Effect of preceding exercise on cerebral and splanchnic vascular responses to mental task

Background

To investigate the effect of preceding acute exercise on the peripheral vascular response to a mental task, we measured splanchnic and cerebral blood flow responses to performing a mental task after exercise and resting.

Methods

In the exercise trial, 11 males exercised for 30 min on a cycle ergometer with a workload set at 70% of the age-predicted maximal heart rate for each individual. After a 15-min recovery period, the subjects rested for 5 min for pre-task baseline measurement and then performed mental arithmetic for 5 min followed by 5 min of post-task measurement. In the resting trial, they rested for 45 min and pre-task baseline data was obtained for 5 min. Then mental arithmetic was performed for 5 min followed by post-task measurement. We measured the mean blood velocity in the middle cerebral artery and superior mesenteric artery and the mean arterial pressure.

Results

Mean arterial pressure and mean blood velocity in the middle cerebral artery were significantly higher than the baseline during mental arithmetic in both exercise and resting trials. Mean blood velocity in the middle cerebral artery during mental arithmetic was greater in the control trial than the exercise trial. Mean blood velocity in the superior mesenteric artery showed no significant change during mental arithmetic from baseline in both trials.

Conclusion

These results suggest that acute exercise can moderate the increase in cerebral blood flow induced by a mental task.     

Evaluation of the Combined Application of Ultrasound Imaging Techniques for Middle Cerebral Artery Stent Surveillance and Follow-Up Study

Objective

In recent years, cerebral artery stenting has become an effective method for the treatment of cerebral artery stenosis. However, methods for assessing efficacy and techniques for follow-up imaging still need to be developed. This study was designed to evaluate the application of transcranial color-coded sonography (TCCS) in assessing stenting of middle cerebral artery (MCA) stenosis. And, two new imaging techniques (vascular enhancement technology (VET) and 3-dimensional (3D) imaging) were tried out and evaluated.

Method

We enrolled 43 patients with cerebral artery stenosis for vascular stent implantation. All patients were examined by ultrasonography and confirmed through digital subtraction angiography. The stenosis was imaged and blood flow parameters were analyzed before and after the procedure using TCCS. VET and 3D imaging model were used in part of the patients. Important postoperative hemodynamic changes were noted.

Results

1) Adequate stent image was present in 41 out of 43 patients as detected by postoperative 2-dimensional imaging. Images lacking clarity were obtained in 2 patients. 2) The perioperative and postoperative (one week follow-up) instantaneous blood flow velocity at the site of stenosis was significantly decreased (P<0.05) when compared with preoperative levels. Differences between postoperative (one week follow-up) and preoperative blood flow velocity were significant (P<0.05). Differences in blood flow velocity at long-term follow-up (six months and two years) compared to one-week values were not statistically significant (P>0.05). 3) VET imaging visualizes the MCA lumen and stent morphology clearly. 3D ultrasound can be used for imaging of the stent shape as well as its inner surface.

Conclusion

TCCD can be considered a quick and effective clinical detection method to evaluate the intracranial arterial hemodynamics changes before and after stenting treatment for MCA stenosis. New imaging technologies 3D and VET can achieve additional image information.     

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.     

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.     

Disease activity and cognition in rheumatoid arthritis: an open label pilot study

Introduction

We hypothesised that fatigue in rheumatoid arthritis (RA) is related to TNF-alpha induced dysregulation of cerebral blood flow. Our objectives were to assess fatigue, cognitive function and cerebral blood flow before and after initiation of anti-TNF treatment.

Methods

In a pilot study, 15 patients initiating treatment with adalimumab were assessed for fatigue using a visual analogue scale (FACIT-F), cognitive function using a panel of psychometric tests and regional cerebral blood flow using MR perfusion imaging.

Results

Patients improved clinically after anti-TNF therapy in terms of DAS28 and FACIT-F. Furthermore significant improvements were documented in full scale, verbal and performance IQ following therapy. There was a non-significant trend towards reduced cerebral perfusion in both grey and white matter, and fatigue at 3 months correlated with cerebral blood flow in white (p = 0.014) and grey (p = 0.005) matter.

Conclusions

We demonstrate for the first time a significant improvement in cognitive function following effective treatment of RA. Although we observed minor reductions in cerebral blood flow, and a correlation between cerebral blood flow and fatigue, a larger, controlled study would be required to affirm a causal relationship.     

Migraine with Aura Is Associated with an Incomplete Circle of Willis: Results of a Prospective Observational Study

Objective

To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion.

