Spontaneous Blood Research Articles

Hemorrhagic transformation and cerebral edema in acute ischemic stroke: Link to cerebral autoregulation

BackgroundHemorrhagic transformation and cerebral edema are feared complications of acute ischemic stroke but mechanisms are poorly understood and reliable early markers are lacking. Early assessment of cerebrovascular hemodynamics may advance our knowledge in both areas. We examined the relationship between dynamic cerebral autoregulation (CA) in the early hours post ischemia, and the risk of developing hemorrhagic transformation and cerebral edema at 24h post stroke MethodsWe prospectively enrolled 46 patients from our center with acute ischemic stroke in the middle cerebral artery territory. Cerebrovascular resistance index was calculated. Dynamic CA was assessed by transfer function analysis (coherence, phase and gain) of the spontaneous blood flow velocity and blood pressure oscillations. Infarct volume, hemorrhagic transformation, cerebral edema, and white matter changes were collected from computed tomography performed at presentation and 24h. ResultsAt admission, phase was lower (worse CA) in patients with hemorrhagic transformation [6.6±30 versus 45±38°; adjusted odds ratio 0.95 (95% confidence internal 0.94–0.98), p=0.023] and with cerebral edema [6.6±30 versus 45±38°, adjusted odds ratio 0.96 (0.92–0.999), p=0.044]. Progression to edema was associated with lower cerebrovascular resistance (1.4±0.2 versus 2.3±1.5mmHg/cm/s, p=0.033) and increased cerebral blood flow velocity (51±25 versus 42±17cm/s, p=0.033) at presentation. All hemodynamic differences resolved at 3months ConclusionsLess effective CA in the early hour post ischemic stroke is associated with increased risk of hemorrhagic transformation and cerebral edema, possibly reflecting breakthrough hyperperfusion and microvascular injury. Early assessment of dynamic CA could be useful in identifying individuals at risk for these complications.

A1298C Polymorphism of Fetal Methylenetetrahydrofolate Reductase (MTHFR) Gene as a Risk Factor for Spontaneous Abortion

Objective: To investigate the role of A1298C polymorphism of fetal
 methylenetetrahydrofolate reductase (MTHFR) gene in spontaneous
 abortion.
 Method: The case control study design recruited 96 subjects in Siti
 Fatimah and Pertiwi mother and child hospital, Dr. Wahidin Sudirohusodo,
 Pelamonia, Bhayangkara, Syekh Yusuf, Haji and Labuang
 Baji hospital from March to September 2014. All subjects fulfilling
 the inclusion criteria were taken tissue samples from mothers experiencing
 spontaneous abortion and blood samples from normally
 born baby. The data were analyzed using Pearson chi-square with
 significant rate of 5% (p

Blood oozing: A cause of life-threatening bleeding without overt source after transcatheter aortic valve replacement

BackgroundPost-procedure non-access site-related bleedings have a significant impact on mortality in patients treated by transcatheter aortic valve replacement (TAVR). Notwithstanding, the source of these bleedings is frequently indeterminate, with potentially serious clinical implications related to lack of diagnosis and treatment. MethodsOut of 513 TAVR performed between June 2007 and January 2016 in the Interventional Cardiology Laboratory of the Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, we identified few proven cases of concealed bleeding after TAVR due to blood oozing. ResultsWe report three cases of angiographically confirmed post-TAVR non-access bleedings related to spontaneous blood oozing, a life-threatening condition consisting of diffuse capillary hemorrhage developing from vessels not directly involved by the procedure. We hypothesize that spontaneous post-procedural blood oozing may account for a substantial proportion of non-overt, non-access site-related bleeding after TAVR. ConclusionThe possibility of post-TAVR blood oozing is largely neglected in the literature, and comprehensive categorization of non-access site bleedings in current standardized endpoints of TAVR studies is missing. Early assessment with arterial and venous contrast phase angio-MDCT scans in case of post-TAVR unexplained and persistent anemia may allow diagnosis and treatment of this subtle condition.

N1 Magnitude of Auditory Evoked Potentials and Spontaneous Functional Connectivity Between Bilateral Heschl's Gyrus Are Coupled at Interindividual Level.

