Blood Flow Research Articles

Changes in brain connectivity and neurovascular dynamics during dexmedetomidine-induced loss of consciousness.

Understanding the neurophysiological changes that occur during loss and recovery of consciousness is a fundamental aim in neuroscience and has marked clinical relevance. Here, we utilize multimodal magnetic resonance neuroimaging to investigate changes in regional network connectivity and neurovascular dynamics as the brain transitions from wakefulness to dexmedetomidine-induced unconsciousness, and finally into early-stage recovery of consciousness. We observed widespread decreases in functional connectivity strength across the whole brain, and targeted increases in structure-function coupling (SFC) across select networks -- especially the cerebellum -- as individuals transitioned from wakefulness to hypnosis. We also observed robust decreases in cerebral blood flow (CBF) across the whole brain -- especially within the brainstem, thalamus, and cerebellum. Moreover, hypnosis was characterized by significant increases in the amplitude of low-frequency fluctuations (ALFF) of the resting-state blood oxygen level-dependent signal, localized within visual and somatomotor regions. Critically, when transitioning from hypnosis to the early stages of recovery, functional connectivity strength and SFC -- but not CBF -- started reverting towards their awake levels, even before behavioral arousal. By further testing for a relationship between connectivity and neurovascular alterations, we observed that during wakefulness, brain regions with higher ALFF displayed lower functional connectivity with the rest of the brain. During hypnosis, brain regions with higher ALFF displayed weaker coupling between structural and functional connectivity. Correspondingly, brain regions with stronger functional connectivity strength during wakefulness showed greater reductions in CBF with the onset of hypnosis. Earlier recovery of consciousness was associated with higher baseline (awake) levels of functional connectivity strength, CBF, and ALFF, as well as female sex. Across our findings, we also highlight the role of the cerebellum as a recurrent marker of connectivity and neurovascular changes between states of consciousness. Collectively, these results demonstrate that induction of, and emergence from dexmedetomidine-induced unconsciousness are characterized by widespread changes in connectivity and neurovascular dynamics.

Abstract 4143256: Non-invasive, Radiation-free, Non-contrast Myocardial Volume Oxygen Consumption Quantification Using Free-breathing MR Blood Oximetry

Background: Myocardial oxygen consumption (MVO 2 ) is a central marker in measuring cardiac energetics. Current methods to quantify MVO 2 are inaccessible due to the requirement of invasive procedures or PET agents that require onsite cyclotrons. Hypothesis A free-breathing, non-ECG-gated, motion-resolved Cardiac MR blood oximetry technique can noninvasively quantify MVO 2 in standard clinical MRI scanners without using ionizing radiation and contrast agents. Method: The developed free-breathing CMR imaging technique was prescribed in a 3T clinical scanner to the mid left ventricle (LV) and the cross-section of the coronary sinus(CS) slices of the heart to obtain the corresponding blood oxygenation (SbO 2 ) and the hematocrit (Hct) in heart chambers. 2D phase contrast CMR was performed in the CS to quantify the myocardial blood flow (MBF). The MVO 2 was quantified with Fick’s law (MVO 2 =arterio-venous oxygen difference x MBF). We examined the developed method in healthy pigs (N=7) under rest and adenosine stress and validated it against invasive blood sampling. In addition, we tested the method’s clinical feasibility in healthy human volunteers (N=4). Results: Comparable blood oxygenation levels (SbO 2 ) and MVO 2 were measured and compared between the non-invasive CMR and invasive ground truth (Fig. 1). Significantly increased coronary sinus SbO 2 is observed in both methods during adenosine infusion. It is accompanied by decreased MVO 2 and rate pressure product (RPP) (Rest: CMR=10.2±2.7ml/min, Inv.=10.8±6.9 ml/min, RPP=7956.9±620.9 mmHg/min; Stress: CMR=5.3±1.9 ml/min, Inv=6.3±3.6 ml/min, RPP=5338.2±618.3 mmHg/min). In Fig. 2, the healthy human volunteers' MVO 2 estimations(14.1±6.7ml/min) shows no statistical difference compared to the previous invasive measurements(16.5±4.8 ml/min, Ganz, et al. circulation 1971). Conclusions: The proposed noninvasive CMR technique can quantify MVO 2 in standard MRI scanners without using a needle. It has the potential to provide an accessible, risk-free assessment of myocardial metabolism for patients with potential metabolism impairments.

