Increase In Cerebral Blood Flow Research Articles

Spatiotemporal cerebral blood flow dynamics underlies emergence of the limbic-sensorimotor-association cortical gradient in human infancy

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across the lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we find the emergence of the cortical hierarchy revealed by the highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increases in a biphasic pattern featured by initial rapid and subsequently slower rate, and break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices are associated with enhanced language and motor skills, and frontoparietal association cortices with cognitive skills. The study discovers emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.

A timeline study on vascular co-morbidity induced cerebral endothelial dysfunction assessed by perfusion MRI

Endothelial dysfunction is considered a key element in the early pathogenesis of neurodegenerative disorders. Dysfunction of the cerebral endothelial cells can result in dysregulation of cerebral perfusion and disruption of the Blood Brain Barrier (BBB), leading to brain damage, neurodegeneration and cognitive decline. It has been shown that the presence of modifiable risk factors exacerbates endothelial dysfunction. This study primarily aimed to identify which among various perfusion MRI methodologies could be effectively utilized to non-invasively identify early pathological alterations as a result of endothelial dysfunction. We compared these perfusion MRI measurements to invasive immunohistochemistry to detect early pathological alterations in the cerebral vasculature of a rat model of multiple cardiovascular co-morbidities (the ZSF1 Obese rat) at several stages of the cerebrovascular pathology. We observed cerebral hyperperfusion, expressed by increased Cerebral Blood Flow (CBF) and increased BBB permeability in the ZSF1 Obese rats, at an early stage of disease development. The increase in CBF observed with Arterial Spin Labeling (ASL) was lost during later stages of disease progression. These findings are in line with recent clinical findings in early stages of Alzheimer's disease (AD), that also show early increases in CBF.

All-optics technique for monitoring absolute cerebral blood flow: validation against magnetic resonance imaging perfusion.

The ability to monitor cerebral blood flow (CBF) at the bedside is essential to managing critical-care patients with neurological emergencies. Diffuse correlation spectroscopy (DCS) is ideal because it is non-invasive, portable, and inexpensive. We investigated a near-infrared spectroscopy (NIRS) approach for converting DCS measurements into physiological units of blood flow. Using magnetic resonance imaging perfusion as a reference, we investigated the accuracy of absolute CBF measurements from a bolus-tracking NIRS method that used transient hypoxia as a flow tracer and hypercapnia-induced increases in CBF measured by DCS. Twelve participants (7 female, years) completed a hypercapnia protocol with simultaneous CBF recordings from DCS and arterial spin labeling (ASL). Nine participants completed the transient hypoxia protocol while instrumented with time-resolved NIRS. The estimate of baseline CBF was subsequently used to calibrate hypercapnic DCS data. Moderately strong correlations at baseline ( and ) and during hypercapnia ( and ) were found between CBF values from calibrated DCS and ASL (range 34 to ). Results demonstrated the feasibility of an all-optics approach that can both quantify CBF and perform continuous perfusion monitoring.

Regulation of Cerebral Blood Flow Velocity by Transcutaneous Electrical Nerve Stimulation: A Preliminary Study

Objectives: An excessive and abrupt increase in cerebral blood flow may cause blood vessel damage, leading to stroke. Therefore, appropriate methods to immediately regulate blood flow velocity are important. Through an analysis of 31 healthy adults, we therefore investigated whether stimulating the common carotid artery (CCA) using transcutaneous electrical nerve stimulation (TENS) could modulate blood flow velocity in the CCA. Methods: Three stimulation intensities (below-threshold, threshold, and above-threshold) were applied in a random order. Blood velocity changes were examined by the measurement of peak systolic velocity (PSV) with Doppler ultrasound before, during, and after TENS stimulation. To evaluate arterial stiffness, pulse wave velocity (PWV) was calculated using CCA diameter, and blood pressure was measured before and after stimulation. Results: PSV changes in the below-threshold level were significant (p = 0.028). The PSV after below-threshold stimulation was significantly decreased by 2.23% compared to that before stimulation (p = 0.031). PWV showed no significant differences; however, a nonsignificant increase was observed immediately after stimulation only in the above-threshold condition. Above-threshold stimulation can increase vascular tone by activating the sympathetic nerve, possibly triggering vasoconstriction. Conclusions: A decrease in blood flow velocity may not be expected upon the above-threshold stimulation. In contrast, the below-threshold stimulation immediately reduces blood flow velocity, without significantly affecting hemodynamic function, such as arterial flexibility. Therefore, this short-term and low electrical stimulation technique can help to lower vascular resistance and prevent vascular damage from rapid blood flow velocity.

