Vein Cannulation Research Articles

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. Aim: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. Main methods: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. Key findings: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. Significance: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

Internal thoracic vein cannulation for venous port insertion

Internal thoracic vein cannulation for venous port insertion

Comparison of the scan-as-you-go technique with the short-axis out-of-plane technique on the incidence of posterior venous wall puncture in ultrasound-guided internal jugular vein cannulation - A randomised controlled trial.

Comparison of the scan-as-you-go technique with the short-axis out-of-plane technique on the incidence of posterior venous wall puncture in ultrasound-guided internal jugular vein cannulation - A randomised controlled trial.

Sildenafil improves hemodynamic changes caused by acute pulmonary embolism by inhibiting Rho kinase activity.

This study examined the effects of sildenafil on acute pulmonary embolism (APE) using a rat model. Sprague-Dawley rats were randomly divided into the sham, pulmonary thromboembolism (PTE), and sildenafil groups. The sham and PTE groups received normal saline once daily via gavage for 14 consecutive days, whereas the sildenafil group received sildenafil (0.5 mg/kg/day) once daily via gavage for 14 consecutive days. Autologous emboli were prepared from blood samples collected from the left femoral artery of rats in each group on day 13, and autologous emboli were injected into the jugular vein cannula of rats in the PTE and sildenafil groups on day 14. Sham-treated rats received the same volume of saline. Right systolic ventricular pressure (RVSP) and mean pulmonary arterial pressure (MPAP) were used to assess pulmonary embolism, and western blotting and enzyme-linked immunosorbent assay were used to detect relevant markers. The Rho kinase signaling pathway was significantly activated in rats with APE, and sildenafil significantly inhibited this activation. Sildenafil protected against APE through inhibiting Rho kinase activity, thereby reducing pulmonary vasoconstriction and decreasing elevated pulmonary arterial pressure. These findings might provide new ideas for the clinical treatment of acute pulmonary thromboembolism.

Subclavian Vein Cannulation via Supraclavicular or Infraclavicular Route Which is Better? A Prospective Randomized Controlled Trial.

The subclavian vein is frequently cannulated using ultrasound. There are two techniques of subclavian vein catheterization (SVC): Supraclavicular (SC) and infraclavicular (IC). Though the IC route is often preferred, the SC approach offers several distinct advantages. This study was planned to compare the technique of SVC using SC and IC approaches in terms of catheterization technique and complications in elective surgeries in adults. Sixty American Society of Anesthesiologists (ASA) 1, 2, or 3 adult patients posted for elective surgeries under general anesthesia were recruited. Patients were divided into SC or IC groups randomly. Right-sided subclavian vein was cannulated in both the groups (n = 30). Visualization time, Likert scale, subclavian vein diameter, skin-to-subclavian vein depth, number of attempts, puncture time, ease of guidewire insertion, catheter insertion time, and total procedural time were observed. A comparison of complications for each approach was noted. Total procedural time, time to visualization of the subclavian vein, and puncture time was lower for group SC and higher for group IC. Catheter insertion time was higher with the IC approach than with the SC approach. Better ultrasound view scores were seen in group SC than in group IC. The first attempt success rate was higher in group SC than in group IC. Comparatively, lower complications both during and after the procedure were noted in the SC approach than the IC approach. Ultrasonography (USG) guidance guided SC approach to access the subclavian vein is quicker, relatively secure, and a better technique than the IC approach. Additionally, the SC approach is associated with comparatively fewer immediate and delayed complications. Jaiswal P, Saini S, Chhabra PH. Subclavian Vein Cannulation via Supraclavicular or Infraclavicular Route Which is Better? A Prospective Randomized Controlled Trial. Indian J Crit Care Med 2024;28(4):375-380.