Abstract 4135289: Renal Blood Perfusion is Closely Related to Right Ventricular Volume Overload in Congestive Heart Failure

Background: Cardiorenal syndrome (CRS) involves a bidirectional relationship where dysfunction in one organ exacerbates the other. A key factor in this interaction is the impact of right ventricular (RV) volume overload on renal blood flow, which is vital for the progression and management of heart failure (HF). Objective: This study aims to explore and quantify the relationship between right ventricular volume overload, i.e, echocardiographic assessments of right ventricular diameter (RVD), and the time-to-peak (TTP) of renal blood flow in patients with HF measured by 99mTc-DTPA renal scintigraphy. Methods: This single-center study included 304 stable, ambulatory HF patients admitted between October 2017 and August 2022. HF was diagnosed based on the 2016 ESC guidelines. Echocardiographic parameters, including RVD, and TTP of renal blood flow measured by 99mTc-DTPA renal scintigraphy, were collected. Statistical analysis was conducted using SPSS and R software, with Spearman correlation analysis used to assess the relationship between echocardiographic parameters and TTP. Results: The study showed there was a significant correlation between RVD and TTP (rs=0.535, P <0.001), indicating that RV volume overload is closely related to impaired renal perfusion. The median TTP among the study population was 27.25 seconds (IQR: 21-39 seconds). Corrected for body surface area (BSA), RVD was found to be significantly higher in patients with heart failure with reduced ejection fraction (HFrEF) compared to heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) (HFrEF: 20.62 mm/m 2 , HFmrEF: 18.72 mm/m 2 , HFpEF: 18.09 mm/m 2 ; p < 0.001). Furthermore, right atrial diameter (RAD) corrected for BSA (RAD/BSA) demonstrated the strongest correlation with TTP in the HFrEF subgroup (rs=0.602, p<0.001). Conclusions: Our findings highlight the significant impact of right ventricular volume overload on renal perfusion, providing valuable insights into the pathophysiology of CRS. These results suggest that therapeutic strategies aimed at reducing RV overload could enhance renal perfusion and improve overall outcomes in HF patients.

Abstract 4136901: Mechanosensitive channel protein Piezo1 synergizes with TLR4 to enhance osteogenic responses in human aortic valve interstitial cells

Background: Calcific aortic valve disease (CAVD), a common heart valve disease in the elderly, has a complex pathogenesis. Abnormal blood flow shear can be regarded as an important factor in the development of CAVD, and a key molecule that responds to mechanical stress is the mechanosensitive ion channel protein Piezo1; however, the role of Piezo1 in CAVD has not been clarified. Methods and results: We collected CAVD patients and their age- and sex-matched controls, and compared the differences in the protein expression levels of Piezo1 and TLR4 between the two using Western blot and other techniques, and found that the expression of Piezo1 and TLR4 proteins was elevated in the CAVD group. We gave LPS or Piezo1 agonist Yoda1 to stimulate aortic valve mesenchymal stromal cells, respectively, and the Western blot results showed that ALP and Runx2 expression were elevated after LPS and Yoda1 stimulation, and immunofluorescence and alizarin red staining showed similar results. Inhibition of TLR4 or Piezo1 attenuated the osteogenic differentiation of AVICs. Cellular immunofluorescence results showed that TLR4 could be transported from the Golgi to the cell membrane under Yoda stimulation, and Golgi-cell membrane transport of TLR4 was attenuated after Rab3b knockdown by siRNA. After first pre-stimulation with Yoda1 and then stimulation with LPS, Western blot and immunofluorescence results showed that the protein levels of ALP and Runx2 as well as NF-κB phosphorylation were to be significantly increased. Conclusion: Stimulation of Piezo1 and TLR4 can enhance the osteogenic response of AVICs. Stimulation of Piezo1 enhances the transport of TLR4 from the Golgi to the cell membrane via Rab3b, and Piezo1 synergistically enhances the osteogenic response of AVICs with TLR4, thus promoting the development of CAVD.

Abstract 4137144: Return to Cath Lab: Chest Pain Resolution after Right Coronary Artery Chronic Total Occlusion Intervention

Introduction: Subacute stent thrombosis (ST) is related to high rates of cardiac reinfarction. We present a case of reinfarction from ST. The patient’s chest pain (CP) was not alleviated with initial revascularization of his left circumflex (LCx) ST, requiring PCI to his right coronary artery (RCA) chronic total occlusion (CTO). This is a novel approach to CTO PCI which is traditionally a non-urgent procedure. Case: A 53-year-old male with a history of coronary artery disease and surgical turndown presented to the ED with CP. Two weeks prior he had impella guided LM bifurcation PCI with DES and ramus intermedius (RI) angioplasty (PTA) but was nonadherent to clopidogrel. He had a BP of 127/85, HR of 65, and was on room air. Exam was unremarkable. His EKG was in sinus rhythm with S-T depressions ~1mm in leads V1-V4 concerning for posterior infarction. HS-troponin (HST) was 60. Angiography (CA) showed thrombotic occlusion of his LCx DES (Fig 1a) and an RCA CTO (Fig 1c). Optical coherence tomography (OCT) revealed DES struts overlying the ostial LCx concerning for mechanical deformation from carinal shift. OCT guided PTA and laser thrombectomy (LT) of the LCx led to TIMI-3 Flow. LT and kissing balloon inflation (BI) was performed on the LAD and LCx to reshape the carina. HST peaked at 116,012. He had CCS Class IV CP despite medical therapy and returned for re-look CA with TIMI-3 flow in the left-sided circulation without thrombus (Fig 1b). He had PCI to his distal RCA CTO with two DES and TIMI-3 flow in the RCA (Fig 1d). He did not have recurrence of CP. Discussion: Bifurcation PCI leads to challenges from anatomic reconfiguration, metallic DES deformity, and changes in blood flow leading to increased risk of distal ST. This patient’s CA demonstrated LM DES material overlying the LCx from carinal shifting which likely led to interrupted flow dynamics. His LCx ST was partly due to this stasis and his clopidogrel nonadherence. Despite PCI of his LCx his CP remained with poor collateral flow from the left circulation. While CTO procedures are typically done non urgently, emergent intervention on our patient’s RCA CTO led to complete resolution of his CP and clear benefit for symptomatic management.