Breath-hold calibrated fMRI mapping of absolute cerebral metabolic rate of oxygen metabolism (CMRO2): An assessment of the accuracy and repeatability in a healthy adult population

Abstract We previously introduced a calibrated fMRI framework that utilises respiratory modulation with only a single gas (CO2) to map the grey matter (GM) cerebral metabolic rate of oxygen consumption (CMRO2). The method decouples and estimates the cerebral blood volume (CBV) and the oxygen extraction fraction (OEF) from a single measure of the maximum BOLD modulation. The method links the two parameters of interest with a model of oxygen diffusion from capillaries to mitochondria which incorporates the cerebral blood flow (CBF). Here, we apply this framework to gas-free breath-hold calibrated fMRI (bhc-fMRI), where simultaneous BOLD and ASL acquisitions are combined with modulation of arterial CO2 through repeated breath-holding. The accuracy and repeatability of the method is assessed in 33 healthy volunteers at rest and during continuous visual stimulation. Average GM OEF estimated from bhc-fMRI was 0.37 ± 0.04, indicating a small bias of 0.04 (with limits of agreement from -0.11 to 0.12) compared to the whole brain OEF of 0.32 ± 0.07 estimated from sagittal sinus using T2 Relaxation Under Spin Tagging (TRUST). The within-session repeatability of GM estimates were moderate to good for OEF, with ICC = 0.75 (0.56–0.87) and good to excellent for CMRO2, with ICC = 0.88 (0.74–0.94). An ROI analysis in the visual cortex found an average CBF increase of 16%, a CMRO2 increase of 12%, and an OEF decrease of 3% during the visual stimulation. The bhc-fMRI measurement of CMRO2 is simple to implement, has comparable accuracy and repeatability to existing gas-based methods, and is sensitive to modulations in metabolism during functional hyperaemia.

Neurovascular coupling and CO2 interrogate distinct vascular regulations

Neurovascular coupling (NVC), which mediates rapid increases in cerebral blood flow in response to neuronal activation, is commonly used to map brain activation or dysfunction. Here we tested the reemerging hypothesis that CO2 generated by neuronal metabolism contributes to NVC. We combined functional ultrasound and two-photon imaging in the mouse barrel cortex to specifically examine the onsets of local changes in vessel diameter, blood flow dynamics, vascular/perivascular/intracellular pH, and intracellular calcium signals along the vascular arbor in response to a short and strong CO2 challenge (10 s, 20%) and whisker stimulation. We report that the brief hypercapnia reversibly acidifies all cells of the arteriole wall and the periarteriolar space 3–4 s prior to the arteriole dilation. During this prolonged lag period, NVC triggered by whisker stimulation is not affected by the acidification of the entire neurovascular unit. As it also persists under condition of continuous inflow of CO2, we conclude that CO2 is not involved in NVC.

Changes in indicators of cerebral metabolic stress following treatment with voxelotor in children and adolescents with sickle cell anemia

AbstractVoxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin‐oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction. We followed four patients for 2–5 months during and/or after voxelotor therapy. This study showed no observable increase in cerebral blood flow or oxygen extraction fraction during treatment.

Spatiotemporal cerebral blood flow dynamics underlies emergence of the limbic-sensorimotor-association cortical gradient in human infancy.

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across the lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we found the emergence of the cortical hierarchy revealed by the highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increased in a biphasic pattern with initial rapid and sequentially slower rate, with break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices were associated with enhanced language and motor skills, and frontoparietal association cortices for cognitive skills. The study discovered emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy, and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.