Complications of femoral access for hemodialysis: A surgical perspective

Background: Vascular access, especially arteriovenous fistula (AVF), is critical for patients requiring haemodialysis. Due to delayed diagnosis, late referral, poverty and limited availability of competent access surgeons, many patients commence haemodialysis without an AVF, hence the frequent use of venous catheters. Objectives: To assess the pattern of complications associated with repeated femoral punctures for haemodialysis. Materials and Methods: This is a multicentre prospective study conducted at the Cardiovascular units of the University of Port Harcourt Teaching Hospital, Port Harcourt and Federal Medical Centre, Umuahia between January 2017 and December 2022. 66 patients were recruited for the study. Data obtained were patients’ demography, complications of femoral access, surgical approach and outcome. Results: 15 patients presented with severe lower limb pains and inability to walk, 10 with fibrosis/ hardening of the skin of both groins, 8 with skin infection at the repeated puncture sites, 12 had Pseudoaneurysm of the superficial femoral artery (SFA), 6 had iatrogenic femoro-femoral Arteriovenous Fistula (AVF) of the SFA and superficial femoral vein (SFV), 5 had groin abscess. All the patients had internal jugular venous catheters inserted. Some patients had Fogarty catheter thrombectomies and interposition Great Saphenous Vein (GSV) graft repairs, while some others had successful takedown of the AVF, Fogarty thrombectomy and direct prolene 6/0 repair of the vein & arterial wall defects. All those that underwent surgical treatment had successful recovery. Conclusion: Femoral vein cannulation, apparently easy to perform, should not be used as the vascular access of choice for chronic haemodialysis.

Liquid-Driven Microinjection System for Precise Fundus Injection.

Microinjection is usually applied to the treatment of some retinal disorders, such as retinal vein cannulation and displaced submacular hemorrhage. Currently, the microinjection procedure is usually performed by using the viscous fluid control of a standard vitrectomy system, which applies a fixed air pressure through foot pedal activation. The injection process with the fixed pressure is uncontrollable and lacks feedback, the high flow rate of the injected drug may cause damage to the fundus tissue. In this paper, a liquid-driven microinjection system with a flow sensor is designed and developed specifically for fundus injection. In addition, a PID sliding mode control (SMC) method is proposed to achieve precise injection in the injection system. The experimental results of fundus simulation injection demonstrate that the microinjection system meets the requirements of fundus injection and reduces the impact of the injection process on the fundus tissue.

Comparison of ultrasound guided supraclavicular subclavian vein versus infraclavicular subclavian/axillary vein catheterization: A systematic review and meta analysis.

Subclavian vein cannulation is an important technique of central venous cannulation with a supraclavicular and an infraclavicular approach. There are randomized controlled trials (RCTs) which highlight the various differences between these two approaches when accessed via ultrasound. We undertook a meta-analysis to compare the ultrasound guided supraclavicular subclavian and the infraclavicular subclavian/axillary vein cannulation, keeping in mind that the infraclavicular approach may lead to cannulation of either subclavian/axillary vein. This meta-analysis encompassed studies that compared ultrasound-guided supraclavicular subclavian vein and infraclavicular subclavian/axillary vein. Binary outcomes were presented as odds ratios (OR), while continuous outcomes were presented as standardized mean differences (SMD) accompanied by 95% confidence intervals (95% CI). Potential trials meeting the eligibility criteria were sought from databases including PubMed, PubMed Central, The Cochrane Library, and EMBASE, covering the period from inception to April 30, 2023. The analysis comprised a total of six randomized controlled trials (RCTs) and one retrospective observational study collectively involving 1812 patients. The first pass success rate for subclavian vein catheterization was found to be greater with the supraclavicular approach (OR = 1.91 [95% CI 1.04-3.50]; p = 0.0002; I2 = 77%). Moreover, the supraclavicular approach exhibited a significantly shorter catheterization time compared to the infraclavicular approach (SMD = -0.26 [95% CI -0.54 to 0.03]; p = 0.003; I2 = 73%). Notably, there was no substantial disparity in complication rates between the two approaches (OR = 0.66 [95% CI 0.35-1.24]; p = 0.20; I2 = 0%). Ultrasound-guided supraclavicular approach for subclavian vein catheterization is superior to the infraclavicular approach for subclavian/axillary vein catheterization, with higher first-pass success rates, shorter catheterization times. However, there were no differences in the complication rates.