Maternal Serum SCUBE-1: A Novel Ischemic Marker in Preeclampsia

Background: SCUBE-1 (Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-domain-containing protein 1) is a novel marker of ischemia, which is a cell surface-secreted protein in the platelets and endothelial cells. The aim of the study is to measure serum SCUBE-1 levels and investigate their association with uteroplacental blood flow in patients with preeclampsia. Methods: The study was conducted on patients with preeclampsia. Maternal serum SCUBE1 and IMA levels were the main outcomes. The control group consisted of gestational-age-matched pregnant women. Fetal umbilical artery (UA) pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio (CPR), and maternal uterine artery (UtA)-PI were also examined, and correlation analysis was performed to reveal the association between maternal serum SCUBE1 levels and Doppler findings. Results: The study group consisted of thirty-two preeclamptic patients, and the control group consisted of thirty-two uncomplicated singleton pregnancies. Maternal serum SCUBE1 and IMA levels were significantly higher in preeclamptic women compared to the control group (p < 0.000, p < 0.004, respectively). Mean UtA-PI values and fetal UA-PI values were significantly higher in preeclamptic pregnant women compared to the control group (p < 0.05, p < 0.05, respectively). However, the average CPR was significantly lower in pregnant women with preeclampsia (p < 0.05). While no significant correlation was found between maternal serum SCUBE1 levels and UA-PI and CPR (p > 0.05, p > 0.05, respectively), a significant correlation was found between right and left UtA-PI (p < 0.004, p < 0.006, respectively). Conclusions: The maternal serum SCUBE1 level is increased in patients with preeclampsia, and this increase is significantly correlated with the maternal uterine artery pulsatility index.

Abstract 4117646: The Ultimate Test in Hemocompatibility: HeartMate3 Restart After Prolonged Pump Shut Down

Introduction: The HeartMate 3 (HM3) LVAD, was shown to have a higher survival free of hemocompatibility related adverse events (HRAE) compared to its predecessors (HM2, HVAD). Superior HM3 outcomes are attributed to wide blood flow pathways coupled with frictionless movement and intrinsic pulsatility, reducing shear stress and blood stasis. It is unknown if improved hemocompatibility can withstand pump restart after prolonged shutdown. We herein report a case of HM3 pump stoppage without subsequent HRAE. Case Presentation: A 41-year-old male underwent HVAD implant in 2019 for advanced non-ischemic cardiomyopathy. This was exchanged to HM3 for recurrent neurological events despite therapeutic anticoagulation. Ten months after exchange, he awakened one morning to find his LVAD had been off for an unknown period but had not heard any device alarms (85dB if on battery power, 165dB if on wall power). Since he felt well he changed to battery power resulting in immediate pump restart. Log file analysis showed pump stoppage 2 am – 10 am, without preceding low flow alarms or power elevations. Management and Outcomes: In the ER INR was 1.5 (2.8 one week prior) and systemic heparin was started. Evaluation included: 1) CT brain without acute infarcts 2) echocardiogram without intracardiac thrombus 3) CT Angiography with patency of the inflow cannula and outflow graft 4) stable serial LDH measurements. The controller was exchanged, and analysis noted normal function. 1-year later the patient is maintained on warfarin and aspirin 325mg without further HRAE. Given the patient’s neurologic history and pump stoppage event, we did not invoke ARIES trial guidance and thus continued aspirin. Conclusion: Pump stoppage occurs when there is complete battery depletion, disconnection of both power leads, or the percutaneous lead from system controller. Our case is unique in that the duration of pump shutdown was 8 hours and INR subtherapeutic, without HRAE in the background of neurologic events on HVAD support. It has been previously reported that complete outflow graft thrombosis can occur shortly after LVAD decommissioning. The HM3 User Manual recommends restarting the pump immediately if off for a few minutes and using clinical judgment for longer durations due to increased risk for thromboembolic events. Our case adds to the paucity of existing data on improved hemocompatibility of the HM3 during rare circumstances of the ultimate test in hemocompatibility: complete pump shut down.