Left hemiparesis due to space-occupying lesion in pregnancy

HIGHLIGHTS 1. Present a case report detailing the diagnosis and management of a space-occupying lesion identified late in pregnancy.2. Current studies consistently indicate that the optimal period for tumor removal during pregnancy is the second trimester, balancing maternal and fetal outcomes. This case report contributes to the existing literature by providing a practical reference for managing space-occupying lesions in accordance with the latest evidence. ABSTRACT Objectives: The objective of this study was to present the findings from cases of space-occupying lesions (SOL) that were diagnosed late in pregnancy. This case report aimed to highlight the importance of considering space-occupying lesions as a differential diagnosis in instances of hemiparesis during pregnancy, thereby raising clinical awareness and improving diagnostic accuracy. Case Report: A female patient aged 30 years 34 weeks pregnant came with complaints of slurred speech since 3 months before entering the hospital accompanied by weakness in the left limbs since 3 months before admission. The patient felt weak and fell in the bathroom 2 times, at the office and at home. The patient had a history of taking aspilet for 1.5 months due to a misdiagnosis as a stroke in a Type B hospital and stopped when she came to the obstetric emergency room at a Type A Hospital for the first time. Cardiothoracograph examination shows a picture of a silent baby. Computed Tomography (CT) Scan examination showed a picture of hydrocephalus. Conclusion: To date, it has not been proven that pregnancy triggers brain tumors. However, increased blood supply to the brain during pregnancy may lead to tumor growth. This is also evident in this case where there is an increase in maternal blood volume and subsequent cerebral blood flow, causing an increase in the size of the SOL. On the other hand, there is no evident that brain tumors directly harm the fetus, though fetal hypoxia may occur indirectly due to maternal respiratory failure.

Perioperative Craniotomy Excision of Dextra Subtemporal Tumor with Thiopental, Sufentanyl and Invasive Monitor

Intracranial masses can arise from a variety of aetiologies, including congenital, neoplastic, infectious, or vascular processes, each requiring distinct diagnostic and management considerations. Establishing the presence or absence of intracranial hypertension is a critical component of the preoperative evaluation for patients undergoing craniotomy for mass lesions. Hemodynamic is an examination of the physical aspects of blood circulation, cardiac function and physiological characteristics of peripheral vasculature. A 74 year old man was admitted to the hospital because of cephalgia, and left limb weakness. Previously, the patient often felt headaches that came and went since six months ago. Three days before being admitted, the patient felt weak in his left limb and experienced decreasing in consciousness. The patient was given thiopental because the onset of action of thiopental was very short. Administration of intravenous doses of thiopental can cause cerebral vasoconstriction. Sufentanil was administered as an analgesic, because sufentanil is an opioid that has a rapid onset and analgesic potential, compared to fentanyl, intravenous and sufentanil is 5–10 times stronger. This efficacy to maintain adequate cerebral perfusion pressure (CPP), reduce cerebral blood flow (CBF), maintain normal autoregulation, reduce cerebral metabolic rate for oxygen (CMRO2). Arterial cannulation with continuous transduction is considered the gold standard for blood pressure monitoring during anaesthetic procedures. Rapid fluctuations in blood pressure can occur due to patient positioning, surgical manipulation, and the effects of anaesthetics drugs, and close monitoring of these changes is crucial for maintaining hemodynamic stability. The impact of anaesthetic management on CBF is also an integral component of neuroanesthesia, as increases in CBF are associated with increases in cerebral blood volume (CBV). An effective neuro-anesthesia management program that incorporates both invasive blood pressure monitoring and optimization of cerebral perfusion that can help preserving hemodynamic stability and improving outcomes for patients undergoing craniotomy surgery

The role of citicoline in the correction of cerebral blood flow disorders in patients with coronary artery disease in combination with COVID-19

