Effect of Maximal Apnoea Easy-Going and Struggle Phases on Subarachnoid Width and Pial Artery Pulsation in Elite Breath-Hold Divers

Purpose

The aim of the study was to assess changes in subarachnoid space width (sas-TQ), the marker of intracranial pressure (ICP), pial artery pulsation (cc-TQ) and cardiac contribution to blood pressure (BP), cerebral blood flow velocity (CBFV) and cc-TQ oscillations throughout the maximal breath hold in elite apnoea divers. Non-invasive assessment of sas-TQ and cc-TQ became possible due to recently developed method based on infrared radiation, called near-infrared transillumination/backscattering sounding (NIR-T/BSS).

Methods

The experimental group consisted of seven breath-hold divers (six men). During testing, each participant performed a single maximal end-inspiratory breath hold. Apnoea consisted of the easy-going and struggle phases (characterised by involuntary breathing movements (IBMs)). Heart rate (HR) was determined using a standard ECG. BP was assessed using the photoplethysmography method. SaO₂ was monitored continuously with pulse oximetry. A pneumatic chest belt was used to register thoracic and abdominal movements. Cerebral blood flow velocity (CBFV) was estimated by a 2-MHz transcranial Doppler ultrasonic probe. sas-TQ and cc-TQ were measured using NIR-T/BSS. Wavelet transform analysis was performed to assess cardiac contribution to BP, CBFV and cc-TQ oscillations.

Results

Mean BP and CBFV increased compared to baseline at the end of the easy phase and were further augmented by IBMs. cc-TQ increased compared to baseline at the end of the easy phase and remained stable during the IBMs. HR did not change significantly throughout the apnoea, although a trend toward a decrease during the easy phase and recovery during the IBMs was visible. Amplitudes of BP, CBFV and cc-TQ were augmented. sas-TQ and SaO₂ decreased at the easy phase of apnoea and further decreased during the IBMs.

Conclusions

Apnoea increases intracranial pressure and pial artery pulsation. Pial artery pulsation seems to be stabilised by the IBMs. Cardiac contribution to BP, CBFV and cc-TQ oscillations does not change throughout the apnoea.     

The Influence of Tobacco Smoking on the Relationship between Pressure and Flow in the Middle Cerebral Artery in Humans

Background

Cigarette smoking is associated with an increased risk of stroke but the mechanism is unclear. The study examined whether acute and chronic cigarette smoking alters the dynamic relationship between blood pressure and cerebral blood flow. We hypothesised that acute and chronic smoking would result in a cerebral circulation that was less capable of buffering against dynamic fluctuations in blood pressure. Further, these changes would be accompanied by a reduction in baroreflex sensitivity, which is reduced after smoking (acute smoking).

Methods

We recruited 17 non-smokers and 15 habitual smokers (13 ± 5 pack years). Continuous measurements of mean cerebral blood flow velocity (transcranial Doppler ultrasound), blood pressure (finger photoplethysmography) and heart rate enabled transfer function analysis of the dynamic relationship between pressure and flow (gain, normalised gain, phase and coherence) and baroreflex sensitivity during supine rest before and after smoking a single cigarette (acute smoking).

Results

There were no between-group differences in gain, phase or coherence before acute smoking. However, both groups showed a reduction in gain and coherence, associated with a reduction in baroreflex sensitivity, and increase in phase after acute smoking.

Conclusions

Contrary to our hypothesis, these findings suggest that in the face of a reduction in baroreflex sensitivity acute smoking may potentially improve the ability of the cerebral circulation to buffer against changes in blood pressure. However, chronic smoking did not alter the dynamic relationship between blood pressure and cerebral blood flow velocity. These results have implications on understanding mechanisms for attenuating stroke risk.     

Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects

Introduction

Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS) that allows for the non-invasive measurement of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) in humans, we assessed the influence of sympathetic activation on the cardiac and respiratory contribution to blood pressure (BP) cc-TQ oscillations in healthy subjects.

