Hemodynamic Changes Research Articles

Hemorrhage Magnitude Correlates with Sympathetic Vasomotion in Conscious Rabbits

Each year, over 1.8 million people die from hemorrhagic shock, and the median time from onset to death is only two hours, making early recognition and prompt action the cornerstone of management. The sympathetic nervous system is the most rapid physiological hemodynamic compensatory mechanism, and we have developed a novel measure of sympathetic vascular control called sympathetic vasomotion which could serve as an early marker of hemorrhage. We performed unilateral renal denervation on six rabbits and instrumented these rabbits with bilateral renal flow probes and arterial pressure telemeters to allow for measurement of sympathetic vasomotion. After a two-week recovery period, the rabbits then underwent controlled blood withdrawal via an auricular arterial catheter. The differences in admittance gain and phase shift occurrence between the innervated and denervated kidneys increased significantly before any other hemodynamic changes. Over the first 15 minutes of hemorrhage, the differences in admittance gain and phase shift correlated with hemorrhage magnitude (r = 0.69 and 0.63, respectively), whereas the differences in coherence did not. The sum of the admittance gain and phase shift differences showed a slightly higher correlation with hemorrhage magnitude (r = 0.71). This data suggests that some features of sympathetic vasomotion may be useful as a biomarker for diagnosing early-stage normotensive hemorrhage and assessing treatment response. Further studies are needed to evaluate the utility of sympathetic nervous system monitoring in clinical contexts. Supported by NIH P01 HL62222 and NIH F30 HL118974. 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.

Abstract 2074: De Novo Nucleotide Synthesis Is Necessary For DNA Damage And Repair In Atheroprone Endothelial Cells

Aims: Endothelial cell (EC) metabolism is tightly regulated by hemodynamic changes to protect them from atherogenic injury induced by disturbed flow (d-flow) and other atherogenic risk factors. Therefore, characterizing the role of flow-induced metabolic reprogramming is important to develop new treatments for atherosclerosis and similar diseases. Currently, the effect of proatherogenic d-flow on EC nucleotide metabolism, including de novo purine and pyrimidine synthesis, remains under explored. ATIC and CAD are critical enzymes for de novo purine synthesis and pyrimidine synthesis, respectively. We investigated in the role of ATIC and CAD-mediated de novo nucleotide metabolism in atheroprone ECs. Methods and Results: (i) scRNA-Seq analysis results showed that DNA damage response was increased in ECs exposed to d-flow, this was accompanied by increased ATIC-mediated de novo purine synthesis and CAD-mediated de novo pyrimidine synthesis; (ii) Knockdown of ATIC or CAD with siRNA aggravated EC DNA damage, apoptosis and EC permeability induced by d-flow or other atherogenic factors; (iii) Supplement of nucleobases can rescue ATIC KD-mediated DNA damage and apoptosis in ECs; (iv) MYC, predicted high stringency binding with ATIC promoter, was highly expressed in d-flow induced ECs and MYC knockdown reduced the increased ATIC expression in d-flow induced ECs; (v) The atherosclerotic lesion size was markedly increased in EC-specific Atic deficient mice in atherosclerosis. Conclusion: ATIC and CAD-mediated de novo nucleotide synthesis in ECs supply nucleotides to repair DNA damage and preserve EC barrier integrity in vulnerable atheroprone regions and ultimately protect against the development and progression of atherosclerosis.

EGFR-mediated crosstalk between vascular endothelial cells and hepatocytes promotes Piezo1-dependent liver regeneration