OBJECTIVE. To evaluate the effect of citicoline on cerebral blood flow and microembolic signals (MES) after 6 months of treatment in patients with coronary artery disease combined with coronavirus disease (COVID-19). MATERIALS AND METHODS. A prospective study of 68 patients with coronary artery disease with confirmed COVID-19 by PCR was conducted. Group I (n=35) included patients with coronary artery disease in combination with COVID-19, who, in addition to standard therapy of cerebrovascular disease, received citicoline (500 mg twice daily) for 6 months after discharge from the hospital. The comparison group (group II; n=33) consisted of patients who did not receive citicoline. Cerebral blood flow, peak systolic velocity in extracranial and intracranial vessels were determined, and 1-hour transcranial monitoring to detect MES were performed. Patients were re-examined in 6 months. RESULTS. At the initial examination of patients, cerebral blood flow and the number of MES did not differ significantly. After 6 months, there was an increase in cerebral blood flow in the cerebral arteries, as well as a decrease in MES in patients taking citicoline, whereas in group II there was no positive dynamics of this ratio. A direct correlation between plasma C-reactive protein, D-dimer and MES was found in patients of both groups. After 6 months of treatment, C-reactive protein and D-dimer decreased in both groups equally. CONCLUSIONS. The obtained results of improvement of cerebral perfusion, blood rheology, due to the anti-inflammatory effect, stabilising function of citicoline on phospholipid membranes of cerebral vascular endothelium, neurons and glial elements allow the use of citicoline in patients with coronary artery disease in combination with COVID-19 to reduce the negative impact of COVID-19 on the central nervous system.

Differentiation Between High-Grade Glioma and Brain Metastasis Using Cerebral Perfusion-Related Parameters (Cerebral Blood Volume and Cerebral Blood Flow): A Systematic Review and Meta-Analysis of Perfusion-weighted MRI Techniques.

Distinguishing high-grade gliomas (HGGs) from brain metastases (BMs) using perfusion-weighted imaging (PWI) remains challenging. PWI offers quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), but optimal PWI parameters for differentiation are unclear. To compare CBF and CBV derived from PWIs in HGGs and BMs, and to identify the most effective PWI parameters and techniques for differentiation. Systematic review and meta-analysis. Twenty-four studies compared CBF and CBV between HGGs (n = 704) and BMs (n = 488). Arterial spin labeling (ASL), dynamic susceptibility contrast (DSC), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast-enhanced (DSCE) sequences at 1.5 T and 3.0 T. Following the PRISMA guidelines, four major databases were searched from 2000 to 2024 for studies evaluating CBF or CBV using PWI in HGGs and BMs. Standardized mean difference (SMD) with 95% CIs was used. Risk of bias (ROB) and publication bias were assessed, and I2 statistic was used to assess statistical heterogeneity. A P-value<0.05 was considered significant. HGGs showed a significant modest increase in CBF (SMD = 0.37, 95% CI: 0.05-0.69) and CBV (SMD = 0.26, 95% CI: 0.01-0.51) compared with BMs. Subgroup analysis based on region, sequence, ROB, and field strength for CBF (HGGs: 375 and BMs: 222) and CBV (HGGs: 493 and BMs: 378) values were conducted. ASL showed a considerable moderate increase (50% overlapping CI) in CBF for HGGs compared with BMs. However, no significant difference was found between ASL and DSC (P = 0.08). ASL-derived CBF may be more useful than DSC-derived CBF in differentiating HGGs from BMs. This suggests that ASL may be used as an alternative to DSC when contrast medium is contraindicated or when intravenous injection is not feasible. Stage 2.

TPA supplementation preserves neurovascular and cognitive function in Tg2576 mice.