Abstract 4113951: Calcification Alters Luminal Surface Complexity in Cadaveric Left Anterior Descending Arteries

Background: Understanding the intricacies of luminal surface topographic changes in pathologic coronary arteries may yield insight not only on the efficacy of existing clinical interventions (e.g. impact of surface changes on stent anchoring), but also on the subsequent hemodynamic changes and pathophysiology of thrombus formation. In this study, we aim to detect and quantify luminal surface alterations induced by the presence of calcification in cadaveric left anterior descending arteries (LADs) using a novel approach–surface metrology. Methods: LADs (n=10) were harvested from cadaveric hearts using a systematic dissection approach, scanned using the Bruker Skyscan 1173 microCT scanner, and then underwent threshold-based image segmentation on Dragonfly by Object Research Systems to quantify the total calcium volume present throughout the vessel. Each specimen was then splayed open and up to 15 scans were performed at 20X magnification using the Sensofar S Neox optical profiler. Each scan subsequently underwent surface metrologic scale-sensitive fractal analyses in SensoMap 10. Results: Extent of calcification was standardized and expressed using the following ratio: total calcium volume by total vessel length (TC/VL). We considered a TC/VL ratio of 0-0.25 as low calcification and 0.26-0.5 as high calcification. Interestingly, our findings demonstrated statistically significant increases in smooth-rough crossover (SRC) and scale of maximum complexity (Smfc) with positive correlation, but reductions in fractal complexity (Lsfc) and fractal dimension (Dls) with negative correlation, in highly calcified compared to lowly calcified LADs. Conclusions: Our data suggests that the presence of calcium in the walls of LADs may translate to increased roughness in luminal surfaces generally, but smoothness over calcified plaques, locally. Our proposed mechanism is increased endothelial tension directly over areas of calcification, thus reducing surface complexity. Future studies will involve modeling blood flow using smooth particle hemodynamics (SPH) based on complete luminal and surface topographical geometries to evaluate the impact of these surface changes on hemodynamics.

Abstract 4124293: Exercise Capacity in Patients with Fontan Physiology

Introduction/Background: In the absence of a sub-pulmonary ventricle in the Fontan circulation, augmentation of pulmonary blood flow and filling of the systemic ventricle during exercise are limited. Cardiopulmonary exercise testing (CPET) is a reliable method for evaluation of aerobic capacity, gas exchange, and other physiologic parameters used for risk stratification in this population. Despite the ubiquitous use of CPET, reference ranges for patients with Fontan physiology are limited. The purpose of this study is to describe exercise characteristics and their relationship with different characteristics of Fontan physiology, imaging, and hemodynamics. Methods/Approach: In this retrospective cohort study, CPET results were reviewed for adult Fontan patients at the University of Washington between May 2021 and February 2024. Demographics, comorbidities, medications, type of Fontan conduit, imaging characteristics, hemodynamics, and exercise characteristics were included. Results were compared to a large previously published cohort of Fontan patients. Univariate linear regression was used to identify associations between demographics, cardiac anatomy, and exercise parameters. A p-value of less than 0.05 was considered statistically significant. Results/Data: Baseline demographics were notable for an older patient population (31±7 years) with lower indexed peak VO 2 (20.5±5.6 mL/kg/min) and greater V E /VCO 2 slope (37±7) compared to the historic cohort. Indexed peak VO2 was associated with age, BMI, type of Fontan conduit, FEV1, FVC, resting oxygen saturation, peak systolic blood pressure, and peak heart rate. Indexed peak VO 2 was notably not significantly associated with sex, systemic ventricular morphology, ventricular systolic function, Fontan pressure, or the presence of conventional heart failure medical therapy. Conclusions: In the growing population of older patients with Fontan physiology, development of age-specific population normative data may increase the clinical utility of CPET. Further investigation of the relationship between imaging characteristics, hemodynamics, and exercise parameters is needed in the Fontan population.

Correlation between antihypertensive drugs and cerebral hemodynamic parameters: insights from observational findings using transcranial Doppler.

Antihypertensives (AHD) can influence cerebral autoregulation (CA) and attenuate hypertrophic concentric remodelling of arterioles. The aim of this study was to examine the associations between AHD, CA and structural and functional properties of cerebral arteries. In this observational, cross-sectional study 115 volunteers were divided in group 1 (non-hypertensive) [n = 30]; group 2 (hypertensive with systolic blood pressure [SBP] < 140 and diastolic blood pressure [DBP] < 90 mmHg) [n = 54]; group 3 (hypertensive with SBP ≥ 140 or DBP ≥ 90 mmHg) [n = 31] and simultaneous measurements of systemic blood pressure (BP) and middle cerebral artery blood flow velocity (CBFV) were obtained from digital plethysmography and transcranial Doppler. Beat-to-beat, critical closing pressure (CrCP), resistance-area product (RAP) and autoregulation index (ARI) values were extracted by linear regression analysis of instantaneous BP and CBFV waveforms using computerised analysis. Pulsatility index (PI) was calculated and CO2 reactivity was assessed by the breath-holding test. Despite their higher RAP (1.7 [±0.7], p < 0.001) compared to groups 1 and 2, uncontrolled hypertensive using diuretics (p = 0.047) and α2-agonists (p = 0.009) had significantly lower PI. Impaired CO2 reactivity was common between the two hypertensive groups (p = 0.008), however ARI, CrCP and CBFV did not differ between them and non-hypertensive individuals and also did not correlate with any AHD used. Unlike the RAP, PI does not seem to reflect the real cerebrovascular resistence resulting from chronic arterial remodelling. Despite impaired CO2 reactivity, hypertensivehavearterial tonus and CA comparable to non-hypertensive. Experimental studies involving an untreated hypertensive control group are required to robustly make definitive conclusions about these questions.