N1 component of auditory evoked potentials is extensively used to investigate the propagation and processing of auditory inputs. However, the substantial interindividual variability of N1 could be a possible confounding factor when comparing different individuals or groups. Therefore, identifying the neuronal mechanism and origin of the interindividual variability of N1 is crucial in basic research and clinical applications. This study is aimed to use simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data to investigate the coupling between N1 and spontaneous functional connectivity (FC). EEG and fMRI data were simultaneously collected from a group of healthy individuals during a pure-tone listening task. Spontaneous FC was estimated from spontaneous blood oxygenation level-dependent (BOLD) signals that were isolated by regressing out task evoked BOLD signals from raw BOLD signals and then was correlated to N1 magnitude across individuals. It was observed that spontaneous FC between bilateral Heschl's gyrus was significantly and positively correlated with N1 magnitude across individuals (Spearman's R = 0.829, p < 0.001). The specificity of this observation was further confirmed by two whole-brain voxelwise analyses (voxel-mirrored homotopic connectivity analysis and seed-based connectivity analysis). These results enriched our understanding of the functional significance of the coupling between event-related brain responses and spontaneous brain connectivity, and hold the potential to increase the applicability of brain responses as a probe to the mechanism underlying pathophysiological conditions.

Frequency of Spontaneous BOLD Signal Differences between Moderate and Late Preterm Newborns and Term Newborns.

Little is known about the frequency features of spontaneous neural activity in the brains of moderate and late preterm (MLPT) newborns. We used resting-state functional magnetic resonance imaging (rs-fMRI) and the amplitude of low-frequency fluctuation (ALFF) method to investigate the frequency properties of spontaneous blood oxygen level-dependent (BOLD) signals in 26 MLPT and 35 term newborns. Two frequency bands, slow-4 (0.027-0.073Hz) and slow-5 (0.01-0.027Hz), were analyzed. Our results showed widespread differences in ALFF between the two bands; differences occurred mainly in the primary sensory and motor cortices and to a lesser extent in association cortices and subcortical areas. Compared with term newborns, MLPT newborns showed significantly altered neural activity predominantly in the primary sensory and motor cortices and in the posterior cingulate gyrus/precuneus. In addition, a significant interaction between frequency bands and groups was observed in the primary somatosensory cortex. Intriguingly, these primary sensory and motor regions have been proven to be the major cortical hubs during the neonatal period. Our results revealed the frequency of spontaneous BOLD signal differences between MLPT and term newborns, which contribute to the understanding of regional development of spontaneous brain rhythms of MLPT newborns.

Spontaneous blood pressure oscillations in mechanically ventilated patients with sepsis.

In the present hypothesis-generating study, we investigated whether spontaneous blood pressure oscillations are suppressed to lower frequencies, and whether abolished oscillations are associated with an adverse outcome in mechanically ventilated patients with sepsis. We retrospectively subjected invasive steady-state blood pressure recordings from 65 mechanically ventilated patients with sepsis to spectral analysis. Modified spectral bands were visually identified by plotting spectral power against frequency. Modified middle-frequency and low-frequency (MF' and LF') oscillations were absent in 9% and 22% of the patients, respectively. In patients in whom spontaneous blood pressure oscillations were preserved, the MF' oscillations occurred at 0.021 Hz (median, interquartile range 0.013-0.030), whereas the LF' oscillations occurred at 0.009 Hz (median, interquartile range 0.006-0.010). The absence of LF' oscillations was associated with a higher 30-day mortality [50 vs. 18%, hazard ratio, 3.6 (95% confidence interval: 1.4-9.8), P=0.01]. Spontaneous blood pressure oscillations in mechanically ventilated septic patients may be suppressed to lower frequencies than previously reported for spontaneously breathing, healthy humans. Patients in whom the resultant changes in blood pressure (MF' and LF' oscillations) are abolished may have a higher risk of an adverse outcome. This may reflect suppression of the pressor area in the brainstem with subsequent sympathetic dysfunction.

The prognostic significance of bacterial DNA in patients with decompensated cirrhosis and suspected infection.