Hepatocyte proliferation is essential for recovering liver function after injury. In liver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascular endothelial cells (VECs) to secrete large amounts of cytokines that enhance hepatocyte proliferation and play a pivotal role in liver regeneration. Piezo1, a critical mechanosensory ion channel, can detect and convert mechanical forces into chemical signals, importing external stimuli into cells and triggering downstream biological effects. However, the precise role of Piezo1 in VECs, especially in terms of mediating liver regeneration, remains unclear. Here, we report on a potential mechanism by which early changes in hepatic portal hemodynamics activate Piezo1 in VECs to promote hepatocyte proliferation during the process of liver regeneration induced by portal vein ligation in rats. In this liver regeneration model, hepatocyte proliferation is mainly distributed in zone 1 and zone 2 of liver lobules at 24–48 h after surgery, while only a small number of Ki67-positive hepatocytes were observed in zone 3. Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs via the PKC/ERK1/2 axis, further activating epidermal growth factor receptor (EGFR) and ERK1/2 signals in hepatocytes and promoting proliferation. In addition, cytokines secreted by Piezo1-activated VECs can induce hepatocytes to undergo epithelial–mesenchymal transition. In the liver lobules, the expression of EGFR in hepatocytes of zone 1 and zone 2 is significantly higher than that in zone 3. The EGFR inhibitor gefitinib inhibits liver regeneration by suppressing the proliferation of hepatocytes in the middle zone. Thus, activation of Piezo1 in VECs promotes hepatocyte proliferation, suggesting mechanical stimulation regulates hepatocyte proliferation in zone 1 and zone 2 during portal vein ligation-induced liver regeneration. These data provide a theoretical basis for the regulation of liver regeneration through chemical signals mediated by mechanical stimulation.

A Prospective Randomized Clinical Study to Assess and Compare the Efficacy of Ultrasound Guided Quadratus Lumborum Block versus Transversus Abdominis Plane Block for Postoperative Analgesia in Patients Undergoing Abdominal Hysterectomy Under General Anaesthesia

Abstract Background and Aims: Multimodal analgesia regimens for optimizing the postoperative pain following abdominal surgeries are a crucial component of enhanced recovery after surgery (ERAS), as it reduces postoperative opioid consumption along with their adverse effects. We compared the analgesic efficacy of ultrasound-guided transmuscular quadratus lumborum block (QLB) versus posterior transversus abdominis plane block (TAPB) with respect to duration of analgesia, modified Defense and Veterans Pain Rating Scale (DVPRS) scores for pain, activity, sleep, stress, and mood, respectively, the total amount of rescue analgesic consumption, hemodynamics parameters and side effects, in patients undergoing total abdominal hysterectomy under general anesthesia. Materials and Methods: In this study, which was prospective, randomized, and double-blind, 60 patients of the American Society of Anesthesiologists Physical Status I and II, aged 18–65 years, undergoing abdominal hysterectomy, were randomized into two groups. Group QLB (n = 30) and Group TAPB (n = 30) received bilateral QLB and TAPB with 40 ml of 0.375% ropivacaine, respectively. The data were compared using standard qualitative and quantitative tests. Results: The duration of pain relief was longer in Group QLB compared to Group TAPB (981.83 ± 138.62 min vs. 637 ± 127.02 min, P < 0.0001). The DVPRS score for pain, activity, sleep, stress, and mood, respectively, were significantly lower in Group QLB (P < 0.05). The total rescue analgesic consumption was significantly lesser in Group QLB (103.33 ± 18.26 mg) compared to Group TAPB (150.00 ± 50.85 mg) (P < 0.0001). No significant hemodynamic changes or side effects were observed (P > 0.05). Conclusion: Bilateral QLB significantly prolonged the duration of analgesia with reduced rescue analgesic requirement compared with bilateral TAPB in patients undergoing total abdominal hysterectomy.

Oxygen in the neonatal ICU: a complicated history and where are we now?

Despite major advances in neonatal care, oxygen remains the most commonly used medication in the neonatal intensive care unit (NICU). Supplemental oxygen can be life-saving for term and preterm neonates in the resuscitation period and beyond, however use of oxygen in the neonatal period must be judicious as there can be toxic effects. Newborns experience substantial hemodynamic changes at birth, rapid energy consumption, and decreased antioxidant capacity, which requires a delicate balance of sufficient oxygen while mitigating reactive oxygen species causing oxidative stress. In this review, we will discuss the physiology of neonates in relation to hypoxia and hyperoxic injury, the history of supplemental oxygen in the delivery room and beyond, supporting clinical research guiding trends for oxygen therapy in neonatal care, current practices, and future directions.