Axillary vein as an alternative venous access site for VV-ECMO cannulation: a case report

BackgroundUltrasound-guided percutaneous axillary vein cannulation can reduce cannulation failure and mechanical complications, is as safe and effective as internal jugular vein cannulation, and is superior to subclavian vein cannulation using landmark technique. As far, reports of venovenous extracorporeal membrane oxygenation (VV-ECMO) with percutaneous axillary vein cannulation are rare.Case presentationA 64-year-old man presenting with dyspnea and chest tightness after aspirating sewage was admitted to the emergency department. Computed tomography (CT) showed diffuse exudation of both lungs and arterial blood gas analysis showed an oxygenation index of 86. He was diagnosed with aspiration pneumonia-induced acute respiratory distress syndrome (ARDS) and intubated for deteriorated oxygenation. Despite the combination therapy of protective mechanical ventilation and prone position, the patient’s oxygenation deteriorated further, accompanied with multiple organ dysfunction syndrome, which indicated the requirement of support with VV-ECMO. However, vascular ultrasound detected multiple thrombus within bilateral internal jugular veins. As an alternative, right axillary vein was chosen as the access site of return cannula. Subsequently, femoral-axillary VV-ECMO was successfully implemented under the ultrasound guidance, and the patient’s oxygenation was significantly improved. Unfortunately, the patient died of hyperkalemia-induced ventricular fibrillation after 36 h of VV-ECMO running. Despite the poor prognosis, the blood flow during ECMO run was stable, and we observed no bleeding complication, vascular injury, or venous return disorder.ConclusionsAxillary vein is a feasible alternative access site of return cannula for VV-ECMO if internal jugular vein access were unavailable.

Anatomical review of internal jugular vein cannulation.

The internal jugular veins (IJV) are the primary venous outflow channels of the head and neck. The IJV is of clinical interest since it is often used for central venous access. This literature aims at presenting an overview of the anatomical variations, morphometrics based on various imaging modalities, cadaveric and surgical findings, and the clinical anatomy of IJV cannulation. Additionally, the anatomical basis of complications, techniques to avoid complications, and cannulation in special instances are also included in the review. The review was performed by a detailed literature search and review of relevant articles. A total of 141 articles were included and organized into anatomical variations, morphometrics, and clinical anatomy of IJV cannulation. The IJV is next to important structures such as the arteries, nerve plexus, and pleura, which puts them at risk of injury during cannulation. Anatomical variations such as duplications, fenestrations, agenesis, tributaries, and valves, may lead to an increased failure rate and complications during the procedure, if unnoticed. The morphometrics of IJV, such as the cross-sectional area, diameter, and distance from the skin-to-cavo-atrial junction may assist in choosing the appropriate cannulation techniques and hence reduce the incidence of complications. Age, gender, and side-related differences explained variations in the IJV-common carotid artery relationship, cross-sectional area, and diameter. Accurate knowledge of anatomical variations in special considerations such as paediatrics and obesity may help prevent complications and facilitate successful cannulation.

Comparison of the ultrasound-guided supraclavicular and infraclavicular approaches for subclavian vein cannulation in children with congenital heart disease

Objective(s)Central venous catheterization (CVC) is widely used in pediatric critical patients. We thought to compare the success rate and safety of ultrasound-guided subclavian vein cannulation performed via infraclavicular and supraclavicular approaches. DesignWe compared the success rate of the first puncture and other information for cannulation in the children with congenital heart disease (CHD) requiring central venous catheterization who were randomly assigned to the supraclavicular approach group (Group A) or infraclavicular approach group (Group B). SettingMedical university hospital pediatric cardiac intensive care units (CICUs). ParticipantsPediatric patients diagnosed with CHD in the preoperative period who were admitted to the CICU and required subclavian vein catheterization. InterventionsUltrasound-guided subclavian vein cannulation. Measurements & Main ResultsSixty-seven children were included in the study, with 32 in Group A and 35 in Group B. Notably, there was a significant difference in the success rate of the first puncture between Groups A and B (90.6% vs. 71.4, %, p = 0.047). Furthermore, the access time in Group A was 11.8 (3.2–95) seconds, which was significantly shorter than that in Group B (16.0 [6.5–227] seconds, p = 0.001). In addition, the catheter malposition rate in Group A was significantly lower than that in Group B (0% vs. 11.4%, p = 0.049). Conversely, there were no significant differences in the total access time, overall success rate, and complications (e.g., pneumothorax, hemorrhage, puncture artery, and nerve injury) between the two groups. ConclusionsFor children with congenital heart disease requiring central venous catheterization during the perioperative period, the subclavian vein is a feasible site for catheterization. The supraclavicular approach, especially the left side, has a higher first-puncture success rate, shorter access time, lower complications, and the trend of lower incidence of catheter malposition. However, a larger sample size of randomized controlled study is expected to verify the advantages of ultrasound-guided subclavian catheterization in children.