Methods

The pial artery and subarachnoid width response to handgrip (HGT) and cold test (CT) were studied in 20 healthy subjects. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV) was measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat-to-beat mean BP were recorded using a continuous finger-pulse photoplethysmography; respiratory rate (RR), minute ventilation (MV), end-tidal CO₂ (EtCO2) and end-tidal O₂ (EtO2) were measured using a metabolic and spirometry module of the medical monitoring system. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations.

Results

HGT evoked an increase in BP (+15.9%; P<0.001), HR (14.7; P<0.001), SaO₂ (+0.5; P<0.001) EtO₂ (+2.1; P<0.05) RR (+9.2%; P = 0.05) and MV (+15.5%; P<0.001), while sas-TQ was diminished (-8.12%; P<0.001), and a clear trend toward cc-TQ decline was observed (-11.0%; NS). CBFV (+2.9%; NS) and EtCO₂ (-0.7; NS) did not change during HGT. CT evoked an increase in BP (+7.4%; P<0.001), sas-TQ (+3.5%; P<0.05) and SaO₂(+0.3%; P<0.05). HR (+2.3%; NS), CBFV (+2.0%; NS), EtO₂ (-0.7%; NS) and EtCO₂ (+0.9%; NS) remained unchanged. A trend toward decreased cc-TQ was observed (-5.1%; NS). The sas-TQ response was biphasic with elevation during the first 40 seconds (+8.8% vs. baseline; P<0.001) and subsequent decline (+4.1% vs. baseline; P<0.05). No change with respect to wavelet coherence and wavelet phase coherence was found between the BP and cc-TQ oscillations.

Conclusions

Short sympathetic activation does not affect the cardiac and respiratory contribution to the relationship between BP—cc-TQ oscillations. HGT and CT display divergent effects on the width of the subarachnoid space, an indirect marker of changes in intracranial pressure.     

Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures,Infusions and Blood Sampling in a Conscious Rat Model

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat during the study while continuously monitoring pressures, infusing fluids and drugs (antibiotics, vasopressors) and performing blood sampling.     

Evaluation of Flow Velocity in Unilateral Middle Cerebral Artery Stenosis by Transcranial Doppler

To determine the optimal velocity values in diagnosing unilateral middle cerebral artery (MCA) stenosis by Transcranial Doppler (TCD), and improve the diagnostic accuracy using magnetic resonance angiography (MRA), a total of 302 unilateral MCA stenosis patients undergoing TCD also consented to a MRA of the intracranial arteries. The peak systolic velocity (PSV) and each MCA spectrum for each patient were recorded. Using the MRA to confirm, the degree of middle cerebral artery stenosis was categorized into four groups: normal (normal caliber and signal), mild (<50 %), moderate (50–69 %), severe (70–99 %, or no flow detected). The velocity difference among these four groups was significant (P < 0.001). The optimal PSV values for normal and stenosis were 160 cm/s. For mild and moderate were 200 cm/s, for moderate and severe were 280 cm/s. Using PSV as the diagnostic criteria, the Kappa number was >0.668. The optimal PSV differential value for mild and moderate was 70 cm/s, for moderate and severe at 120 cm/s. Optimal combined criteria for moderate stenosis were PSV >200 cm/s and PSV differential value >70 cm/s (specificity 87.2 %), for severe stenosis were PSV >280 cm/s and PSV differential value >120 cm/s (sensibility 81.6 %). Transcranial Doppler distinguishes normal and MCA stenosis with a reduced lumen diameter of less than 50 %. Using the PSV criteria, TCD has a high coincidence rate with MRA in the diagnosis of MCA stenosis. Combined PSV differential value and the abnormal spectrum may improve the accuracy of TCD in diagnosing moderate or severe stenosis.     