Type B aortic dissection in Marfan patients after the David procedure: Insights from patient-specific simulation

ObjectiveAn elevated risk of acute type B aortic dissection exists in patients with Marfan syndrome after the David procedure. This study explores hemodynamic changes in the descending aorta postsurgery. MethodsA single-center retrospective review identified 5 patients with Marfan syndrome who experienced acute type B aortic dissection within 6 years after the David procedure, alongside 5 matched patients with Marfan syndrome without dissection more than 6 years postsurgery. Baseline and postoperative computed tomography and magnetic resonance scans were analyzed for aortic geometry reconstruction. Computational fluid dynamic simulations evaluated preoperative and postoperative hemodynamics. ResultsPatients with acute type B aortic dissection showed lower blood flow velocities, increased vortices, and altered velocity profiles in the proximal descending aorta compared with controls. Preoperatively, median time-averaged wall shear stress in the descending aorta was lower in patients with acute type B aortic dissection (control: 1.76 [1.50-2.83] Pa, dissection: 1.16 [1.06-1.30] Pa, P = .047). Postsurgery, neither group had significant time-averaged wall shear stress changes (dissection: P = .69, control: P = .53). Localized analysis revealed surgery-induced time-averaged wall shear stress increases near the subclavian artery in the dissection group (range, +0.30 to +1.05 Pa, each comparison, P < .05). No such changes were observed in controls. Oscillatory shear index and relative residence time were higher in patients with acute type B aortic dissection before and after surgery versus controls. ConclusionsHemodynamics likely play a role in post–David procedure acute type B aortic dissection. Further investigation into aortic geometry, hemodynamics, and postoperative acute type B aortic dissection is vital for enhancing outcomes and refining surgical strategies in patients with Marfan syndrome.

Effects of a high-sugar mixed-meal on cerebral hemodynamics in young versus middle-aged adults

High-sugar mixed-meal consumption increases both glucose and insulin and elicits mixed vascular effects, with impairments in peripheral microvascular but improved conduit artery function. It is underexplored 1) if a high-sugar mixed-meal elicits vascular segment-specific effects within cerebrovasculature and 2) whether these responses are altered in middle-aged adults with cardiovascular disease (CVD) risk factors. This study sought to test the hypotheses that a high-sugar mixed-meal would elicit differential effects within the middle cerebral artery (MCA) versus downstream hemodynamics, and that changes in cerebral hemodynamics would be blunted among at-risk middle-aged adults compared to young adults. 21 young, healthy adults (24±6 years; 23.7±3.0 kg/m2) and 20 middle-aged adults (55±5 years; 28.2±5.2 kg/m2) with CVD risk factors (hypertension, obesity, or dyslipidemia) consumed a high-sugar mixed-meal consisting of 930 kcals (35.5 g fat, 129 g carbohydrates, 100.5 g sugar, 14 g protein). Vascular measures were taken prior to meal consumption and 30- and 60-min post-meal. MCA pulsatility index (PI), resistance index (RI), mean velocity, and conductance were assessed via transcranial Doppler. Mean arterial pressure (MAP) and common carotid artery diameter were assessed via automated oscillometric cuff and ultrasound, respectively. MCA PI and RI were taken as proxy measures of downstream vascular tone, while MCA mean velocity and conductance, and carotid artery diameter were taken as measures of larger artery cerebrovascular hemodynamics. MCA PI and RI were unchanged in middle-aged adults but increased at 30- (PI+Δ0.13±0.13 au; RI+Δ0.05±0.05 au) and 60-min (PI+Δ0.10 ±0.11 au; RI+Δ0.04±0.05 au) compared to baseline in young adults (p&lt;0.05). MCA conductance increased at 30-min (+Δ0.04±0.08 cm/s per mmHg, p&lt;0.05), carotid diameter increased at 60-min (+Δ0.13±0.20 mm, p&lt;0.05), and MAP tended (p=0.07-0.09) to decrease at 30- (-Δ2.01±5.7 mmHg) and 60-min (-Δ2.26±6.54 mmHg) compared to baseline in both groups. MCA mean velocity was not significantly different across timepoints in both groups. These data suggest a high-sugar mixed-meal may transiently dilate larger cerebral arteries in both young and middle-aged adults but elicit vasoconstriction downstream of the MCA in young adults only. As such, our data suggest that 1) cerebrovascular response to a high-sugar mixed-meal may be vascular segment-specific, and 2) age and risk-factor burden may alter the sensitivity of vasculature downstream of the MCA to a high-sugar mixed-meal. Further research is needed to dissect mechanisms underlying the complex cerebrovascular response to a high-sugar mixed-meal in young versus middle-aged adults with CVD risk factors. 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.