Methods

Migraine with aura, migraine without aura, and control subjects were prospectively enrolled in a 1∶1∶1 ratio. Magnetic resonance angiography was performed to examine circle of Willis anatomy and arterial spin labeled perfusion magnetic resonance imaging to measure cerebral blood flow. A standardized template rating system was used to categorize circle of Willis variants. The primary pre-specified outcome measure was the frequency of an incomplete circle of Willis. The association between circle of Willis variations and cerebral blood flow was also analyzed.

Results

170 subjects were enrolled (56 migraine with aura, 61 migraine without aura, 53 controls). An incomplete circle of Willis was significantly more common in the migraine with aura compared to control group (73% vs. 51%, p = 0.02), with a similar trend for the migraine without aura group (67% vs. 51%, p = 0.08). Using a quantitative score of the burden of circle of Willis variants, migraine with aura subjects had a higher burden of variants than controls (p = 0.02). Compared to those with a complete circle, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow (p = 0.05). Specific posterior cerebral artery variants were associated with greater asymmetries of blood flow in the posterior cerebral artery territory.

Conclusions

An incomplete circle of Willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.     

Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma

Background

The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle.

Methods

Sheep previously sensitized to house dust mite (HDM) were challenged with HDM aerosols to induce early asthmatic responses. At the maximal responses (characterised by an increase in lung resistance), the sheep were either not treated or treated with one of the following; nebulized S-1226 (perflubron + 12% CO₂), nebulized perflubron + medical air, 12% CO₂, salbutamol or medical air. Lung resistance was monitored for up to 20 minutes after cessation of treatment.In additional naïve sheep, a segmental bronchus was pre-contracted with methacholine (MCh) and treated with nebulized S-1226 administered via a bronchoscope catheter. Subsequent bronchodilatation was monitored by real time digital video recording.

Results

Treatment with S-1226 for 2 minutes following HDM challenge resulted in a more rapid, more profound and more prolonged decline in lung resistance compared with the other treatment interventions. Video bronchoscopy showed an immediate and complete (within 5 seconds) re-opening of MCh-constricted airways following treatment with S-1226.

Conclusions

S-1226 is a potent and rapid formulation for re-opening constricted airways. Its mechanism(s) of action are unknown. The formulation has potential as a rescue treatment for acute severe asthma.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0098-x) contains supplementary material, which is available to authorized users.     

Possible influences of exercise-intensity-dependent increases in non-cortical hemodynamic variables on NIRS-based neuroimaging analysis during cognitive tasks: Technical note

[Purpose]

Functional near-infrared spectroscopy (fNIRS) provides functional imaging of cortical activations by measuring regional oxy- and deoxy-hemoglobin (Hb) changes in the forehead during a cognitive task. There are, however, potential problems regarding NIRS signal contamination by non-cortical hemodynamic (NCH) variables such as skin blood flow, middle cerebral artery blood flow, and heart rate (HR), which are further complicated during acute exercise. It is thus necessary to determine the appropriate post-exercise timing that allows for valid NIRS assessment during a task without any increase in NCH variables. Here, we monitored post-exercise changes in NCH parameters with different intensities of exercise.

[Methods]

Fourteen healthy young participants cycled 30, 50 and 70% of their peak oxygen uptake (Vo_2peak) for 10 min per intensity, each on different days. Changes in skin blood flow velocity (SBFv), middle cerebral artery mean blood velocity (MCA V_mean) and HR were monitored before, during, and after the exercise.

[Results]

Post-exercise levels of both SBFv and HR in contrast to MCA V_mean remained high compared to basal levels and the times taken to return to baseline levels for both parameters were delayed (2-8 min after exercise), depending upon exercise intensity.

[Conclusion]

These results indicate that the delayed clearance of NCH variables of up to 8 min into the post-exercise phase may contaminate NIRS measurements, and could be a limitation of NIRS-based neuroimaging studies.     

Shared Brain Lateralization Patterns in Language and Acheulean Stone Tool Production: A Functional Transcranial Doppler Ultrasound Study

Background

The popular theory that complex tool-making and language co-evolved in the human lineage rests on the hypothesis that both skills share underlying brain processes and systems. However, language and stone tool-making have so far only been studied separately using a range of neuroimaging techniques and diverse paradigms.

Methodology/Principal Findings

We present the first-ever study of brain activation that directly compares active Acheulean tool-making and language. Using functional transcranial Doppler ultrasonography (fTCD), we measured brain blood flow lateralization patterns (hemodynamics) in subjects who performed two tasks designed to isolate the planning component of Acheulean stone tool-making and cued word generation as a language task. We show highly correlated hemodynamics in the initial 10 seconds of task execution.