Amyloid beta (Aβ) impairs the cerebral blood flow (CBF) increase induced by neural activity (functional hyperemia). Tissue plasminogen activator (tPA) is required for functional hyperemia, and in mouse models of Aβ accumulation tPA deficiency contributes to neurovascular and cognitive impairment. However, it remains unknown if tPA supplementation can rescue Aβ-induced neurovascular and cognitive dysfunction. Tg2576 mice and wild-type littermates received intranasal tPA (0.8mg/kg/day) or vehicle 5 days a week starting at 11 to 12 months of age and were assessed 3 months later. Treatment of Tg2576 mice with tPA restored resting CBF, prevented the attenuation in functional hyperemia, and improved nesting behavior. These effects were associated with reduced cerebral atrophy and cerebral amyloid angiopathy, but not parenchymal amyloid. These findings highlight the key role of tPA deficiency in the neurovascular and cognitive dysfunction associated with amyloid pathology, and suggest potential therapeutic strategies involving tPA reconstitution. Amyloid beta (Aβ) induces neurovascular dysfunction and impairs the increase of cerebral blood flow induced by neural activity (functional hyperemia). Tissue plasminogen activator (tPA) deficiency contributes to the neurovascular and cognitive dysfunction caused by Aβ. In mice with florid amyloid pathology intranasal administration of tPA rescues the neurovascular and cognitive dysfunction and reduces brain atrophy and cerebral amyloid angiopathy. tPA deficiency plays a crucial role in neurovascular and cognitive dysfunction induced by Aβ and tPA reconstitution may be of therapeutic value.

Menstrual cycle status does not impact exercise-based changes in cerebral blood flow or executive function benefits

ABSTRACT A single bout of exercise enhances executive function (EF) and may relate to an increase in cerebral blood flow (CBF). A limitation in the current literature is that biologically female participants are underrepresented given some evidence that changes in hormone levels across the menstrual cycle impact physiological and psychological variables. Here, biologically female participants completed separate single bouts of moderate intensity exercise (80% of estimated lactate threshold) during the follicular (FOL) and luteal (LUT) phases of their menstrual cycle. In addition, biologically male participants completed a same duration/intensity exercise session. Middle cerebral artery velocity (MCAv) was used to estimate CBF and pre- and postexercise EF was assessed via the antisaccade task. Results showed that resting MCAv was larger in the LUT than FOL phase; however, the exercise-mediated increase in MCAv was equivalent between menstrual cycle phases, and between female and male participants. Antisaccade reaction times reliably decreased from pre- to postexercise and frequentist and non-frequentist statistics demonstrated that the magnitude of the decrease was equivalent across FOL and LUT phases, and between female and male participants. Thus, results evince that menstrual cycle status should not serve as a basis limiting biologically female participants’ inclusion in research examining exercise and EF.

Parvalbumin interneuron activity induces slow cerebrovascular fluctuations in awake mice.

Neuronal regulation of cerebrovasculature underlies brain imaging techniques reliant on cerebral blood flow (CBF) changes. However, interpreting these signals requires understanding their neural correlates. Parvalbumin (PV) interneurons are crucial in network activity, but their impact on CBF is not fully understood. Optogenetic studies show that stimulating cortical PV interneurons induces diverse CBF responses, including rapid increases, decreases, and slower delayed increases. To clarify this relationship, we measured hemodynamic and neural responses to optogenetic stimulation of PV interneurons expressing Channelrhodopsin-2 during evoked and ongoing resting-state activity in the somatosensory cortex of awake mice. Two-photon microscopy (2P) Ca2+ imaging showed robust activation of PV-positive (PV+) cells and inhibition of PV-negative (PV-) cells. Prolonged PV+ cell stimulation led to a delayed, slow CBF increase, resembling a secondary peak in the CBF response to whisker stimulation. 2P vessel diameter measurements revealed that PV+ cell stimulation induced rapid arterial vasodilation in superficial layers and delayed vasodilation in deeper layers. Ongoing activity recordings indicated that both PV+ and PV- cell populations modulate arterial fluctuations at rest, with PV+ cells having a greater impact. These findings show that PV interneurons generate a complex depth-dependent vascular response, dominated by slow vascular changes in deeper layers.