Carbon Dioxide as a Novel Blood Pressure Therapy for Neurogenic Orthostatic Hypotension

BACKGROUND: On standing, people with neurogenic orthostatic hypotension (nOH) experience plummeting blood pressure (&gt;20/10mmHg), crippling symptoms, and syncope. Current blood pressure therapies lack effcacy and have serious side effects. In healthy people, increased inspired CO2 increases blood pressure. This raises the tantalizing possibility that increased inspired CO2 may effectively treat nOH patients. OBJECTIVE: We aimed to understand if increased inspired CO2 can increase standing blood pressure in nOH. METHODS: Seventeen patients with nOH (F=5; 71±8 years) completed three randomized sit-to-stand tests with inspired CO2 maintained 0mmHg (0CO2), +5mmHg (+5CO2) or +10mmHg (+10CO2) relative to baseline. Respiratory and hemodynamics (blood pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance) were continuously measured. Data are reported as mean ± SD. The change (stand-sit) in respiratory and hemodynamics between 0mmHg, +5mmHg and +10mmHg were compared using a repeated measures ANOVA with a Bonferroni correction. RESULTS: Inspired CO2 caused a dose-dependent increase in standing blood pressure (0CO2:-43±25mmHg; +5CO2:-22±26mmHg; +10CO2:-4±30mmHg; p&lt;0.001). Blood pressure changes were predominantly facilitated by increased stroke volume (0CO2:-10±10mL; +5CO2:-5±10mL; +10CO2:0.1±10mL;p&lt;0.001) and cardiac output (0CO2:-0.2±0.6L/min; +5CO2:0.2±0.5L/min; +10CO2:0.7±0.5L/min; p&lt;0.001) as neither the changes in heart rate (p=0.2) nor systemic vascular resistance (p=0.6) were different across CO2 conditions. Breathing CO2 decreased the percentage of time that standing systolic blood pressure dropped ≥20mmHg (0CO2:75±35%; +5CO2:48±38%; +10CO2:32±37%; p&lt;0.001) and fewer patients met the blood pressure criteria for orthostatic hypotension (p=0.02). CONCLUSION: Our data indicates increased inspired CO2 can increase standing blood pressure in nOH patients by increasing stroke volume and cardiac output. CO2 may offer a novel pressor therapy for patients with nOH. This work was supported by a University of Calgary Seed Funding (S.R.R). J.R.B is supported by a Canadian Institutes of Health Research (CIHR) Fellowship, a Libin Cardiovascular Institute Post-Doctoral Fellowship in Women’s Cardiovascular Health, the Natural Sciences and Engineering Research Council of Canada (NSERC) Brain CREATE Program, and a Canadian Cardiovascular Society Fellowship. S.I.R. is supported by the NSERC Brain CREATE Program, an Alberta Graduate Excellence Scholarship, and an Alberta Strategy for Patient Oriented SUPPORT Unit scholarship. A.V.I is supported by a CIHR Fellowship and an Achievers in Medical Science Postdoctoral Fellowship. 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.

Abstract 3138: Atheroprone Flow, Aging, And Oxysterols Impair Endothelial Cell Nuclear Health Via Disruption Of Autoregulatory Perinuclear Cytoskeletal Dynamics

The vascular hemodynamic environment plays a well-known role with progressive pathological conditions such as atherosclerosis, hypercholesterolemia, and aging. Our lab has previously shown that the exposure of oxysterols to endothelial cells (ECs) causes increased cell stiffening. This stiffening effect is compounded when the hemodynamic environment changes from atheroprotective laminar flow to atheroprone oscillatory flow. The increasing EC stiffening demonstrates that these disruptive effects significantly alter cellular biomechanics. The complexity of events associated with these altered biomechanical states leaves many questions unanswered about spatiotemporal changes in the biomechanical structures of endothelial cells exposed to a varying hemodynamic environment and oxysterols. To address this void, we observed the effects of 7-Ketocholesterol exposure (a major oxysterol) on the primary cytoskeletal/biomechanical components (F-actin, Microtubules, Intermediate Filaments, etc.) of human aortic endothelial cells during various time points of laminar/oscillatory flow conditions through a combination of sophisticated multiplexed 6-color labeling, ultra-high resolution 3D microscopy, 3D computer vision, and machine learning. Additionally, we applied these techniques to extracted aortic tissues from young and aged mice (on low fat diet vs high fat diet) and focused on obtaining information from both the laminar flow areas (descending aorta) and the oscillatory flow areas (aortic arch). Our findings demonstrate that oxysterol exposure and aging cause significant remodeling &amp; alteration of crucial endothelial cytoskeletal/biomechanical components and that these alterations are unique to each combinatorial condition. Notably, we find that cytoskeletal remodeling associated with endothelial stiffening is accompanied by major nuclear distortion, a hallmark of aging and senescence which subsequently causes DNA damage and genomic instability. We also find that this nuclear distortion is driven by dynamic biomechanical changes and mediated by the hemodynamic environment, where atheroprotective flow promotes cytoskeletal configurations protecting the nuclei, and atheroprone flow promotes cytoskeletal configurations that leave the nuclei unprotected.