Circulating and peritoneal fragments of microbial DNA (bactDNA) are evidence for bacterial translocation in decompensated cirrhosis and may serve as a rational approach for antibiotic therapy when infection is suspected. Prospective multicenter study to investigate whether identification of bactDNA from blood or ascitic fluid (AF) by multiplex polymerase chain reaction (PCR) is associated with increased 90-day mortality in 218 patients with cirrhosis and signs of infection. BactDNA in either compartment was detected in 134 (61%) patients, comprising 54 with bactDNA in blood and AF, 48 with AF bactDNA only, and 32 with blood bactDNA only. BactDNA was associated with spontaneous bacterial peritonitis and blood stream infections (SBP/BSI), acute-on-chronic liver failure (ACLF), encephalopathy and markers of inflammation. The prevalence of bactDNA in patients with proven SBP/BSI (36/49; 73%) was similar to that in patients with sterile ACLF (37/52; 71%). Actuarial 90-day survival was 56 ± 5% in the absence of bactDNA in both compartments and did not differ if bactDNA was detected in blood only (63 ± 9%), AF only (63 ± 7%), or in blood and AF (52 ± 7%). Predictors of 90-day mortality were SBP (HR = 3.10; 95% CI: 1.90-5.06), BSI (HR = 4.94; 95% CI: 2.71-9.02), and ACLF (HR = 2.20; 95% CI: 1.44-3.35). The detection of resistance genes in blood or AF in the absence of SBP/BSI (n = 11) was associated with poor 1-year survival (HR = 2.35; 95% CI: 1.03-5.35). BactDNA in sterile body fluids did not indicate increased mortality in cirrhotic patients with suspected infection. Using multiplex PCR for risk stratification cannot be recommended in these patients.

Disrupted Intrinsic Local Synchronization in Poststroke Aphasia.

Evidence has accumulated from the task-related and task-free (i.e., resting state) studies that alternations of intrinsic neural networks exist in poststroke aphasia (PSA) patients. However, information is lacking on the changes in the local synchronization of spontaneous functional magnetic resonance imaging blood–oxygen level-dependent fluctuations in PSA at rest.We investigated the altered intrinsic local synchronization using regional homogeneity (ReHo) on PSA (n = 17) and age- and sex-matched healthy controls (HCs) (n = 20). We examined the correlations between the abnormal ReHo values and the aphasia severity and language performance in PSA.Compared with HCs, the PSA patients exhibited decreased intrinsic local synchronization in the right lingual gyrus, the left calcarine, the left cuneus, the left superior frontal gyrus (SFG), and the left medial of SFG. The local synchronization (ReHo value) in the left medial of SFG was positively correlated with aphasia severity (r = 0.55, P = 0.027) and the naming scores of Aphasia Battery of Chinese (r = 0.66, P = 0.005). This result is consistent with the important role of this value in language processing even in the resting state.The pathogenesis of PSA may be attributed to abnormal intrinsic local synchronous in multiple brain regions.

Abstract TP363: Acute Intracerebral Hemorrhage treated in the Intensive Care Unit: Predictors of Admission, Prolonged Stay, and Functional Outcome

Introduction: Triggers for admission to the intensive care unit for patients with intracerebral hemorrhage (ICH) are unclear. Objectives: To determine the predictors of admission to the intensive care unit (ICU), factors associated with prolonged ICU stay and with long-term outcome in patients with ICH. Methods: INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of 2839 patients with spontaneous ICH (&lt;6 hours) and elevated systolic blood pressure (SBP) who were allocated to receive intensive (target SBP &lt;140mmHg) or guideline-recommended (target SBP &lt;180mmHg) blood pressure lowering treatment. Demographic, clinical and radiological indicators associated with an ICU admission, prolonged ICU stay, and poor functional outcome at 90 days were identified by multivariable logistic regression models. Results: Younger age, prior stroke, severe clinical deficit, large ICH volume, intraventricular hemorrhage (IVH), early neurological deterioration as well as need for intubation and surgical intervention were identified as predictors for an admission to the ICU. For patients who were admitted to the ICU, those with prior antihypertensive medication, severe clinical deficit, early deterioration, ICH volume ≥15 ml, lobar ICH location, IVH, who underwent intubation or surgical procedures required ICU stays longer. Older age, severe clinical deficit, early deterioration, shorter time to randomization, ICH volume ≥15 ml, and requirement for intubation and surgical intervention were associated with major disability or mortality at 90 days. Conclusions: Future plans for risk stratification of ICU admissions for ICH patients may include assessment of ICH volume, presence of IVH, NIHSS, need for intubation along with the age factor.