The Acute and Chronic Effects of Monosodium l-Glutamate on Serum Iron and Total Iron-Binding Capacity in the Jugular Artery and Vein of Pigs

We analyzed the effects of acute and chronic oral administration of monosodium l-glutamate (MSG) on serum iron (Fe) levels and total iron-binding capacity (TIBC) in piglets. In the first experiment, 12 piglets were randomly assigned to two groups: one fed a standard diet (SD) and the other fed an SD containing MSG (10 g/kg). On day 30, serum, liver, kidney, and spleen samples were collected to determine the Fe levels. In the second experiment, six pigs were surgically fitted with a catheter in the jugular artery and vein to investigate the dynamic changes of serum Fe and TIBC. Blood samples were taken from each pig via the catheter every 30 min, for a period of 4 h. The results show that MSG increases Fe levels in the spleen (P?<?0.05) and in serum obtained from the jugular artery (P?<?0.01). In addition, TIBC in serum obtained from the jugular artery demonstrated an increasing trend in pigs fed the MSG diet; however, this trend was not observed in the jugular vein. In conclusion, MSG increases Fe retention by enhancing TIBC in serum.     

Elevation of Platelet Activating Factor,Inflammatory Cytokines,and Coagulation Factors in the Internal Jugular Vein of Patients with Subarachnoid Hemorrhage

The aim of the present study was to examine the changes of inflammatory and coagulation factors in blood of the internal jugular vein, not of peripheral vein, in patients with subarachnoid hemorrhage (SAH). The results show that while interleukin-6 (IL-6) and platelet activating factor (PAF) concentrations increased within first 4 days after SAH and remained elevated up to 14 days, interleukin-1 (IL-1 showed a transient increase between 5–9 days after SAH and tumor necrosis factor- (TNF-) remained unchanged. Also different coagulation factors were increased between 5–9 days after SAH. Moreover, patients with delayed ischemic neurological deficits (DIND) displayed the highest levels of PAF and the coagulation factors, von Willebrand factor (vWF) and thrombin-antithrombin III complex (TAT). These results suggest that elevation of PAF and other inflammatory cytokines following SAH may cause the hypercoagulation state that is associated with cerebral vasospasm and internal jugular vein may be more adequate vessel for sampling blood to examine these factors.     

Combined Hepatic Vein, Umbilicoportal Vein, and Superior Mesenteric Artery Catheterization in Portal Hypertension: Estimation of the Portal Fraction of Total Hepatic Blood Flow in Cirrhotic Patients

Hemodynamic data were obtained in 13 cirrhotic patients with severe portal hypertension, undergoing combined hepatic vein, umbilicoportal vein, and superior mesenteric artery catheterization. The relative clearance of indocyanine green, the portohepatic gradient (difference between the free portal venous pressure and the free hepatic venous pressure), and the estimated hepatic blood flow were measured. The portal fraction (PF) of total hepatic blood flow was calculated in all patients using indicator dilution curves obtained from the portal bifurcation, a right hepatic vein, and when possible a left hepatic vein (six cases) after injection of ⁵¹Cr-labeled red blood cells (⁵¹Cr RBC) into the superior mesenteric artery. Flows were overestimated because of loss of indicator through spontaneous portosystemic shunts; however, the ratio between hepatic and portal indicator dilution curves can be used to calculate the portal fraction of total hepatic blood flow since no extrahepatic shunts existed after the bifurcation of the portal vein (as shown on portography). In 10 patients, 15 series of curves were calculable and the PF varied between 30.1 and 100% (mean ± SE: 71.1 ± 6.2%). In the three other patients, only delayed activity from recirculation was detected from portal and hepatic vein samples and PF was 0%; in these three cases, portography and arteriography revealed spontaneous portacaval shunting with reverse and/or stagnant circulation in the portal vein. In the 13 patients, no correlation existed between PF and the relative clearance of indocyanine green or the portohepatic gradient, parameters generally used as indices of severity in cirrhosis. In 10 patients, no correlation was found between PF and the estimated hepatic blood flow.     

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.     