Hot head-out water immersion increases internal carotid artery shear rate but does not alter intracranial vascular reactivity to carbon dioxide

Acute head-out water immersion (HOWI) in hot water increases cerebral blood flow (CBF) until core temperature rises by ~1.0°C. The increase in CBF may promote increases in arterial shear rate that could enhance cerebrovascular reactivity to CO2 (CVRCO2) as a result of elevated nitric oxide (NO) bioavailability. An increase in NO bioavailability improves peripheral vasodilator function, and therefore, a similar response may occur in the cerebral vasculature. This likely only aids in cerebral vasodilation during hypercapnia, and not cerebral vasoconstriction during hypocapnia. However, it is unclear if a single session of hot HOWI alters cerebral artery shear rate and CVRCO2 to hyper- and hypocapnia. Purpose: We tested the hypotheses that during a single session of hot HOWI (39°C), cerebral artery shear rate and hypercapnic CVRCO2 would be greater and hypocapnic CVRCO2 would be lower compared to temperate HOWI (35°C). Methods: Eighteen healthy participants (age: 25±5 y, 6 women) completed two experimental visits. Middle and posterior cerebral artery blood velocities (transcranial Doppler; MCAv and PCAv) were continuously recorded. Blood velocities and diameters of the right internal carotid artery (ICA) and vertebral artery (VA) were obtained via dual-mode Doppler ultrasound to calculate shear rate. Hypocapnic and hypercapnic CVRCO2 were assessed in the MCA and PCA during self-paced hyperventilation (until PETCO2 decreased by 10 mmHg from baseline) and during 30 s of 7% CO2 inhalation, respectively. Measures were completed before immersion (PRE) and after a +1.0°C increase in core temperature during hot HOWI and time-matched during temperate HOWI. Data are reported as mean ± SD. Results: There were no differences between conditions at PRE. MCAv (55±9 vs. 64±12 cm/s; P=0.01) and PCAv (29±5 vs. 39±7 cm/s; p&lt;0.01) were lower in hot vs. temperate HOWI at +1.0°C. ICA shear rate was greater in hot vs. temperate HOWI at +1.0°C (247±51 vs. 180±43 s−1; p&lt;0.01) but VA shear rate did not differ between conditions (P=0.78). There were no differences between conditions for hypercapnic CVRCO2 (MCA: P =0.48, PCA: P=0.43) or hypocapnic CVRCO2 (MCA: P=0.18). A condition effect was observed for PCA hypocapnic CVRCO2 (p&lt;0.01), but multiple comparisons did not reveal where differences occurred (all P≥0.10). Conclusion: Hot head out water immersion elicits similar changes in hemodynamics and CVRCO2 in intracranial arteries (i.e., MCA and PCA) as temperate head out water immersion. Hot head out water immersion produces a greater shear rate in the ICA compared to temperate water, which may be beneficial for cerebrovascular health if done recurrently. This study was partially supported by the Mark Diamond Research Fund at the University at Buffalo and the Offce of Naval Research Director of Research Early Career Grant (N00014-17-1-2878). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Treatment of Hypotension with Phenylephrine Increases Cerebral Microvascular Perfusion in a Rat Model of Acute Hemodilution