Abstract 4147602: The Paradox Role of Sirtuin 6 In Coronary Microvascular Function under Metabolic Stress

Coronary microvascular dysfunction (CMD), which is associated with diabetic cardiomyopathy, Takotsubo cardiomyopathy, andheart failure with preserved ejection fraction (HFpEF), is understudied. CMD is characterized by impaired endothelial-dependent vasodilation, but detailed mechanisms have yet to be elucidated. Nuclear Sirtuin 6 (SIRT6) plays essential roles in gene transcriptional, stress tolerance, DNA repair, inflammation, and aging. SIRT6 is strongly associated with cardiovascular pathologies, but how SIRT6 regulates endothelial metabolisms and homeostasis under metabolic stress and the underlying mechanism remains poorly understood. It might be because global Sirt6 knockout mice are perinatally lethal caused by hypoglycemia, suggesting the essential role of SIRT6 in glucose metabolism. In our preliminary studies, we generated inducible global Sirt6 knockout mice by crossing with Sirt6 f/f mice with CAG-cre (Sirt6 f/f, CAG ), and mice were viable with normal glucose levels. However, they showed impaired endothelial-dependent dilation (EDD) and impaired coronary flow reserve (CFR), an index clinically used to diagnose CMD. It suggests that deletion of Sirt6 might cause EC dysfunction because Sirt6 is reported to protect EC from premature senescence and oxidative stress by sustaining high eNOS levels. Surprisingly, when we studied non-inducible Sirt6 endothelial-specific knockout (Sirt6 f/f, tie-2 cre ) and inducible Sirt6 endothelial-specific knockout (Sirt6 f/f, Cdh5-cre/ERT2 ) and wild-type (WT) mice, Sirt6 f/f, Tie-2 and Sirt6 f/f, Cadh5 mice do not phenocopy the inducible global SIRT6 knockout mice, they had normal EDD and CFR. When the mice were fed a high fat and high sugar (HFHS) diet, the Sirt6 f/f, Tie-2 and Sirt6 f/f, Cadh5 had impaired EDD, suggesting Sirt 6 functioned differently in the mice fed with chow diet or HFHS diet. We hypothesize Sirt 6 deficiency causes coronary endothelial dysfunction and contributes to CMD; activating Sirt6 will ameliorate CMD. EDD was assessed using myography (DMT). Myocardial blood flow (MBF) was measured by Doppler. Our preliminary data show that the mediator of coronary vasodilation switched from NO to H 2 O 2 in the Sirt6 knockout mice with impaired EDD. Interestingly, when the mice fed on HFHS were treated with Sirt 6 activator MDL-800, the coronary microvascular function was improved, and the blood glucose level was decreased. The underlying mechanism and the pathways involved will be elucidated.

Abstract 4135333: Peripheral Perfusion Index: Normative Values From Electronically Reported Critical Congenital Heart Disease Screenin

Background: Critical Congenital Heart Disease (CCHD) screening is performed in an effort to reduce morbidity and mortality associated with CCHD by facilitating early detection. This screening consists of pulse oximetry and is most effective at identification of cyanotic cardiac lesions, with less sensitivity for left sided obstructive lesions. Research: Question Peripheral perfusion index (PPI) is obtained from the plethysmographic signal of a pulse oximeter and represents the ratio of pulsatile to non-pulsatile blood flow. As such, it is a surrogate for peripheral perfusion at the site of measurement. PPI has been postulated to be an adjunctive screening method for low perfusion states in neonates, including left sided obstructive lesions. To date, reference ranges of PPI values in neonates have not been published in the United States. This project utilized electronically reported CCHD screening results to establish normative PPI data in healthy neonates. Methods: In Minnesota, CCHD screening results are electronically sent to the Minnesota Department of Health (MDH) and are cross referenced against the Minnesota Birth Information System, which tracks infants who are identified to have a congenital birth defect within the first year of life. These data were provided by the MDH for infants born in Minnesota from Jan 2017 through Dec 2022. Infants were included in the analysis if they did not have a known critical congenital heart defect, were born between 35 and 42 weeks gestation, and were 24-48 hours of life at time of screening. Results: PPI data from 11,179 cases were included in the analysis. Overall, there is a trend towards increasing PPI with gestational age. Pre-ductal PPI trended higher than post-ductal PPI. There was no difference between PPI in males and females. Conclusions: These data reflect trends identified in international data. This is the largest dataset to date of PPI in healthy neonates and the first in the United States. Future studies will compare neonates with left sided obstructive lesions against these normative data. If PPI is found to predict left sided obstructive lesions in neonates, there may be utility in use of PPI in CCHD screening to facilitate earlier detection of these lesions.