Non-invasive Monitoring of Dynamic Cerebrovascular Autoregulation Using Near Infrared Spectroscopy and the Finometer Photoplethysmograph.

Near infrared spectroscopy (NIRS) enables continuous monitoring of dynamic cerebrovascular autoregulation, but this methodology relies on invasive blood pressure monitoring (iABP). We evaluated the agreement between a NIRS based autoregulation index calculated from invasive blood pressure monitoring, and an entirely non-invasively derived autoregulation index from continuous non-invasive blood pressure monitoring (nABP) using the Finometer photoplethysmograph. Autoregulation was calculated as the moving correlation coefficient between iABP and rSO2 (iTOx) or nABP and rSO2 (nTOx). The blood pressure range where autoregulation is optimal was also determined for invasive (iABPOPT) and non-invasive blood pressure measurements (nABPOPT). 102 simultaneous bilateral measurements of iTOx and nTOx were performed in 19 patients (median 2 per patient, range 1-9) with different acute pathologies (sepsis, cardiac arrest, head injury, stroke). Average iTOx was 0.01±0.13 and nTOx was 0.01±0.11. The correlation between iTOx and nTOx was r=0.87, p<0.001, 95% agreement±0.12, bias=0.005. The interhemispheric asymmetry of autoregulation was similarly assessed with iTOx and nTOx (r=0.81, p<0.001). Correlation between iABPOPT and nABPOPT was r=0.47, p=0.003, 95% agreement±32.1mmHg, bias=5.8mmHg. Coherence in the low frequency spectrum between iABP and nABP was 0.86±0.08 and gain was 1.32±0.77. The results suggest that dynamic cerebrovascular autoregulation can be continuously assessed entirely non-invasively using nTOx. This allows for autoregulation assessment using spontaneous blood pressure fluctuations in conditions where iABP is not routinely monitored. The nABPOPT might deviate from iABPOPT, likely because of discordance between absolute nABP and iABP readings.

Use of intravenous insulin aspart for treatment of naturally occurring diabetic ketoacidosis in dogs.

To characterize the utility and safety of IV insulin aspart in the treatment of diabetes ketoacidosis (DKA) in dogs and to determine the times to resolution of hyperglycemia, ketonemia, and acidemia in dogs treated with IV insulin aspart. Prospective noncontrolled single arm study of dogs with DKA between February 2010 and March 2011. University teaching hospital. Six dogs with spontaneous DKA and blood glucose (BG) concentration >13.8 mmol/L (250 mg/dL), pH between 7.0 and 7.35, and blood beta-hydroxybutyrate >2.0 mmol/L were treated with an IV continuous rate infusion (CRI) of aspart insulin. The time to biochemical resolution of DKA was defined as the time interval from when the IV CRI of aspart insulin began until marked hyperglycemia (BG concentration >13.8 mmol/L [250 mg/dL]), acidemia (venous pH <7.35), and ketonemia (beta-hydroxybutyrate concentration >2.0 mmol/L) resolved. Aspart insulin was administered as an IV CRI at an initial dose of 0.09 U/kg/h. The dose was adjusted according to a previously published protocol. The median time to biochemical resolution of DKA in dogs treated with insulin aspart was 28 hours (range, 20-116 h). Mean BG concentration decreased significantly from the time IV fluid resuscitation began (32.0 mmol/L [576 mg/dL]; range, 14.9-38.9 mmol/L [268-700 mg/dL]) until 6 hours later when IV aspart insulin CRI began (20.1 mmol/L [363 mg/dL]; range, 9.4-26.1 mmol/L [169-470 mg/dL], P = 0.03). No adverse effects were observed in association with IV insulin aspart administration. Median cost of hospitalization was US$3,477 (range, US$1,483-10,469). Median total units per kilogram of administered IV insulin aspart was 2.97 U/kg (range, 2.04-10.52 U/kg). Intravenous CRI of insulin aspart is a safe and effective treatment for DKA in dogs. IV fluid resuscitation is recommended prior to insulin administration.