Cerebral Oxidative Metabolism and Blood Flow During Acute Hypoglycemia and Recovery in Unanesthetized Rats

Abstract: Progressive neurological depression leading to coma was produced in unanesthetized rats at a constant level of hypoglycemia induced by insulin. High-energy phosphate concentrations in brain remained normal during hypoglycemic lethargy, but ATP declined by 6% during stupor and by 40% during coma that was characterized by an isoelectric EEG. Cerebral blood flow (CBF) remained normal during hypoglycemia whereas the cerebral metabolic rates for oxygen (CMRo₂) and glucose (CMR_glucose) decreased by 45 and 73%, respectively, indicating oxidation of nonglucose fuels. A plot of CMRo₂ and CMR_glucose versus plasma glucose indicated increasing oxidation of alternate substrates (elevated CMRo²/CMR_glucose) at plasma glucose concentrations below 2.5 mm . The cerebral uptake of β-hydroxybutyrate increased during hypoglycemic stupor and its complete oxidation could account for the CMRo₂ in excess of glucose utilization. Brain ammonia, a byproduct of amino acid metabolism, reached a level during hypoglycemic coma sufficient to produce coma in normoglycemic animals. The rate and degree of recovery after glucose administration depended on the duration of hypoglycemia and the pretreatment neurological state of the animal. Following 10 min of glucose infusion, ATP levels that were modestly depressed in stuporous rats recovered fully, paralleling the animals' apparently full neurological recovery. Rats that had been in hypoglycemic coma for 1 min or less fully recovered high-energy phosphate concentrations in brain. However, when normalization of plasma glucose was delayed for more than 1 min of coma, the CMRo₂ remained depressed, CBF decreased to 40% of control, and high-energy substrates failed to normalize. In keeping with the depression of oxidative metabolism and blood flow, neurological function and the EEG remained abnormal even after 1 h of glucose infusion. The findings suggest that irreversible brain injury may develop within the first minutes of hypoglycemic coma.     

调任通督针刺法联合感觉统合训练对注意缺陷多动障碍患儿注意力和脑动脉血流速度的影响

摘要 目的：观察感觉统合训练联合调任通督针刺法对注意缺陷多动障碍（ADHD）患儿注意力和脑动脉血流速度的影响。方法：纳入东莞市中医院2020年1月到2021年1月期间收治的ADHD患儿100例,入组患儿按门诊号单双数分为对照组（单数,感觉统合训练）和研究组（双数,调任通督针刺法联合感觉统合训练）,各为50例,两组患儿均干预3个月。观察并对比两组疗效、中医证候总积分、注意力、脑动脉血流速度、Conners父母评症状量表（PSQ）、联合型瑞文测验 (CRT) 评分。结果：研究组的临床总有效率明显高于对照组（P<0.05）。干预3个月后,两组注意力情况：错误数、漏报数较干预前减少,反应时间较干预前缩短,且研究组的变化程度大于对照组（P<0.05）。研究组患儿干预3个月后双侧中动脉（MCA）、前动脉（ACA）、后动脉（PCA）的血流速度均较干预前增快,且高于同时期的对照组患儿（P＜0.05）。干预3个月后,两组PSQ评分、中医证候总积分下降,CRT评分升高,且研究组的变化程度大于对照组（P<0.05）。结论：调任通督针刺法联合感觉统合训练可有效改善ADHD患儿注意力,促进临床症状改善,调节脑血流速度,临床应用价值较好。     