A Comparison of Techniques of Internal Jugular Vein Cannulation: Anatomical Landmark, Ultrasound Guided Pre-location, and Real-Time Ultrasound Guided.

The objective of our study is to compare the success rate, duration, and incidence of complications of a right internal jugular vein (IJV) cannulation by using three different techniques. A randomised controlled trial was conducted at atertiary care teaching hospital. A total of201 patients were randomly allocated to one of the following three groups (67 in each group). Techniques were categorised as anatomical landmark technique group (Group ALT), ultrasound guided pre-location group (Group USG-Pre), and real-time ultrasound-guided technique group (Group USG-RT). Central venous catheter insertion via three techniques. In 138 (73.01%) patients' IJV canulated in the first attempt, USG-RT, USG-Pre, and ALT were 51 (83.6%), 44 (72.1%), and 43 (64.2%), respectively. On the other hand, 37 (19.57%) patients were required in the second attempt, while only 14 (7.40%) patients were required in the third attempt for successful IJV cannulation. The success rates, as defined in our study, were only 138 (73%) as, in 51 (27%), we cannulated in more than a single attempt or switched to another technique. We found a significant difference in preparation time in all techniques as P-value <0.05, but no significant difference was found in venous access time, cannulation time, and duration of the procedure. Any technique can be used for IJV cannulation, but the most acceptable is the real-time US technique. However, no difference in the overall procedure time among all three techniques was noted, and no major incidence of complication was found.

The application of extracorporeal membrane oxygenation in emergent airway management - a single-center retrospective study

BackgroundEmergent airway occurrences pose a significant threat to patient life. Extracorporeal membrane oxygenation (ECMO) has been proven to be an effective method for managing emergent airways.MethodsA retrospective analysis was conducted on all patients receiving ECMO as an adjunct for emergent airway management from January 2018 to December 2022 at the People’s Hospital of Zhongshan City. We collected the basic information of the patients, their blood gas data before and after ECMO, the related parameters of ECMO, and the outcome and then analyzed and summarized these data.ResultsSix patients, with an average age of 51.0(28–66) years, received veno-venous (VV)- ECMO as an adjunct due to emergent airway issues. The average ECMO support duration was 30.5(11–48) hours. All six patients were successfully weaned off ECMO support, with five (83.3%) being successfully discharged after a hospital stay of 15.5(7–55) days. All six patients underwent VV-ECMO through femoral-internal jugular vein cannulation. Among these, five patients, whose airway obstruction was due to hemorrhage, underwent a non-anticoagulant ECMO strategy with no recorded thrombotic events.ConclusionsThe rapid establishment of ECMO support is aided by the establishment of a standardized ECMO initiation protocol and the formation of a multidisciplinary rapid-response ECMO team, which is particularly crucial for emergent airway management. When airway obstruction results from hemorrhagic factors, the early adoption of a non-anticoagulant ECMO strategy can be considered when implementing VV-ECMO.

Adrenal Vein Sampling: Does the Location of the Non-adrenal Venous Sample Matter?

PurposeAdrenal vein sampling (AVS) is used to lateralise and differentiate unilateral from bilateral aldosterone production in primary aldosteronism. The adrenal venous samples are standardised to a peripheral or low inferior vena cava (IVC) sample and compared. It is unknown whether the location of the non-adrenal sample affects the results. This study compares AVS results standardised to the low IVC and right external iliac vein (REIV).MethodsPatients who underwent AVS between March 2021 and May 2023 were included. All procedures were undertaken by a single operator (AA). Demographic data and AVS results were collected from patients’ electronic records. Catheterisation success and lateralisation were assessed using both low IVC and REIV samples. Equivalence test was used to compare the cortisol and aldosterone levels.ResultsEighty-one patients, (M: F = 38:43), aged between 29 and 74 were included. Bilateral successful adrenal vein cannulation was achieved in 79/81 (97.5%) cases. The mean cortisol levels from the REIV were statistically equivalent although there was a small and not biologically significant difference from the low IVC (respective geometric means 183 nmol/l vs. 185 nmol/l, p = 0.015). This small difference in cortisol may be due to accessory adrenal venous drainage into the IVC. The aldosterone and aldosterone/cortisol ratios were statistically equivalent. There was no discordance in selectivity or lateralisation when the IVC or REIV measurements were used.ConclusionThe IVC and REIV samples may be used interchangeably during AVS.Graphical