Abstract 4124084: Nitric Oxide Releasing Bionanomatrix Gel For Dialysis Arteriovenous Fistula Maturation

Introduction: About 600,000 patients in the US suffer from end-stage renal disease (ESRD); more than 75% of ESRD patients undergo dialysis. Vascular access dysfunction is a major cause of morbidity and hospitalization in dialysis patients. Arteriovenous fistulas (AVFs) are considered the gold standard of vascular access for dialysis. However, about 60% of AVFs fail to mature because of early venous neointimal development and poor vasodilation and vascular wall remodeling. Therefore, to promote AVF maturation, we propose the application of a nitric oxide (NO) releasing nanomatrix gel, or ‘NO gel’, on the created AVF. The NO gel is composed of peptide amphiphiles (PA), which contain a polylysine (KKKKK) group to form NO-donating residues. In this study, we test our hypothesis that the NO gel applied at AVF can promote AVF maturation by decreasing venous intimal hyperplasia, enhancing vasodilation and vascular outward remodeling in porcine model. Materials and Methods: PA containing with KKKKK was synthesized and charged with NO to produce NO gel. For in vivo studies, AVFs in porcine were created by connecting the jugular vein and carotid artery. The NO gel was applied perivascularly over the AVF anastomosis. And the pigs were sacrifice after 35 days. AVF hemodynamics were evaluated using MRI-based computed fluid dynamics analysis. Results: We found significant decrease in neointimal hyperplasia in porcine AVFs treated with NO gel compared to the control groups. Additionally, the percentage of open lumens was significantly higher in the NO gel-treated group. It is indicated that veins in NO treated group showed less fibrosis as an less type I collagen I produced in the NO treated group than control. Also, the NO gel significantly improved hemodynamics and vascular remodeling of porcine AVFs compared to the control. Conclusion: These results suggest that the NO gel plays a crucial role in AVF maturation by reducing intimal hyperplasia and stenosis following AVF creation in a pig model. When intimal hyperplasia is reduced and the vessel is dilated, less tensile force of blood flow is applied on the arterialized vein, directing the AVF to appropriate maturation.

Abstract 4131412: Effects of Angiotensin Converting Enzyme Inhibition And Afterload Reduction in Single Ventricle Patients Prior To Fontan: Not What You Might Think

Introduction: Pts with single ventricle (SV) after bidirectional Glenn (BDG) are placed on angiotensin converting enzyme inhibitors (ACEI) to reduce afterload, improve ventricular performance and allow for decreased systemic to pulmonary collateral flow (APC). No large scale data exists to support ACEI use in BDG pts to accomplish this. We hypothesized that ACEI may not perform as predicted. Goals: To determine if ACEI use in BDG pts decreases APC and improves ventricular function. Methods: Single center retrospective study of all BDG pts who underwent cardiac magnetic resonance (CMR) from 2010 to present. Demographics, medication, ventricular function and flow data were collected. Pts included were &gt;1 year old and on ACEI for &gt;3 months prior to CMR. Wilcoxon and Fisher Exact tests were used. Significance P&lt;0.05 Results: Of the 320 BDG pts (median 2.8 years old) studied, 137 (43%) were treated with ACEI. See table for all data. There was no difference in age, sex, medications (except for ACEI) or body surface area (BSA) between both groups. APC as a % of aortic flow and APC/BSA were not different between those treated with ACEI compared to those who were not, whether right (RV) or left ventricle (LV) dominant. There was no correlation of APC with time on ACEI or ACEI dosage. Ejection fraction (EF) was lower and end-diastolic volume (EDV) was higher in BDG on ACEI for the entire group and RVs. Although LV EDV was higher with those on ACEI, LV EF was the same for those on ACEI and those who weren’t (graph). APC as a % of aortic flow and APC/BSA positively correlated with EDV (rho 0.25-0.34, P&lt;.001). There was no difference in atrioventricular valve regurgitation between those on ACEI and those who were not (median 5 vs 6% respectively). As a surrogate for cerebral blood flow (CBF), superior vena caval (SVC) flow was lower for those on ACEI compared to those who were not. Conclusion: BDG pts treated with ACEI did not demonstrate decreased APC or improved ventricular performance. There is a suggestion that ventricular performance may be worse on ACEI. CBF is decreased in BDG on ACEI using SVC flow as a surrogate. This suggests that ACEI use in SV pts at the BDG stage is not indicated and should be discouraged.