Conclusions/Significance

Stone tool-making and cued word generation cause common cerebral blood flow lateralization signatures in our participants. This is consistent with a shared neural substrate for prehistoric stone tool-making and language, and is compatible with language evolution theories that posit a co-evolution of language and manual praxis. In turn, our results support the hypothesis that aspects of language might have emerged as early as 1.75 million years ago, with the start of Acheulean technology.     

Outcomes of Middle Cardiac Vein Arterialization via Internal Mammary/Thoracic Artery Anastomosis

Objective

Cardiac vein arterialization is seldom applied for treating right coronary artery disease. This study aimed to improve outcomes of cardiac vein arterialization in a porcine model using intramammary artery anastomosis.

Methods

A chronic, stenotic coronary artery model was established in 12 of 14 Chinese experimental miniature pigs of either sex, which were randomly divided into equal control (n = 6) and experimental (n = 6) groups. In experimental animals, blood flow was reconstructed in the right coronary artery using intramammary artery. Arterialization involved dissection of right internal mammary artery from bifurcation to apex of thorax followed by end-to-side anastomosis of internal mammary artery and middle cardiac vein plus posterior descending branch of right coronary artery. Intraoperative heart rate was maintained at 110 beats/min. Graft flow assessment and echocardiography were performed when blood pressure and heart rate normalized.

Results

The experimental group had significantly higher mean endocardial and epicardial blood flow postoperatively than control group (mean endocardial blood flow: 0.37 vs. 0.14 ml/(g*min), p<0.001; mean epicardial blood flow: 0.29 vs. 0.22, p = 0.014). Transmural blood flow was also higher in experimental group than in control group (0.33 vs. 0.19, p<0.001); ejection fraction increased from 0.46% at baseline to 0.51% (p = 0.0038) at 6 hours postoperatively, and mean blood flow of internal mammary artery was 44.50, perfusion index 0.73 at postoperative 6 months, 43.33 and 0.80 at 3 months.

Conclusion

Successful cardiac vein arterialization via intramammary artery in a porcine model suggests that this may be a viable method for reconstructing blood flow in chronic, severe coronary artery disease.     

Cerebral Oxygen Saturation: Graded Response to Carbon Dioxide with Isoxia and Graded Response to Oxygen with Isocapnia

Background

Monitoring cerebral saturation is increasingly seen as an aid to management of patients in the operating room and in neurocritical care. How best to manipulate cerebral saturation is not fully known. We examined cerebral saturation with graded changes in carbon dioxide tension while isoxic and with graded changes in oxygen tension while isocapnic.

Methodology/Principal Findings

The study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. Thirteen studies were undertaken in healthy adults with cerebral oximetry by near infrared spectroscopy. End-tidal gas concentrations were manipulated using a model-based prospective end-tidal targeting device. End-tidal carbon dioxide was altered ±15 mmHg from baseline in 5 mmHg increments with isoxia (clamped at 110±4 mmHg). End-tidal oxygen was changed to 300, 400, 500, 80, 60 and 50 mmHg under isocapnia (37±2 mmHg). Twelve studies were completed. The end-tidal carbon dioxide versus cerebral saturation fit a linear relationship (R² = 0.92±0.06). The end-tidal oxygen versus cerebral saturation followed log-linear behaviour and best fit a hyperbolic relationship (R² = 0.85±0.10). Cerebral saturation was maximized in isoxia at end-tidal carbon dioxide of baseline +15 mmHg (77±3 percent). Cerebral saturation was minimal in isocapnia at an end-tidal oxygen tension of 50 mmHg (61±3 percent). The cerebral saturation during normoxic hypocapnia was equivalent to normocapnic hypoxia of 60 mmHg.

Conclusions/Significance

Hypocapnia reduces cerebral saturation to an extent equivalent to moderate hypoxia.     

Effect of Isovolemic,Isothermic Hemodialysis on Cerebral Perfusion and Vascular Stiffness Using Contrast Computed Tomography and Pulse Wave Velocity

Background

Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness.

Methods

Chronic hemodialysis patients (7 male/3 female, mean age 58 years) were recruited. Cerebral blood flow and arterial pulse wave velocity were measured before and immediately after a hemodialysis session. To exclude effects of volume changes we kept ultrafiltration to a minimum, allowing no change in body weight. Isothermic conditions were maintained by using the GENIUS single-pass batch-dialysis system with a high-flux polysulfone dialyser. Cerebral blood flow was measured by contrast-enhanced computed tomography. Pulse wave velocity was measured using the SphygmoCor (AtCor Medical, USA) device by a single operator.