Role of aortic valve replacement in moderate aortic stenosis: a 10-year outcomes study

ObjectivePatients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit...

Hemodynamic Changes in Intrarenal Blood Flow are Associated With Poor Prognosis in Patients With Acute Decompensated Heart Failure.

To evaluate a potential role of different patterns of intrarenal blood flow using Doppler ultrasound as a part of determining the severity of venous congestion, predicting impairment of renal function and an unfavorable prognosis in patients with acute decompensated chronic heart failure (ADCHF). This prospective observational single-site study included 75 patients admitted in the intensive care unit for ADCHF. Upon admission all patients underwent bedside renal venous Doppler ultrasound to determine the blood flow pattern (continuous, biphasic, monophasic). In one hour after the initiation of intravenous diuretic therapy, sodium concentration was measured in a urine sample. The primary endpoint was the development of acute kidney injury (AKI). The secondary endpoints were the development of diuretic resistance (a need to increase the furosemide daily dose by more than 2 times compared with the baseline), decreased natriuretic response (defined as urine sodium concentration less than 50-70 mmol/l), and in-hospital death. According to the data of Doppler ultrasound, normal renal blood flow was observed in 40 (53%) patients, biphasic in 21 (28%) patients, and monophasic in 14 (19%) patients. The monophasic pattern of intrarenal blood flow was associated with the highest incidence of AKI: among 14 patients in this group, AKI developed in 100% of cases (OR 3.8, 95% CI: 2.5-5.8, p&lt;0.01), while among patients with normal and moderate impairment of renal blood flow, there was no significant increase in the risk of developing AKI. The odds of in-hospital death were increased 25.77 times in patients with monophasic renal blood flow (95% CI: 5.35-123.99, p&lt;0.001). Patients with a monophasic intrarenal blood flow pattern were also more likely to develop diuretic resistance compared to patients with other blood flow patterns (p&lt;0.001) and had a decreased sodium concentration to less than 50 mmol/l (p&lt;0.001) in a spot urine test obtained one hour after the initiation of furosemide administration. Patients with monophasic intrarenal blood flow are at a higher risk of developing AKI, diuretic resistance with decreased natriuretic response, and in-hospital death.

Ultrasound-guided laser photocoagulation for the treatment of fetal bronchopulmonary sequestration. Report of two successful cases in Venezuela.

Bronchopulmonary sequestration is a malformation of the respiratory system consisting of non-functioning bronchial and pulmonary tissue, separated from the tracheo-bronchial tree and fed by a blood vessel from the systemic circulation. The incidence is 1 in 5000 births, ranging from 0.15% to 6.45% of pulmonary pathologies. The prognosis is generally favorable, with spontaneous regression of the lesion reported in 50% to 75% of patients. It can cause mass effect, compressing the heart and lung to the point of generating hemodynamic changes and heart failure. There are multiple procedures for treatment and management, mainly in large cases and hydropic fetuses, to improve perinatal prognosis. We present the first two cases of bronchopulmonary sequestration treated in Venezuela by laser photocoagulation of the nutrient vessel and their perinatal evolution, with 100% survival and without any complications recorded in the perinatal period.

Association of Renin-Angiotensin-Aldosterone System Inhibitors With Clinical Outcomes, Hemodynamics, and Myocardial Remodeling Among Patients With Advanced Heart Failure on Left Ventricular Assist Device Support.