不同剂量阿托伐他汀联合依达拉奉对急性脑梗死患者血脂、炎症因子和脑血流指标的影响

摘要 目的：探讨依达拉奉分别联合不同剂量的阿托伐他汀对急性脑梗死（ACI）患者血脂、炎症因子和脑血流指标的影响。方法：纳入2018年3月~2020年1月期间我院收治的81例ACI患者,采用随机数字表法分为低剂量组（依达拉奉联合10 mg/d阿托伐他汀治疗）、中剂量组（依达拉奉联合20 mg/d阿托伐他汀治疗）和高剂量组（依达拉奉联合40 mg/d阿托伐他汀治疗）,每组各27例。对比三组疗效、血脂、炎症因子、脑血流指标、相关量表评分及不良反应。结果：治疗14 d后,高剂量组、中剂量组总有效率高于低剂量组,且高剂量组高于中剂量组（P<0.05）。治疗14 d后,高剂量组、中剂量组美国国立卫生研究院卒中量表（NIHSS）、改良Rankin 量表（mRS）评分和总胆固醇 (TC ) 、三酰甘油 (TG )、低密度脂蛋白胆固醇 (LDL-C )、超敏C反应蛋白（hs-CRP）、白介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）低于低剂量组,且高剂量组低于中剂量组（P<0.05）。治疗14 d后,高剂量组、中剂量组高密度脂蛋白胆固醇 (HDL-C )高于低剂量组,且高剂量组高于中剂量组（P<0.05）。治疗14 d后,三组平均血流速度较治疗前增加,外周阻力较治疗前降低（P<0.05）,但三组间平均血流速度和外周阻力比较差异无统计学意义（P>0.05）。三组不良反应发生率组间对比差异无统计学意义（P>0.05）。结论：40 mg/d阿托伐他汀联合依达拉奉治疗ACI患者,可更加有效控制疾病进展,改善机体血脂、炎症因子,较为安全可靠,但有关脑血流的改变可能与阿托伐他汀剂量无关。     

Relationships between Cerebral Blood Flow Dynamics and Bioelectric Activity of the Human Brain in Experimental Acute Hypoxia

The relationships between the parameters of oxygen content in the body (hemoglobin saturation with oxygen and trancutaneous oxygen tension), central hemodynamics (cardiac output), and cerebral hemodynamics (cerebral blood flow rate) were studied during a hypoxic test (inhalation of an oxygen–nitrogen mixture containing 8% oxygen for 15 min). Special attention was paid to the relationships between the dynamics of cerebral blood flow and cerebral bioelectric activity measured by EEG parameters. It was demonstrated that the trancutaneous oxygen tension decreased to a greater extent than the hemoglobin saturation with oxygen and the cerebral blood flow increased to a greater extent than the cardiac output. The increase in cerebral blood flow and the increase in the indices and power of and EEG waves in the course of hypoxia were strongly positively correlated with each other in most subjects. However, if these parameters were considered in the series of subjects, the degree of the increase in the indices and power of and waves in different subjects was negatively correlated with the increase in the cerebral blood flow. The results are explained in terms of redistribution of blood flow in the body to provide a better oxygen supply to the brain and optimization of the ratios between the cerebral oxygen consumption and the functional load on the system of oxygen supply.     

Quantification of Blood Flow in Internal Cerebral Artery by Optical Flow Method on Digital Subtraction Angiography in Comparison with Time-Of-Flight Magnetic Resonance Angiography

Objective

This study compared data on the blood flow velocity in the internal carotid artery, which was obtained using the optical flow method (OFM) with digital subtraction angiography (DSA) and the time-of-flight (TOF) technique using magnetic resonance angiography (MRA).

Materials and Methods

Images were obtained from 12 cerebrovascular patients who underwent both brain DSA and MRA imaging. The OFM was applied on the DSA images to determine the average blood flow velocity. The calculated results were compared with the values obtained from the TOF-MRA data. A linear fit was performed on the data and Bland-Altman plots were analyzed.

Results

The blood flow velocity was closely associated with vascular diseases. Color-coding of the OFM measurements were superimposed on to the DSA images, which quantitatively illustrated the relative flow in the vessels. The average blood flow velocity was calculated using OFM and DSA, which demonstrated a high correlation with the MRA measurements in the anterior-posterior (AP) view (R = 0.71). In contrast, the average blood flow velocity was low in the lateral view (R = 0.28). The consistency between the high and low blood velocity in the AP view was better compared to the lateral view. The blood flow velocity distribution in the AP view was statistically closer to the MRA measurement compared to the lateral view.