Effect of left colonic artery preservation on perfusion at the anastomosis in rectal cancer surgery evaluated with intraoperative ultrasound.

Intraoperative ultrasound was used to assess the flow velocity in the marginal vessel arch adjacent to the anastomosis, critical for evaluating the anastomotic blood supply. This technique also enabled us to investigate the potential effects of preserving the left colonic artery on the perfusion of the anastomosis. This prospective study included 40 rectal cancer patients who underwent laparoscopic anterior resection between January 2021 and January 2023. The length of the inferior mesenteric artery (IMA) was measured from its origin to the first branch, and the diameters of the mesenteric vessel IMA, left colonic artery (LCA), and marginal mesenteric artery (MMA) were recorded. Blood flow velocity and Doppler ultrasound waveforms of the MMA near the anastomosis were collected. Measurements were taken both before and after clamping the IMA using atraumatic forceps. The tardus parvus pattern of the MMA ultrasound waveforms was recorded to evaluate the hypoperfusion status of the anastomosis. The mean velocities of MMA were 47.9cm/s before clamping and 34.9cm/s after atraumatic clamping, indicating significant differences (p < 0.05). Thirteen patients (32.5%) exhibited a Tardus parvus pattern after IMA atraumatic clamping. Multivariate analysis revealed older age and LCA diameter as independent clinical predictors of the hypoperfusion status after IMA clamping. Preservation of the LCA may improve perfusion near the anastomosis during rectal cancer surgery. Older age and LCA diameter can be considered useful predictors of the mesenteric hypoperfusion status after IMA ligation. Intraoperative ultrasound can evaluate the perfusion of the MMA near the anastomosis. Chinese Clinical Trial Registry-Registration number: ChiCTR2000041475.

ABCs of base therapy in neonatology: role of acetate, bicarbonate, citrate and lactate.

Metabolic acidosis is common in preterm and term newborn infants and may be attributed to a variety of etiologies, potentially requiring base therapy such as acetate or bicarbonate. However, concerns exist regarding potential harm of sodium bicarbonate due to intracellular acidosis, fluctuations in cerebral blood flow, and osmolar load with rapid infusions, with no improvement in survival when used during resuscitation. Alternative approaches to correct metabolic acidosis include the addition of acetate in parenteral nutrition, intravenous lactated Ringer's (LR) solution, and use of oral citrate. Current guidelines focus on addressing the underlying cause of acidosis, reserving the use of sodium bicarbonate (NaHCO3) for severe cases requiring acute correction, LR instead of saline for volume boluses and using acetate or citrate for slow correction to stabilize acid-base status. Further research is necessary to better understand the efficacy and safety of acetate, NaHCO3, and other base sources in treating metabolic acidosis in neonates.

Abstract 4136290: Toward Quantitative Assessment of Cerebrovascular Autoregulation in Neonates using Ultrafast Ultrasound Power Doppler

Introduction: Newborns with congenital heart diseases requiring cardiopulmonary bypass are at risk of neurodevelopmental impairment. The impact of deep hypothermia during cardiopulmonary bypass (DH-CPB) on cerebrovascular autoregulation (CAR) that controls brain perfusion in the presence of variable blood pressure is not well understood. Recently, Ultrafast Power Doppler (UPD) showed potential to study CAR in neonates based on the measurement of cerebral blood volume (CBV). However, since CAR relies mainly on the arterial vasoconstriction/vasodilation, the interpretation of brain perfusion based on CBV requires further separation of arterial CBV from total CBV. This study aims to use UPD to monitor CAR during DH-CPB in neonates. Methods: An ultrasonic probe (5.7 MHz) was placed on the anterior fontanel of 6 newborns before, during and after DH-CPB. Using ultrafast sequences generated by a Verasonic Vantage research system, mid-coronal plane images were acquired (PRF of 9 kHz, 5 compounded diverging waves). An adaptive spatiotemporal singular value decomposition was used to separate the blood signal from tissue signal and obtain UPD. CBV was computed in the deep gray matter (DGM). This region was chosen due to its higher susceptibility to hypoxic-ischemic injury. Arterial CBV was isolated from total CBV based on the upward arterial flow obtained using signed-power Doppler (See Fig A). Pearson correlation ® was computed between mean arterial blood pressure (MAP) and arterial CBV to study CAR. Results: Before and after DH-CPB, negative correlations were found between arterial CBV and MAP: -0.30 and -0.43 respectively. This indicates that an increase in MAP is associated with a decrease in cerebral arterial blood volume. This decrease in arterial CBV likely arises from arterial vasoconstriction, suggesting an active CAR response. Conversely, during DH-CPB, no correlation was found (r = -0.02). This means that despite the increase in MAP, arterial CBV remains unchanged. This lack of variation of arterial CBV is likely due to absent arterial vasoconstriction, suggesting an impaired CAR response. Conclusion: Our findings highlight the potential of UPD for continuous monitoring of CAR, paving the way for improving neurovascular management strategies during DH- CPB.