Intraoperative blood loss is associated with reduced mean arterial blood pressure (MAP), which may endanger vital organ perfusion, including the brain. Phenylephrine (PE), an α1-receptor agonist, is clinically utilized to treat intraoperative hypotension through vasoconstriction of resistance arterioles. Clinical studies suggest that raising MAP with PE may decrease perfusion to vital organs such as the brain. Experimental studies suggest that lower α-receptor density in the cerebral resistance arteries may lead to preserved brain perfusion after PE administration. We hypothesize that treatment of hypotension with PE will result in preserved brain perfusion due to different microvascular blood flow and tissue oxygen tension (pO2) responses in the brain and skeletal muscle in an experimental rat model. With Animal Care and Use Committee approval in accordance with ARRIVE-2 guidelines, spontaneously breathing anesthetized rats (1.5% isoflurane) underwent hemodilution by exchanging 40-50% estimated blood volume 1:1 with saline over 10 minutes to achieve a 10-20 mmHg drop in MAP. MAP (tail artery) was measured continuously. Hypotension was treated with PE (10-20 μg/kg/min iv) to increase MAP to a target above baseline MAP. Shed blood was re-infused after stopping the PE infusion. Microvascular blood flow (Oxyflo; Oxford Optronix, Oxford, UK, n=7) or microvascular pO2 (OxyLED, Oxyphor G4, Oxygen Enterprises Ltd., Philadelphia, PA, n=6) were measured continuously in the cerebral cortex (burr hole) and biceps femoris muscle simultaneously in each rat. Results were analyzed via one or two-way ANOVA, with significance achieved at p&lt;0.05. Baseline and post-hemodilution MAP values were comparable in both groups. PE infusion increased MAP to a mean level near 100 mmHg in both groups (p&lt;0.05). Microvascular blood flow and tissue pO2 were greater in the brain as compared to the muscle at all time points (p&lt;0.01 for both). PE infusion resulted in an increase in cerebral microvascular blood flow from baseline (1465±689 vs. 687±453 blood perfusion units (BPU); p&lt;0.001) that was sustained after discontinuing PE and during blood reinfusion. No changes in muscle microvascular flow were observed after PE infusion (294±129 vs. 168±113 BPU). A sustained increase in cerebral microvascular pO2 was measured following PE infusion (50.2±8.6 vs. 40.6±4.6 mmHg; p=0.02), whereas muscle tissue pO2 did not change (22.2±5.6 vs. 25.0±2.5 mmHg). A differential blood flow and microvascular pO2 response was observed following PE infusion in brain and skeletal muscle. Both cerebral microvascular blood flow and tissue pO2 demonstrated sustained increases after PE infusion. By contrast, no changes were observed in muscle microvascular blood flow and pO2. These results suggest that treatment of hypotension with PE administration preferentially increased cerebral vs. muscle perfusion in an experimental model of acute blood loss and fluid resuscitation. Canadian Anesthesiologists’ Society and University of Toronto Merit Award Support. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Global hyperperfusion after successful endovascular thrombectomy is linked to worse outcome in acute ischemic stroke

Patients with stroke may develop hyperperfusion after a successful endovascular thrombectomy (EVT). However, the relationship between post-EVT hyperperfusion and clinical outcomes remains unclear and requires further clarification. We reviewed consecutive patients with anterior circulation occlusion who were successfully recanalized with EVT. Based on post-EVT arterial spin-labeling images, hyperperfusion was categorized as follows: global hyperperfusion (GHP), increased cerebral blood flow (CBF) in ≥ 50% of the culprit vessel territory; focal hyperperfusion (FHP), increased CBF in < 50% of the culprit vessel territory; no hyperperfusion (NHP), no discernible CBF increase. Factors associated with hyperperfusion were assessed, and clinical outcomes were compared among patients under different hyperperfusion categories. Among 131 patients, 25 and 40 patients developed GHP and FHP, respectively. Compared to other groups, the GHP group had worse National Institutes of Health Stroke Scale score (GHP vs. NHP/FHP, 18.1 ± 7.4 vs. 12.3 ± 6.0; p < 0.001), a larger post-EVT infarct volume (98.9 [42.3–132.7] vs. 13.5 [5.0–34.1] mL; p < 0.001), and a worse 90-day outcome (modified Rankin Scale, 3 [1–4] vs. 2 [0–3]; p = 0.030). GHP was independently associated with infarct volume (B = 0.532, standard error = 0.163, p = 0.001), and infarct volume was a major mediator of the association of GHP with unfavorable outcomes (total effect: β = 0.176, p = 0.034; direct effect: β = 0.045, p = 0.64; indirect effect: β = 0.132, p = 0.017). Patients presenting with post-EVT GHP had poorer neurological prognosis, which is likely mediated by a large infarct volume.