Conclusions

This study evaluated the correlation of blood flow measured using DSA and TOF-MRA in a small heterogeneous group of patients with cerebrovascular lesions. OFM with DSA imaging reveals hemodynamic information and TOF-MRA.     

A Sphincter in the Pulmonary Artery of the Frog Rana temporaria and Its Influence on Blood Flow in Skin and Lungs

A sphincter is described in the a. pulmonalis in the frog Rana temporaria. The sphincter begins abruptly where the pulmonary artery branches off from the a. pulmo-cutanea. It is constricted by vagal stimulation and acetylcholine. It also contracts actively when the lungs are artificially collapsed and opens when the lungs are inflated. It is suggested that previously reported fibers in the vagus nerve, which come from stretch receptors in the lungs, act as the afferent reflex arch. When the pulmonary artery constricts, the cutaneous artery and vein are distended by increased pressure which contributes to increased cutaneous flow. The sphincter therefore seems to play an important role in the adjustment of circulation to exclusive cutaneous respiration as for instance in submerged, wintering frogs. It is suggested that the decrease of pulmonary flow in such situations causes increased mixing in the heart and, perhaps, complete break-down of the double circulation. In frogs with exclusive skin respiration this would seem to be a functional necessity. Sphincters of similar location in turtles seem to be homologous with the one in Rana.     

Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in peripheral arterial bypass surgery as well as in arteriovenous fistulas.^1-5 The experimental procedure of vein graft interposition in the common carotid artery by using the cuff-technique has been applied in several research projects to examine the aetiology of neointimal hyperplasia and therapeutic options to address it. ^6-8 The cuff prevents vessel anastomotic remodeling and induces turbulence within the graft and thereby the development of neointimal hyperplasia.Using the superior caval vein graft is an established small-animal model for venous arterialization experiment.^9-11 This current protocol refers to an established jugular vein graft interposition technique first described by Zou et al., ⁹ as well as others.^12-14 Nevertheless, these cited small animal protocols are complicated.To simplify the procedure and to minimize the number of experimental animals needed, a detailed operation protocol by video training is presented. This video should help the novice surgeon to learn both the cuff-technique and the vein graft interposition. Hereby, the right external jugular vein was grafted in cuff-technique in the common carotid artery of 21 female Sprague Dawley rats categorized in three equal groups that were sacrificed on day 21, 42 and 84, respectively. Notably, no donor animals were needed, because auto-transplantations were performed. The survival rate was 100 % at the time point of sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated animals and 82 % for the remaining 11 animals. The blood flow at the time of sacrifice was 8±3 ml/min. In conclusion, this surgical protocol considerably simplifies, optimizes and standardizes this complicated procedure. It gives novice surgeons easy, step-by-step instruction, explaining possible pitfalls, thereby helping them to gain expertise fast and avoid useless sacrifice of experimental animals.     

Effect of Gravity on Blood Distribution and Flow in Large Vessels of Healthy Humans

Ultrasound imaging of vessels and flow Doppler ultrasonography were used to study the hemodynamic responses of large arteries and veins to orthostasis in 230 healthy human subjects of both sexes. The arterial system was shown to respond to orthostasis by differentially reducing the blood flow capacity and velocity, especially the blood supply to the lower extremities. During one-leg upright standing, the blood flow in the arterial bed of the weight-bearing leg was redistributed in favor of antigravity calf muscles. No blood flow redistribution was observed in the vertically oriented non-weight-bearing leg. A single voluntary contraction of the triceps surae muscles caused a transient increase in the volume blood flow in the femoral vein (by 2.5- to 5.0-fold in the recumbent position of the body and by 4- to 10-fold in the upright position).     