We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P=0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P=0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively). RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

Functional Optical Coherence Tomography of Rat Cortical Neurovascular Activation during Monopulse Electrical Stimulation with the Microelectrode Array

This paper presents a study to evoke rat cortical functional activities, including hemodynamic and neural tissue signal changes, by monopulse electrical stimulation with a microelectrode array using functional optical coherence tomography (fOCT). Based on the principal component analysis and fuzzy clustering method (PCA-FCM), the hemodynamic response of different size blood vessels in rat cortex are analyzed, showing that the hemodynamic response of the superficial large blood vessels is more concentrated. In the regions of neural tissue where blood vessels are removed, positive significant pixels (the intensity of the pixel for five consecutive frames is greater than the average value plus triple standard deviation) and negative significant pixels (the intensity of the pixel for five consecutive frames is less than the average value minus triple standard deviation) exist, and the averaged intensity signal responds rapidly with an onset time of ~20.8 ms. Furthermore, the hemodynamic response was delayed by ~3.5 s from the neural tissue response. fOCT can provide a label-free, large-scale and depth-resolved map of cortical neurovascular activation, which is a promising technology to monitor cortical small-scale neurovascular activities.

Evaluating haemodynamic changes: vericiguat in patients with heart failure with reduced ejection fraction.

Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline-directed medical therapies. The haemodynamic effects of vericiguat remain unclear. This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II-IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline-recommended therapies between March and December 2022, with follow-ups completed in June 2023. A balloon-tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30min after (both P<0.05). Reduction in PAWP was also found from 14.5 [9.5, 19.5] mmHg on day 1 to 9.5 [6.5, 12.5] mmHg on day 105 (37, 168) (P<0.05), when vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6), and 10mg 25% (N=3). The consistent reduction in PAWP underscores the well-tolerated nature of vericiguat and its potential to enhance cardiac performance in patients with HFrEF.

Role of Fetal Cardiac ECHO and Fetal Cardiac MRI in Prediction of Post Natal Hemodynamic Maladaptation in Fetuses of Diabetic Mothers

Background: Maternal diabetes mellitus (DM) is defined as a degree of glucose intolerance with recognition during pregnancy (pregestational or gestational, type 1 or type 2), and it is estimated to be 15% in pregnant females in 2019. The current study aimed to study the role of fetal echocardiography and fetal cardiac magnetic resonance imaging (MRI) in anticipation and diagnosis of hemodynamic maladaptation changes in fetuses of diabetic mothers as predictors for (closure of Patent ductus arteriosus (PDA), persistent pulmonary hypertension and diastolic dysfunction) which were confirmed with post-natal echocardiographic and clinical assessment. Methods: This study was an observational follow-up study that included 80 pregnant diabetic females who were following in the specialized clinics of Ain Shams University Hospitals during the period starting from August 2020 till December 2022. Results: Diabetes affected left ventricle (LV) diastolic function and global cardiac function but did not affect LV systolic function (p-value=0.000). Interventricular septum (IVS) thickness had a significant positive correlation with LV- Myocardial performance index (MPI) and indices of DM such as HbA1c. Diastolic dysfunction was the most affected cardiac parameter in infants of diabetic mothers (p-value=0.002). The hemoglobin A1c (HbA1c) was the most significant predictor for IVS thickness in diabetic mothers' fetuses, especially with a long duration of DM (p-value=0.012). Conclusion: Fetal echocardiography in diabetic mothers is essential and the gold standard modality not only for diagnosing structural abnormalities but also for evaluating the cardiac function of the fetuses. Fetal cardiac MRI could be considered a complementary imaging modality that uses no ionizing radiation, good tissue contrast, and a larger field of view.

Effects of Dexmedetomidine on Oxidative Stress, Inflammatory Response, Coagulation Function and Hemodynamics in Patients Undergoing Hysterectomy

