO₂）均升高,且研究组高于对照组;二氧化碳分压（PaCO₂）下降,且研究组低于对照组（P<0.05）。两组干预1周后6 min步行距离（6MWT）升高,且研究组高于对照组（P<0.05）。结论：腹式呼吸训练法有助于改善COPD伴Ⅱ型呼吸衰竭患者的临床症状,调节肺通气状态、血气指标,提高运动耐力。     

HTEA对全脑缺血/再灌注大鼠脑血流及海马细胞凋亡的影响

目的:研究上胸段硬膜外阻滞(high thoracic epidural anesthesia,HTEA)对大鼠全脑缺血再灌注损伤(global cerebral ischemia,GCI)再灌注期间脑血流及凋亡相关蛋白Bcl-2和Bax的影响。方法:本研究选用成年雄性Wistar大鼠成功进行T4-5间隙硬膜外置管,并建立四血管阻断的全脑缺血模型进行15 min的全脑缺血。根据通过硬膜外导管输注药物不同,随机分为四组:假手术组(Sham,0.9%生理盐水)、假手术-硬膜外组(Sham-HTEA,0.25%布比卡因)、全脑缺血组(GCI,0.9%生理盐水)和硬膜外组(HTEA,0.25%布比卡因)。给药时间从缺血前15 min开始以20μL/h的速度持续输注至再灌注24 h。缺血前至再灌注2 h观察平均动脉压(MAP)和心率(HR),激光多普勒血流仪监测脑血流(cerebral blood flow,CBF),Western-blot检测再灌注24 h海马凋亡蛋白Bcl-2和Bax含量。结果:HTEA组与GCI组相比,缺血期间及再灌注2 h内的MAP和HR无统计学差异,而与Sham组相比,GCI组的MAP缺血时升高,而再灌注时降低(P0.05);再灌注10 min的高灌注期HTEA组CBF明显低于GCI组(123.1%±35.2%vs 177.5%±32.4%,P0.01),再灌注60 min至120 min的低灌注期的大部分时间点HTEA组CBF均高于GCI组(P0.05);再灌注24 h海马组织Bax/Bcl-2比例明显降低(P0.01)。结论:0.25%的布比卡因20μL·h-1连续上胸段硬膜外阻滞可以维持血流动力学稳定,且可改善大鼠全脑缺血再灌注后低灌注期的脑血流量,并减少再灌注24 h海马Bax/Bcl-2比例。     

The Direct Effect of Increased CO2 on Gas Exchange and Growth of Forest Tree Species

CO₂ enrichment of the atmosphere is now well documented andits effect on the growth of world forests is being questionedby the scientific community. The direct effects of increasedCO₂ on tree species are reviewed: the different experimentalapproaches are described, as well as the principal results alreadyobtained. Short-term experiments have shown an increased photosyntheticrate, as predicted by leaf models. In longer experiments thisincrease is reduced after a few weeks or months by mechanismsthat remain to be found. Elevated CO₂ seems to decrease thedark respiration rate, but the results are still controversial.Biomass partitioning in elevated CO₂ is clearly related to themineral supply of the trees: An increase in root investmentin elevated CO₂ is related to a poor mineral status. The mineralcontent of trees grown in elevated CO2 is generally loweredcompared to controls. No general rule has yet been found forthe effect of increased CO₂ on leaf area development. The paper emphasizes large areas of ignorance: the reasons forthe different responses of different species, which may be relatedto their developmental strategies, are largely ignored. Muchexperimental effort is needed to parameterize all the physiologicalprocesses which are susceptible to change with an increase inatmospheric CO₂, leading to a change in forest tree growth. Key words: Elevated CO₂, tree, forest, photosynthesis, respiration, biomass, partitioning, mineral nutrition     

Influence of Acute Jugular Vein Compression on the Cerebral Blood Flow Velocity,Pial Artery Pulsation and Width of Subarachnoid Space in Humans

Purpose

The aim of this study was to assess the effect of acute bilateral jugular vein compression on: (1) pial artery pulsation (cc-TQ); (2) cerebral blood flow velocity (CBFV); (3) peripheral blood pressure; and (4) possible relations between mentioned parameters.

Methods

Experiments were performed on a group of 32 healthy 19–30 years old male subjects. cc-TQ and the subarachnoid width (sas-TQ) were measured using near-infrared transillumination/backscattering sounding (NIR-T/BSS), CBFV in the left anterior cerebral artery using transcranial Doppler, blood pressure was measured using Finapres, while end-tidal CO₂ was measured using medical gas analyser. Bilateral jugular vein compression was achieved with the use of a sphygmomanometer held on the neck of the participant and pumped at the pressure of 40 mmHg, and was performed in the bend-over (BOPT) and swayed to the back (initial) position.

Results

In the first group (n = 10) during BOPT, sas-TQ and pulse pressure (PP) decreased (−17.6% and −17.9%, respectively) and CBFV increased (+35.0%), while cc-TQ did not change (+1.91%). In the second group, in the initial position (n = 22) cc-TQ and CBFV increased (106.6% and 20.1%, respectively), while sas-TQ and PP decreases were not statistically significant (−15.5% and −9.0%, respectively). End-tidal CO₂ remained stable during BOPT and venous compression in both groups. Significant interdependence between changes in cc-TQ and PP after bilateral jugular vein compression in the initial position was found (r = −0.74).