Pentoxifylline Effects on Nerve Conduction Velocity and Blood Flow in Diabetic Rats

Pentoxifylline has several actions that improve blood rheology and tissue perfusion and may therefore potentially be applicable to diabetic neuropathy. The aims of this study were to ascertain whether 2 weeks of treatment with pentoxifylline could correct nerve conduction velocity and blood flow deficits in 6-week streptozotocin-diabetic rats and to examine whether the effects were blocked by co-treatment with the cyclooxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, N^G-nitro-ʟ-arginine. Diabetic deficits in sciatic motor and saphenous sensory nerve conduction velocity were 56.5% and 69.8% corrected, respectively, with pentoxifylline treatment. Sciatic endoneurial blood flow was approximately halved by diabetes and this deficit was 50.4% corrected by pentoxifylline. Flurbiprofen co-treatment markedly attenuated these actions of pentoxifylline on nerve conduction and blood flow whereas N^G-nitro-ʟ-arginine was without effect. Thus, pentoxifylline treatment confers neurovascular benefits in experimental diabetic neuropathy, which are linked at least in part to cyclooxygenasemediated metabolism.     

Numerical Models of Auto-regulation and Blood Flow in the Cerebral Circulation

A two-dimensional time-dependent computational fluid dynamics model of the Circle of Willis has been developed. To simulate, not only the peripheral resistance of the cerebrovascular tree but also its auto-regulation function, a new "active" boundary condition has been defined and developed using control theory to provide a model of the feedback mechanism. The model was then used to simulate different common abnormalities of the Circle of Willis while a pressure drop, simulating a rapid compression of the right internal carotid artery, was imposed. Test results using a simple tube compared excellently with experiment. The total time-dependent flux for each efferent artery was tabulated and showed the important relationship between geometrical variations in the Circle of Willis and the auto-regulation of blood flow by vascular vaso-dilation and contraction. From this study, it was found that the worst case seemed to be that of a missing or dysfunctional right A1 segment of the anterior cerebral artery. The use of valid physiological models of the peripheral resistance allows for more realistic models of the blood flow in the Circle whilst allowing an easy extension to 3D patient specific simulations.     

The Effect of Adding CO2 to Hypoxic Inspired Gas on Cerebral Blood Flow Velocity and Breathing during Incremental Exercise

Hypoxia increases the ventilatory response to exercise, which leads to hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood flow (CBF). We studied the effects of adding CO₂ to a hypoxic inspired gas on CBF during heavy exercise in an altitude naïve population. We hypothesized that augmented inspired CO₂ and hypoxia would exert synergistic effects on increasing CBF during exercise, which would improve exercise capacity compared to hypocapnic hypoxia. We also examined the responsiveness of CO₂ and O₂ chemoreception on the regulation ventilation (E) during incremental exercise. We measured middle cerebral artery velocity (MCAv; index of CBF), E, end-tidal PCO₂, respiratory compensation threshold (RC) and ventilatory response to exercise (E slope) in ten healthy men during incremental cycling to exhaustion in normoxia and hypoxia (FIO₂ = 0.10) with and without augmenting the fraction of inspired CO₂ (FICO₂). During exercise in normoxia, augmenting FICO₂ elevated MCAv throughout exercise and lowered both RC onset andE slope below RC (P<0.05). In hypoxia, MCAv and E slope below RC during exercise were elevated, while the onset of RC occurred at lower exercise intensity (P<0.05). Augmenting FICO₂ in hypoxia increased E at RC (P<0.05) but no difference was observed in RC onset, MCAv, or E slope below RC (P>0.05). The E slope above RC was unchanged with either hypoxia or augmented FICO₂ (P>0.05). We found augmenting FICO₂ increased CBF during sub-maximal exercise in normoxia, but not in hypoxia, indicating that the ‘normal’ cerebrovascular response to hypercapnia is blunted during exercise in hypoxia, possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may explain the lack of improvement of exercise capacity in hypoxia with augmented CO₂. Our data further indicate that, during exercise below RC, chemoreception is responsive, while above RC the ventilatory response to CO₂ is blunted.