Segmentation of the thalamus based on BOLD frequencies affected in temporal lobe epilepsy.

Temporal lobe epilepsy is associated with functional changes throughout the brain, particularly including a putative seizure propagation network involving the hippocampus, insula, and thalamus. We identified a specified frequency range where functional connectivity in this network was related to duration of disease. Then, to identify specific thalamic nuclei involved in seizure propagation, we determined the subregions of the thalamus that have increased resting functional oscillations in this frequency range. Resting-state functional magnetic resonance imaging (fMRI) was acquired from 20 patients with unilateral temporal lobe epilepsy (TLE; 14 right and 6 left) and 20 healthy controls who were each age and gender matched to a specific patient. Wavelet-based fMRI connectivity mapping across the network was computed at each frequency to determine those frequencies where connectivity significantly decreases with duration of disease consistent with impairment due to repeated seizures. The voxel-wise power of the spontaneous blood oxygenation fluctuations of this frequency band was computed in the thalamus of each subject. Functional connectivity was impaired in the proposed seizure propagation network over a specific range (0.0067-0.013Hz and 0.024-0.032Hz) of blood oxygenation oscillations. Increased power in this frequency band (<0.032Hz) was detected bilaterally in the pulvinar and anterior nucleus of the thalamus of healthy controls, and was increased over the ipsilateral thalamus compared to the contralateral thalamus in TLE. This study identified frequencies of impaired connectivity in a TLE seizure propagation network and used them to localize the anterior nucleus and pulvinar of the thalamus as subregions most susceptible to TLE seizures. Further examinations of these frequencies in healthy and TLE subjects may provide unique information relating to the mechanism of seizure propagation and potential treatment using electrical stimulation.

Frequency-Specific Alterations of Local Synchronization in Idiopathic Generalized Epilepsy.

Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a "conscious perception network," which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands.

Local Activity and Causal Connectivity in Children with Benign Epilepsy with Centrotemporal Spikes

The aim of the current study was to localize the epileptic focus and characterize its causal relation with other brain regions, to understand the cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 37 children with BECTS and 25 children matched for age, sex and educational achievement. We identified the potential epileptogenic zone (EZ) by comparing the amplitude of low frequency fluctuation (ALFF) of spontaneous blood oxygenation level dependent fMRI signals between the groups. Granger causality analysis was applied to explore the causal effect between EZ and the whole brain. Compared with controls, children with BECTS had significantly increased ALFF in the right postcentral gyrus and bilateral calcarine, and decreased ALFF in the left anterior cingulate cortex, bilateral putaman/caudate, and left cerebellum. ALFF values in the putaman/caudate were positively correlated with verbal IQ scores in patients. The ALFF values in cerebellum and performance IQ scores were negatively correlated in patients. These results suggest that ALFF disturbances in the putaman/caudate and cerebellum play an important role in BECTS cognitive dysfunction. Compared with controls, the patients showed increased driving effect from the EZ to the right medial frontal cortex and posterior cingulate cortex and decreased causal effects from the EZ to left inferior frontal gyrus. The causal effect of the left inferior frontal gyrus negatively correlated with disease duration, which suggests a relation between the epileptiform activity and language impairment. All together, these findings provide additional insight into the neurophysiological mechanisms of epilepitogenisis and cognitive dysfunction associated with BECTS.