A Novel Approach for Simultaneous Venoarterial Extracorporeal Membrane Oxygenation and Left Ventricular Decompression Therapy With Impella (ECPella)

Percutaneously placed veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is commonly used to support patients with refractory cardiac arrhythmias or arrest and worsening cardiogenic shock (CS). Peripheral VA-ECMO by retrograde flow of blood in the aorta results in a significant increase in left ventricle (LV) afterload. A severely dysfunctional LV may be unable to overcome this afterload to open the aortic valve and unload itself. This may lead to LV distension, increased left ventricular pressure, poor coronary blood circulation, increased left atrial pressures, pulmonary edema, and pulmonary hypertension. Moreover, it jeopardizes ventricular recovery, particularly in the presence of ischemia-induced myocardial impairment. Furthermore, if the aortic valve remains closed during the cardiac cycle, stasis of blood in the LV and aortic root may increase the risk of thrombus formation. These complications may preclude cardiac recovery and the patient from being a heart transplant candidate. In patients with CS, utilizing Impella with VA-ECMO, commonly referred to as ECPella, has consistently been shown to reduce mortality and improve outcomes. Patients who need prolonged ECPella support as a bridge to recovery or transplant may remain bed-bound since ambulation of patients with two mechanical circulatory support devices is challenging. We present the technique of ECPella placement through Y chimney graft anastomosis on the axillary artery for arterial cannula and Impella insertion and percutaneous cannulation of the right internal Jugular vein for venous cannula. This technique gives the ease of ambulation and decannulation of VA-ECMO under local anesthesia without requiring intubation or a trip to the operating room.

Artificial Intelligence, Digital Imaging, and Robotics Technologies for Surgical Vitreoretinal Diseases

ObjectiveTo review recent technological advancement in imaging, surgical visualization, robotics technology and the use of artificial intelligence in surgical vitreoretinal (VR) diseases. BackgroundTechnological advancements in imaging enhance both pre-operative and intra-operative management of surgical VR diseases. Widefield imaging in fundal photography and optical coherence tomography (OCT) can improve assessment of peripheral retinal disorders like retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and non-invasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize three-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverages on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases. ConclusionThis review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care.

POCUS guided small saphenous vein cannulation: A novel approach for peripheral venous assess in prone position

Peripheral intravenous cannulation (PIVC) is a routine procedure in perioperative, and critical care settings and nearly one-third of the patients may have difficult intravenous access (DIVA). PIVC is challenging in a prone position in an intraoperative setting when there is a need for emergency access. Point of care ultrasonography (POCUS) is becoming the standard for assisting DIVA and improving the success rate. The small saphenous vein (SSV) in the posterolateral side of the mid-calf is a consistent vein in the lower extremity that provides an acceptable diameter and optimal depth for POCUS-guided PIVC in the prone position. A successful SSV cannulation was performed with an 18-G peripheral intravenous catheter under POCUS guidance on a 34-year-old male polytrauma patient in the prone position during the intraoperative period scheduled for D2 spine fixation. The SSV can be a credible option for emergency DIVA in the prone position under POCUS guidance.

Ultrasound-guided subclavian vein cannulation using open door technique - A technical report.

Ultrasound-guided subclavian vein cannulation using open door technique - A technical report.