Abstract 4137257: Hepatocyte growth factor -mediated Angiogenesis supersession in Hyperhomocysteinemia

Background: Homocysteine (Hcy) is a well-established cardiovascular risk factor. Elevated homocysteine, or hyperhomocysteinemia (HHcy), inhibit the growth of endothelial cells and stimulate vascular smooth muscle cell proliferation. However, the mechanisms of HHcy disrupts angiogenesis remain unclear. Here we examine the molecular pathways involved in HHcy-impaired angiogenesis. Method: We generated Tg-hCBS+ Cbs-/- mice by crossing Cbs knockout mice and Tg-hCBS mice where human CBS cDNA was regulated by a zinc-inducible metallothionein promoter. The model exhibited severe HHcy (＞115 μmol/L). We conducted both in vivo and in vitro experiments, including vasculogenesis assays of retinal and heart tissues, aortic ring assay, and tube formation. Retinas were stained with Isolectin B4 and imaged using a confocal microscope. The Human Angiogenesis RT 2 Profiler™ PCR Array was used to profile 84 key angiogenesis-related genes. Homocysteine metabolites in Cbs mice were measured by HPLC. ChIP-seq data were analyzed using Chip Atlas. Additionally, 91 patients went through coronary angiography were enrolled from the Second Affiliated Hospital of Nanchang University. Participants with CTFC, greater than 27 frames per second were identified as having slow coronary arteries flow (SCF). Results: HHcy caused SCF in patients and impaired vasculogenesis in the retinas of newborn and 12-week-old Tg-hCBS Cbs-/- mice. Capillary density in the hearts of adult Tg-hCBS Cbs-/- mice was reduced. HHcy suppressed tube formation and aortic ring microvessel growth in a concentration-dependent manner. The PCR array revealed significant gene expression changes in Hcy treated human aortic endothelial cells. Notably, genes encoding hepatocyte growth factor (HGF), collagen type IV alpha 3, epiregulin, interferons, and leukocyte cell-derived chemotaxin 1 were downregulated by at least four-fold. In an acute myocardial infarction model, HGF expression was further reduced, and HGF treatment rescued Hcy-inhibited tube formation and microvessel growth. Hcy and S-adenosylhomocysteine levels were negatively correlated with plasma HGF levels. ChIP-seq data identified homocysteine-responsive hypomethylation in ETF, TFII, FOXP3, RXRa, and c-Jun Hcy-hypomethylation Box (-2701/0). Conclusion: HHcy impair angiogenesis via HGF inhibition, which has a rescue effect. Hypomethylation caused by Hcy affects the methylation status of specific CpG sites within the Hcy-hypomethylation box of the HGF gene.

Insights from Computational Fluid Dynamics and In Vitro Studies for Stent Protrusion in Iliac Vein: How Far Shall We Go?

These findings provide significant implications for the enhancement of iliac vein stent implantation strategies and stent design. The prevalent use of stents for treating Iliac Vein Compression Syndrome (IVCS) has shown efficacy, yet the associated clinical adverse events, including stent restenosis and postoperative thrombosis, are significant concerns. Up to now, the mechanism how the stent implantation induces the restenosis and DVT is still unclear. Our study hypothesizes that these adverse outcomes arise from altered blood flow dynamics following stent implantation. Employing computational modeling and medical imaging, we simulated IVCS after various stenting procedures to assess their impact on venous blood flow characteristics, including wall shear stress (WSS), residence time (RRT), and oscillatory shear index (OSI). Our findings reveal that a stent protruding into the vena cava impedes blood circulation, with increased protrusion exacerbating this obstruction. This is particularly evident at the vein bifurcation, where low WSS and elevated OSI and RRT are observed. Moreover, a higher stent strut density further obstructs blood flow, deteriorating the hemodynamic environment. Consequently, stent protrusion into the vena cava can enhance the likelihood of adverse post-surgical events. These insights have profound implications for optimizing iliac vein stent implantation techniques and stent design.

Blood flow-induced angiocrine signals promote organ growth and regeneration.

Recently, we identified myeloid-derived growth factor (MYDGF) as a blood flow-induced angiocrine signal that promotes human and mouse hepatocyte proliferation and survival. Here, we review literature reporting changes in blood flow after partial organ resection in theliver, lung, and kidney, and we describe the angiocrine signals released by endothelial cells (ECs) upon blood flow alterations in these organs. While hepatocyte growth factor (HGF) and MYDGF are important angiocrine signals for liver regeneration, by now, angiocrine signals have also been reported to stimulate hyperplasia and/or hypertrophy during theregeneration of lungs and kidneys. In addition, angiocrine signals play a critical role in tumor growth. Understanding the mechano-elastic properties and flow-mediated alterations in the organ-specific microvasculature is crucial for therapeutic approaches to maintain organ health and initiate organ renewal.