Results

This study shows for the first time that isovolemic, isothermic hemodialysis neither affected blood pressure or heart rate, nor total or regional cerebral perfusion. There was also no change in pulse wave velocity.

Conclusions

Mechanisms other than the dialysis procedure itself might be causative for the high incidence of ischemic strokes in this patient population. Moreover, the sole removal of uremic toxins does not lead to short-term effects on vascular stiffness, underlying the importance of volume control in this patient population.     

Caspase-3 contributes to ZO-1 and Cl-5 tight-junction disruption in rapid anoxic neurovascular unit damage

Background

Tight-junction (TJ) protein degradation is a decisive step in hypoxic blood-brain barrier (BBB) breakdown in stroke. In this study we elucidated the impact of acute cerebral ischemia on TJ protein arrangement and the role of the apoptotic effector protease caspase-3 in this context.

Methodology/Principal Findings

We used an in vitro model of the neurovascular unit and the guinea pig whole brain preparation to analyze with immunohistochemical methods the BBB properties and neurovascular integrity. In both methodological approaches we observed rapid TJ protein disruptions after 30 min of oxygen and glucose deprivation or middle cerebral artery occlusion, which were accompanied by strong caspase-3 activation in brain endothelial cells (BEC). Surprisingly only few DNA-fragmentations were detected with TUNEL stainings in BEC. Z-DEVD-fmk, an irreversible caspase-3 inhibitor, partly blocked TJ disruptions and was protective on trans-endothelial electrical resistance.

Conclusions/Significance

Our data provide evidence that caspase-3 is rapidly activated during acute cerebral ischemia predominantly without triggering DNA-fragmentation in BEC. Further we detected fast TJ protein disruptions which could be partly blocked by caspase-3 inhibition with Z-DEVD-fmk. We suggest that the basis for clinically relevant BBB breakdown in form of TJ disruptions is initiated within minutes during ischemia and that caspase-3 contributes to this process.     

Flavor-Enhanced Modulation of Cerebral Blood Flow during Gum Chewing

Background

Flavor perception, the integration of taste and odor, is a critical factor in eating behavior. It remains unclear how such sensory signals influence the human brain systems that execute the eating behavior.

Methods

We tested cerebral blood flow (CBF) in the frontal lobes bilaterally while subjects chewed three types of gum with different combinations of taste and odor: no taste/no odor gum (C-gum), sweet taste/no odor gum (T-gum), and sweet taste/lemon odor gum (TO-gum). Simultaneous recordings of transcranial Doppler ultrasound (TCD) and near infrared spectrometer (NIRS) were used to measure CBF during gum chewing in 25 healthy volunteers. Bilateral masseter muscle activity was also monitored.

Results

We found that subjects could discriminate the type of gum without prior information. Subjects rated the TO-gum as the most flavorful gum and the C-gum as the least flavorful. Analysis of masseter muscle activity indicated that masticatory motor output during gum chewing was not affected by taste and odor. The TCD/NIRS measurements revealed significantly higher hemodynamic signals when subjects chewed the TO-gum compared to when they chewed the C-gum and T-gum.

Conclusions

These data suggest that taste and odor can influence brain activation during chewing in sensory, cognitive, and motivational processes rather than in motor control.     

Impact of Intermittent Apnea on Myocardial Tissue Oxygenation—A Study Using Oxygenation-Sensitive Cardiovascular Magnetic Resonance

Background

Carbon dioxide (CO₂) is a recognized vasodilator of myocardial blood vessels that leads to changes in myocardial oxygenation through the recruitment of the coronary flow reserve. Yet, it is unknown whether changes of carbon dioxide induced by breathing maneuvers can be used to modify coronary blood flow and thus myocardial oxygenation. Oxygenation-sensitive cardiovascular magnetic resonance (CMR) using the blood oxygen level-dependent (BOLD) effect allows for non-invasive monitoring of changes of myocardial tissue oxygenation. We hypothesized that mild hypercapnia induced by long breath-holds leads to changes in myocardial oxygenation that can be detected by oxygenation-sensitive CMR.