Cerebral perfusion is elevated in a novel model of aged hAβKI APOE4 mice

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aβ Knock‐In (hAβKI) mouse carrying the APOE4 allele. APOE4 carriers are at increased risk for AD. Previous studies have demonstrated altered cerebrovascular integrity and function. We examined the cerebrovascular function in the hAβKI APOE4 mice at 18mo of age using perfusion‐weighted magnetic resonance imaging (PWI). We investigated brain‐wide perfusion alterations in conjunction with histopathological vessel painting.MethodsContrast‐enhanced PWI MRI (9.4T) was undertaken from hAβKI APOE4 (n = 6) and WT (n = 5) mice at 18mo of age following tail vein cannulation for Gadolinium infusion. Imaging sequences included: T1‐pre and post‐infusion, PWI (10min) and susceptibility‐weighted imaging (SWI) for blood extravasation and iron content. All data were processed using JIM v9 software for maps of cerebral blood flow (CBF), volumes (CBV), time to peak, mean transit time and dynamic susceptibility measures for blood‐brain barrier dysfunction. Manual regions of interest (ROI) were performed for cortex, temporal lobe cortex, dorsal hippocampus and thalamus, and semi‐automatic 30+ regions based on the Allen mouse brain atlas. At the end of the in vivo experiments all mice underwent vessel painting followed by microscopic analyses.ResultsCompared to WT mice at 18mo of age, hAβKI APOE4 mice exhibited elevated CBF in virtually all regions examined. CBF was elevated approx. 16%, 11%, 4% and 23% in the cortex, hippocampus, thalamus and temporal lobe cortex, respectively. CBF was significantly elevated in the retrosplenial and temporal lobe cortices (p&lt;0.05). CBV was also significantly increased in temporal lobe. Ongoing analyses will correlate vascular network measures (density, junctions, length) to PWI metrics as well as to hAβKI only mice.ConclusionsThe 18mo hAβKI APOE4 mouse compared to WT exhibited consistent brain‐wide elevations in cerebrovascular measures. This increase may represent a compensatory mechanism to maintain decreased metabolism that occurs with aging. The MODEL‐AD consortium (UCI/IUSM/JAX) continues to develop new and novel AD mouse models. All data will be made available to AD researchers via the Sage Knowledge Network (https://adknowledgeportal.synapse.org/).

Cerebral perfusion is elevated in a novel model of aged hAβKI APOE4 mice

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aß Knock‐In (hAßKI) mouse carrying the APOE4 allele. APOE4 carriers are at increased risk for AD. Previous studies have demonstrated altered cerebrovascular integrity and function. We examined the cerebrovascular function in the hAßKI APOE4 mice at 18mo of age using perfusion‐weighted magnetic resonance imaging (PWI). We investigated brain‐wide perfusion alterations in conjunction with histopathological vessel painting.MethodContrast‐enhanced PWI MRI (9.4T) was undertaken from hAßKI APOE4 (n = 6) and WT (n = 5) mice at 18mo of age following tail vein cannulation for Gadolinium infusion. Imaging sequences included: T1‐pre and post‐infusion, PWI (10min) and susceptibility‐weighted imaging (SWI) for blood extravasation and iron content. All data were processed using JIM v9 software for maps of cerebral blood flow (CBF), volumes (CBV), time to peak, mean transit time and dynamic susceptibility measures for blood‐brain barrier dysfunction. Manual regions of interest (ROI) were performed for cortex, temporal lobe cortex, dorsal hippocampus and thalamus, and semi‐automatic 30+ regions based on the Allen mouse brain atlas. At the end of the in vivo experiments all mice underwent vessel painting followed by microscopic analyses.ResultCompared to WT mice at 18mo of age, hAßKI APOE4 mice exhibited elevated CBF in virtually all regions examined. CBF was elevated approx. 16%, 11%, 4% and 23% in the cortex, hippocampus, thalamus and temporal lobe cortex, respectively. CBF was significantly elevated in the retrosplenial and temporal lobe cortices (p&lt;0.05). CBV was also significantly increased in temporal lobe. Ongoing analyses will correlate vascular network measures (density, junctions, length) to PWI metrics as well as to hAßKI only mice.ConclusionThe 18mo hAßKI APOE4 mouse compared to WT exhibited consistent brain‐wide elevations in cerebrovascular measures. This increase may represent a compensatory mechanism to maintain decreased metabolism that occurs with aging. The MODEL‐AD consortium (UCI/IUSM/JAX) continues to develop new and novel AD mouse models. All data will be made available to AD researchers via the Sage Knowledge Network (https://adknowledgeportal.synapse.org/).