The spontaneous arterial blood pressure rise after aneurysmal subarachnoid hemorrhage – A biphasic phenomenon

ObjectivesA spontaneous blood pressure (BP) rise is frequently observed after aneurysmal subarachnoid hemorrhage (aSAH). The current study was designed to characterize the time course of this BP rise and its relation to clinical and radiological parameters. MethodsThe diastolic (DBP), mean (MAP), and systolic (SBP) BP values were determined in 61 aSAH patients from day 0 to 9. The patient's initial status was evaluated by the world federation of neurological surgeons scale and the Hijdra scale. The clinical outcome was quantified by the modified Rankin Scale, the Glasgow Outcome Scale Extended, and the National Institute of Health Stroke Scale. The degree of proximal and global vasospasm was calculated by comparison of the baseline angiography on day 0 and the control angiography on day 8. Furthermore, the influence of propofol and norepinephrine application was analyzed. ResultsDBP, MAP, and SBP demonstrated an early rise in all patients from day 2 till 5 (p<0.001) and remained hypertensive until day 9. No significant correlation could be detected between this early BP rise and most clinical and radiological variables. From day 8 onwards, a divergence of the SBP courses was detected between patients with severe vs. non-severe global vasospasm. There was a secondary, norepinephrine independent SBP rise in patients with severe global vasospasm that significantly correlated with the initial Hijdra-scale and an unfavorable clinical outcome. ConclusionsThe results demonstrate a biphasic BP course with a uniform early BP rise in all patients and an additional delayed SBP rise in patients with severe global vasospasm.

Contribution Of The Skeletal Muscle Pump To Blood Flow At The Onset Of Contractions

There is a substantial reserve for increased skeletal muscle blood flow in response to exercise; however, the interaction of neural regulation, vasoactive metabolites, and mechanical characteristics are incompletely understood. The potential contribution of skeletal muscle contraction, the muscle pump (MP), to exercise hyperemia remains in question. PURPOSE: To determine MP contribution to muscle blood flow during transitions from rest to various metabolic rates. METHODS: Canine gastrocnemius muscle (n=7) was isolated and stimulated to produce rhythmic isometric tetanic contractions. The total blood flow (Qwc) kinetics were fitted by a mono-exponential function (tau), and the blood flow response to contraction with the mechanical contribution of MP removed (Qnc) was calculated. The Qnc calculation estimated blood flow in each contraction cycle as a linear variation of blood flow from a point immediately prior to, until the end of each contraction. The following transitions were investigated with spontaneous blood flow response intact: rest to tetanic contractions of 1/3 s; rest to 2/3 s; rest to 1/1 s; and during the transition from 1/3 s to 2/3s. RESULTS: During 1/3 s stimulation, Qnc exceeded Qwc by the second contraction, indicating a negative contribution of MP to total flow from that point on. During 2/3 s stimulation, Qwc exceeded Qnc for at least six contractions but declined rapidly to a negative contribution beyond 20 s. During 1/1 s stimulation, MP contribution declined from onset but Qwc remained greater than Qnc throughout indicating a positive contribution to total flow. In all transitions tau was not different (p=ns) between Qwc and Qnc: 1/3 s stimulation rate, tau = 12.8 ± 5.5 s vs 11.8 ± 3.2 s, respectively; rest to 2/3 s, tau = 25.6 ± 12.0 s vs 22.1 ± 1.3 s; rest to 1/1 s, tau = 16.7 ± 3.0 s vs 22.1 ± 1.3 s; transition from 1/3 s to 2/3s, tau = 21.2 ± 3.4 s vs 21.7 ± 4.8 s. CONCLUSION: MP likely contributes to local perfusion at exercise onset with diminishing returns as rhythmic contractions continue. The benefit to total skeletal muscle blood flow contributed by MP is dependent on contraction frequency. Supported by BBSRC UK, BB/F019521/1.

Influence of Age on Blood Pressure Variability and Baroreceptor Sensitivity in Response to Acute Exercise

Aging and depressed spontaneous baroreceptor sensitivity (sBRS) and blood pressure variability (BPV) have been linked to negative cardiovascular outcomes. Understanding the interaction between agin...