Methods and Results

In nine anaesthetized and ventilated pigs, 60s breath-holds were induced. Left ventricular myocardial and blood pool oxygenation changes, as monitored by oxygenation-sensitive CMR using a T2*-weighted steady-state-free-precession (SSFP) sequence at 1.5T, were compared to changes of blood gas levels obtained immediately prior to and after the breath-hold. Long breath-holds resulted in an increase of paCO₂, accompanied by a decrease of paO₂ and pH. There was a significant decrease of blood pressure, while heart rate did not change. A decrease in the left ventricular blood pool oxygenation was observed, which was similar to drop in SaO₂. Oxygenation in the myocardial tissue however, was maintained throughout the period. Changes in myocardial oxygenation were strongly correlated with the change in paCO₂ during the breath-hold (r = 0.90, p = 0.010).

Conclusion

Despite a drop in blood oxygen levels, myocardial oxygenation is maintained throughout long breath-holds and is linearly correlated with the parallel increase of arterial CO₂, a known coronary vasodilator. Breathing maneuvers in combination with oxygenation-sensitive CMR may be useful as a diagnostic test for coronary artery function.     

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.     

Effect of hyperoxia and hypercapnia on tissue oxygen and perfusion response in the normal liver and kidney

Objective

Inhalation of air with altered levels of oxygen and carbon dioxide to manipulate tissue oxygenation and perfusion has both therapeutic and diagnostic value. These physiological responses can be measured non-invasively with magnetic resonance (MR) relaxation times. However, interpreting MR measurements is not straight-forward in extra-cranial organs where gas challenge studies have only begun to emerge. Inconsistent results have been reported on MR, likely because different organs respond differently. The objective of this study was to elucidate organ-specific physiological responses to gas challenge underlying MR measurements by investigating oxygenation and perfusion changes in the normal liver and kidney cortex.

Materials and Methods

Gas challenges (100% O₂, 10% CO₂, and carbogen [90% O₂+10% CO₂]) interleaved with room air was delivered to rabbits to investigate their effect on tissue oxygenation and perfusion. Real-time fiber-optic measurements of absolute oxygen and relative blood flow were made in the liver and kidney cortex.

Results

Only the liver demonstrated a vasodilatory response to CO₂. Perfusion changes to other gases were minimal in both organs. Tissue oxygenation measurements showed the liver responding only when CO₂ was present and the kidney only when O₂ was present.

Conclusion

This study reveals distinct physiological response mechanisms to gas challenge in the liver and kidney. The detailed characterization of organ-specific responses is critical to improving our understanding and interpretation of MR measurements in various body organs, and will help broaden the application of MR for non-invasive studies of gas challenges.     

Brain-derived neurotrophic factor gene Val66Met polymorphism modulates reversible cerebral vasoconstriction syndromes

Background

Reversible cerebral vasoconstriction syndrome (RCVS) could be complicated by cerebral ischemic events. Hypothetical mechanisms of RCVS involve endothelial dysfunction and sympathetic overactivity, both of which were reported to be related to brain-derived neurotrophic factor (BDNF). The study investigated the association between functional BDNF Val66Met polymorphism and RCVS.

Methods

Patients with RCVS and controls were prospectively recruited and genotyped for the BDNF Val66Met polymorphism. Magnetic resonance angiography (MRA) and transcranial color-coded Doppler sonography were employed to evaluate cerebral vasoconstriction. Genotyping results, clinical parameters, vasoconstriction scores, mean flow velocities of the middle cerebral artery (V_MCA), and Lindegaard indices were analyzed. Split-sample approach was employed to internally validate the data.

Principal Findings

Ninety Taiwanese patients with RCVS and 180 age- and gender-matched normal controls of the same ethnicity completed the study. The genotype frequencies did not differ between patients and controls. Compared to patients with Met/Met homozygosity, patients with Val allele had higher mean vasoconstriction scores of all arterial segments (1.60±0.72 vs. 0.87±0.39, p<0.001), V_MCA values (116.7±36.2 vs. 82.7±17.9 cm/s, p<0.001), and LI (2.41±0.91 vs. 1.89±0.41, p = 0.001). None of the Met/Met homozygotes, but 38.9% of the Val carriers, had V_MCA values of >120 cm/s (p<0.001). Split-sample validation by randomization, age, entry time or residence of patients demonstrated concordant findings.

Conclusions

Our findings link BDNF Val66Met polymorphism with the severity of RCVS for the first time and implicate possible pathogenic mechanisms for vasoconstriction in RCVS.     

Mast Cell Dependent Vascular Changes Associated with an Acute Response to Cold Immersion in Primary Contact Urticaria

Background

While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation.

Objective

To characterize the microcirculatory events that follow mast cell degranulation.

Methodology/Principal Findings

Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine.

Conclusions/Significance

Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.