Elevated plasma aldosterone impairs functional hyperemia and cognitive function

Aldosterone, a steroid hormone, plays an important role in blood pressure homeostasis and the maintenance of plasma electrolyte levels by activating the mineralocorticoid receptor (MR) in renal distal tubule and collecting duct epithelial cells. Recent studies revealed that MRs are also expressed in other tissues, including cardiac myocytes, vascular smooth muscle cells, and vascular endothelial cells (EC), and that elevated plasma aldosterone, termed hyperaldosteronemia (HA), has deleterious effects on the cardiovascular system. HA is present in 10-30% of hypertensive patients and unrecognized and asymptomatic HA is estimated to occur in &gt; 10% of individuals with normal blood pressure. Despite the high prevalence of HA, little is known about its impact on cerebral blood flow (CBF) regulation and brain health. This study focused on the physiological processes that support the on-demand delivery of blood to regions of heightened neuronal activity (functional hyperemia). Specifically, we examined the impact of HA on the recently discovered novel mechanism, termed capillary-to-arteriole signaling, through which capillaries and their strong inward rectifier K+ (Kir 2.1) channels play a significant role in functional hyperemia. Importantly, early deficits in functional hyperemia are a hallmark of small vessel diseases of the brain, which are significant contributors to cognitive impairment and dementia. Employing HA model mice, we examined the impact of HA on functional hyperemia, capillary-to-arteriole signaling, Kir2.1 channel activity in freshly isolated capillary ECs (cECs), and cognitive function. Functional hyperemia, measured as whisker stimulation-induced CBF increases using laser Doppler flowmetry, was impaired in HA animals compared to vehicle-treated animals. Retrograde capillary-to-arteriole signaling, evaluated as upstream arteriolar dilation in response to capillary stimulation with 10 mM K+ in Capillary-Parenchymal Arteriole (CaPA), preparations was significantly attenuated in HA mice. Furthermore, cEC Kir2.1 channel currents, recorded using the conventional whole-cell configuration of the patch-clamp technique, were significantly smaller in HA mice compared to vehicle-treated mice. Further, HA model animals obtained lower scores in the Novel Object Recognition test, indicating that cognitive function in the form of memory retention may be impacted by elevated plasma aldosterone. These data suggest that HA impairs functional hyperemia and cognitive function, and that HA may be a novel risk factor for vascular cognitive impairment. This work was supported by The National Institute of Health (P20-GM-135007 to MK and R01-HL-142888 to GCW). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cerebral blood flow regulation in hypobaric hypoxia: role of haemoconcentration.

During acute hypoxic exposure, cerebral blood flow (CBF) increases to compensate for the reduced arterial oxygen content (CaO2). Nevertheless, as exposure extends, both CaO2 and CBF progressively normalize. Haemoconcentration is the primary mechanism underlying the CaO2 restoration and may therefore explain, at least in part, the CBF normalization. Accordingly, we tested the hypothesis that reversing the haemoconcentration associated with extended hypoxic exposure returns CBF towards the values observed in acute hypoxia. Twenty-three healthy lowlanders (12 females) completed two identical 4-day sojourns in a hypobaric chamber, one in normoxia (NX) and one in hypobaric hypoxia (HH, 3500m). CBF was measured by ultrasound after 1, 6, 12, 48 and 96h and compared between sojourns to assess the time course of changes in CBF. In addition, CBF was measured at the end of the HH sojourn after hypervolaemic haemodilution. Compared with NX, CBF was increased in HH after 1h (P=0.001) but similar at all later time points (all P>0.199). Haemoglobin concentration was higher in HH than NX from 12h to 96h (all P<0.001). While haemodilution reduced haemoglobin concentration from 14.8 ± 1.0 to 13.9 ± 1.2g·dl-1 (P<0.001), it did not increase CBF (974 ± 282 to 872 ± 200ml·min-1; P=0.135). We thus conclude that, at least at this moderate altitude, haemoconcentration is not the primary mechanism underlying CBF normalization with acclimatization. These data ostensibly reflect the fact that CBF regulation at high altitude is a complex process that integrates physiological variables beyond CaO2. KEY POINTS: Acute hypoxia causes an increase in cerebral blood flow (CBF). However, as exposure extends, CBF progressively normalizes. We investigated whether hypoxia-induced haemoconcentration contributes to the normalization of CBF during extended hypoxia. Following 4 days of hypobaric hypoxic exposure (corresponding to 3500m altitude), we measured CBF before and after abolishing hypoxia-induced haemoconcentration by hypervolaemic haemodilution. Contrary to our hypothesis, the haemodilution did not increase CBF in hypoxia. Our findings do not support haemoconcentration as a stimulus for the CBF normalization during extended hypoxia.