Conclusions

Acute bilateral jugular venous insufficiency leads to hyperkinetic cerebral circulation characterised by augmented pial artery pulsation and CBFV and direct transmission of PP into the brain microcirculation. The Windkessel effect with impaired jugular outflow and more likely increased intracranial pressure is described. This study clarifies the potential mechanism linking jugular outflow insufficiency with arterial small vessel cerebral disease.     

Effect of Osmotic Stabilizers on 14CO2 Production by Bacteria and Blood

Evolution of (14)CO(2) by whole blood as well as by Diplococcus pneumoniae, Haemophilus sp., Pseudomonas aeruginosa, Pseudomonas diminuta, and Streptococcus pyogenes was examined by using the BACTEC system. The control medium was JLI no. 6A culture vial containing 30 ml of enriched tryptic soy broth and 1.5 muCi of (14)C-substrate. Hypertonic media consisted of control medium with either 1 or 3% NaCl, 10% sucrose, and 5%, 10%, or 15% dextran. The most deleterious treatment to bacteria was 3% NaCl since it not only retarded (14)CO(2) production, but also prevented growth of D. pneumoniae, Haemophilus, and P. diminuta. The 10% sucrose treatment diminished (14)CO(2) output, although it did not retard growth of test organisms. This effect was probably due to (14)C-substrate dilution rather than to osmotic effects. Dextran had slight effect on (14)CO(2) production and slightly acidified the medium. Of the treatments tested, only 10% sucrose reduced normal output of (14)CO(2) by whole blood. This also is probably due to (14)C-substrate dilution. It appears that 10% sucrose is potentially the most useful osmotic agent for radiometric techniques since, although bacterial (14)CO(2) production is lowered, blood (14)CO(2) is lowered also.     

Effect of Mechanical Loading on Ventilatory Response to CO2 and CO2 Excretion

The ventilatory response to CO₂ (S) and respiratory exchange ratio have been measured in 10 healthy subjects breathing naturally and through added resistive loads. The changes in these values produced by the added loads were shown to be correlated with the unloaded CO₂ responsiveness. The results indicated that poorly responsive individuals had a greater depression of ventilatory response to CO₂ and were more liable to retain CO₂.These observations raise the possibility that the constitutional CO₂ responsiveness of an individual influences the alveolar ventilation achieved in the presence of airways obstruction. The propensity to develop respiratory failure may thus be conditioned by the premorbid CO₂ responsiveness.     

The Effect of Citrulline/Malate on Blood Lactate Levels in Intensive Exercise

The purpose of this study was to examine the effects of Citrulline/Malate supplementation with intensive training on blood lactate level in active handball players. The athletes were subjected to intense training for 4 weeks, 4 days a week, mainly pre-season strength and technique training. In this training period, stimol group (n = 11) athletes were given stimol 3 times a day as 1 g for breakfast, 1 g for lunch, and 1 g for dinner while the placebo group (n = 11) athletes were given only placebo in the same dosage and the same color at the same time. Blood lactate levels in athletes were measured 4 times, prior to and after a 1-month program as follows: rest (R), end effort (EE), recuperation 5 min (R5 m), and recuperation 20 min (R20 m). Blood lactate levels were compared both as intra-group and between the groups. In intra-group comparison, no change was observed in blood lactate levels in placebo group while a significant difference was found in the levels of stimol group as p < 0.05 with a 49.8% decrease in blood lactate level. In the measurements between groups, in the post-test measurements made after the training period, significant differences as p < 0.05 were found with a 60.7% decrease in blood lactate level EE. Considerable decline was seen especially immediately after exercise in blood lactate levels of the athletes being given stimol supplement. In this case, we can say that Citrulline/Malate supplementation may contribute positively to the performance of athletes and may help postpone fatigue at excessive or prolonged activity.     

回春医疗保健操运动对老年2 型糖尿病患者血糖和血脂水平的影响

目的：探讨规律性回春医疗保健操运动对2 型糖尿病老年患者血糖、血脂水平的影响。方法：选择28例老年2 型糖尿病患者 为研究对象,并将其随机分为运动干预组和对照组。运动干预组在前期药物治疗和饮食控制不变的情况下,采用为期12 周回春 医疗保健操进行运动干预,对照组仅给予药物治疗和饮食控制,而不进行运动干预,监测和比较两组患者实验前后血糖、血脂等 指标的变化。结果：运动干预组患者接受12 周回春医疗保健操干预后,受试者空腹血糖、胆固醇、低密度脂蛋白水平均较运动干 预前显著下降,差异均具有统计学意义(P<0.05)。结论：长期的规律性回春医疗保健操运动可有效降低老年2 型糖尿病患者血糖、 血脂水平,且安全易操作,可作为老年2 型糖尿病的临床辅助疗法。