Pioglitazone treatment enhances the sympathetic nervous system response to oral carbohydrate load in obese individuals with metabolic syndrome

ContextInsulin resistance is associated with blunted sympathetic nervous system (SNS) response to carbohydrate ingestion which may contribute to postprandial hypotension and impaired body weight homeostasis. ObjectiveThis study was conducted to examine the effects of pharmacological insulin sensitization on whole-body norepinephrine kinetics during a standard 75-g oral glucose tolerance test (OGTT) in obese, insulin resistant subjects with metabolic syndrome. MethodsUn-medicated individuals (n=42, mean age 56±0.8yrs, body mass index 34±0.6kg/m2) were randomised to 12-weeks pioglitazone (PIO, 15mg for 6weeks, then 30mg daily) or placebo using a double-blind, parallel group design. Whole-body norepinephrine kinetics (arterial norepinephrine concentration, calculated spillover and clearance rates), spontaneous cardiac baroreflex sensitivity, heart rate and blood pressure were measured at times 0, 30, 60, 90 and 120minutes during OGTT. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M) and Matsuda index. ResultsPIO increased clamp derived glucose utilisation by 35% (P<0.001) and there were concurrent reductions in inflammatory status and plasma triglycerides (P<0.05). Fasting norepinephrine kinetic parameters were unaltered. PIO treatment was associated with lower plasma insulin incursions, greater reduction in diastolic blood pressure and enhanced baroreflex sensitivity during OGTT (P all <0.05). The overall norepinephrine spillover response (AUC0–120) increased significantly in the PIO group (group × time interaction, P=0.04), with greatest increment at 30minutes post-glucose (101±38ng/min at baseline versus 241±48ng/min post treatment, P=0.04) and correlated with percent improvement in M. ConclusionsPIO enhances the early postprandial SNS response to carbohydrate ingestion.

Abstract W P2: Timeline of Blood Pressure Changes After Intra-arterial Therapy For Acute Ischemic Stroke Based on Recanalization Status

Introduction: Arterial recanalization with intravenous thrombolysis early for acute ischemic stroke (AIS) has been reported to be associated with spontaneous blood pressure (BP) reduction compared to those without recanalization. We investigated the course of BP after intra-arterial therapy (IAT) for AIS. Methods: Retrospective study from 1/08-12/12 of AIS patients who underwent IAT for ICA/M1 occlusions with TICI 0 flow was conducted. Cases under general anesthesia were excluded. BP recorded before, and at hourly intervals for 36 hours post procedure was collected. The average hourly BP, and the difference in hourly BP from pre-procedure baseline was calculated and compared by recanalization status. Successful recanalization was defined as TICI2b-3. Results: Sixty-two patients consisting of 37 (59.7%) with TICI2b-3 (Group R) and 25 with TICI 0-2a (Group NR) recanlization were included. Baseline characteristics were similar except for greater frequency of IV tPA administration in group R (51.3% vs. 20.8%, p 0.017). Average systolic BP (SBP) pre-procedure was similar in both both groups (R 158 vs NR 154 mm Hg, p 0.521). SBP decreased significantly at the end of procedure in both groups (Fig a,b), but without inter-group difference (Fig c). With time however, there was significantly lower average SBP, and greater SBP drop from baseline in the R group compared to NR group, but this persisted only till hour 12. (Fig 1c,d) Similar trend was observed with the mean arterial BP. Conclusions: BP after IAT differed significantly based on recanalization status and the difference was early. Endogenous drive to increase BP to maintain cerebral perfusion may account for the findings. This may have implications for BP management post IAT.

Frequency of spontaneous BOLD signal shifts during infancy and correlates with cognitive performance

Numerous studies have been conducted to delineate the early development of different functional networks, based on measuring the temporal synchronization of spontaneous blood oxygenation level-dependent (BOLD) signals acquired using resting state functional MRI (rsfMRI). However, little attention has been paid to the change of the frequency properties of these signals during early brain development. Such frequency properties may reflect important physiological changes and potentially have significant cognitive consequences. In this study, leveraging a large (N=86 subjects), longitudinal sample of human infants scanned during the first two years of life, we aimed to specifically delineate the developmental changes of the frequency characteristics of spontaneous BOLD signals. Both whole-brain and network-level examinations were carried out and the frequency-behavior relationship was explored. Our results revealed a clear right-ward shift of BOLD signal frequency during the first year of life. Moreover, the power at the peak-frequency for sensorimotor and lateral visual networks correlates with domain-specific Mullen Scales in 1-year-olds, suggesting the behavioral significance of the BOLD signal frequency during infancy. Findings from this study shed light into early functional brain development and provide a new perspective for future searches for functional developmental abnormalities.