&amp;lt;i&amp;gt;Objective&amp;lt;/i&amp;gt; To investigate the effects of dexmedetomidine on oxidative stress, inflammatory response, coagulation function and hemodynamics in patients undergoing hysterectomy. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt; 92 patients who underwent hysterectomy in our hospital from January to September 2023 were selected as subjects. According to the difference in anesthesia, 46 patients were in the control group and 46 in the dexmedetomidine group. Patients in the control group received midazolam anesthesia, and patients in the dexmedetomidine group received dexmedetomidine anesthesia. The changes of oxidative stress, inflammatory response, coagulation function and hemodynamics were compared between T0 (before anesthesia), T1 (10 min after anesthesia), T2 (after extubation) and T3 (24 h after surgery). &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt; At T0, there was no significant difference in T-AOC, GSH-Px, MBP, MCP-1, AT III, FDP, MAP and SpO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; between the two groups (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;gt;0.05). At the time of T1, T2 and T3, the two groups of patients T-AOC, GSH-Px were all lower than T0 (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;lt;0.05), MBP and MCP-1 were all higher than T0 (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;lt;0.05). The levels of T-AOC and GSH-Px in the dexmedetomidine group were significantly higher than those in the control group (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;lt;0.05). The levels of MCP-1 was significantly lower than that of the control group (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;lt;0.05). At the T1 and T2, ATIII levels was lower than T0 (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;lt;0.05), and FDP levels was higher than T0 (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;lt;0.05). At the time of T3, the levels of ATIII and FDP in the dexmedetomidine group recovered to the normal level of T0. There was no significant change in MAP and SpO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; at each time in the dexmedetomidine group (&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;gt;0.05). &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt; Dexmedetomidine can more effectively alleviate the oxidative stress response in patients with hysterectomy, reduce the symptoms of inflammation in patients, improve the coagulation status of patients and have less influence on hemodynamics, and have high clinical value.

In silico analysis of embolism in cerebral arteries using fluid-structure interaction method

Ischemic stroke, particularly embolic stroke, stands as a significant global contributor to mortality and long-term disabilities. This paper presents a comprehensive simulation of emboli motion through the middle cerebral artery (MCA), a prevalent site for embolic stroke. Our patient-specific computational model integrates major branches of the middle cerebral artery reconstructed from magnetic resonance angiography images, pulsatile flow dynamics, and emboli of varying geometries, sizes, and material properties. The fluid-structure interactions method is employed to simulate deformable emboli motion through the middle cerebral artery, allowing observation of hemodynamic changes in artery branches upon embolus entry. We investigated the impact of embolus presence on shear stress magnitude on artery walls, analyzed the effects of embolus material properties and geometries on embolus trajectory and motion dynamics within the middle cerebral artery. Additionally, we evaluated the non-Newtonian behavior of blood, comparing it with Newtonian blood behavior. Our findings highlight that embolus geometry significantly influences trajectory, motion patterns, and hemodynamics within middle cerebral artery branches. Emboli with visco-hyperelastic material properties experienced higher stresses upon collision with artery walls compared to those with hyperelastic properties. Furthermore, considering blood as a non-Newtonian fluid had notable effects on emboli stresses and trajectories within the artery, particularly during collisions. Notably, the maximum von Mises stress experienced in our study was 21.83 kPa, suggesting a very low probability of emboli breaking during movement, impact, and after coming to a stop. However, in certain situations, the magnitude of shear stress on them exceeded 1 kPa, increasing the likelihood of cracking and disintegration. These results serve as an initial step in anticipating critical clinical conditions arising from arterial embolism in the middle cerebral artery. They provide insights into the biomechanical parameters influencing embolism, contributing to improved clinical decision-making for stroke management.

Gamma oscillations induced by 40-Hz visual-auditory stimulation for the treatment of acute-phase limb motor rehabilitation after stroke: study protocol for a prospective randomized controlled trial

BackgroundThe incidence of hemiparetic limb dysfunction reaches 85% in stroke patients, emerging as a critical factor influencing their daily lives. However, the effectiveness of current rehabilitation treatments is considerably limited, particularly in patients with upper extremity impairment. This study aims to conduct a prospective clinical trial to validate the safety and effectiveness of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating post-stroke upper limb dysfunction and to explore the relevant mechanisms.MethodsThis trial is a prospective, randomized controlled, double-blind study. All enrolled patients were randomly assigned to two groups. The experimental group received intervention through 40-Hz visual-auditory stimulation, while the control group underwent intervention with randomly matched visual-auditory stimulation frequencies. The primary efficacy endpoint is the change in motor function. Secondary efficacy endpoints include motor-evoked potentials, cerebral hemodynamic changes, neural network connectivity, and alterations in synaptic-related genes. Safety evaluation included major adverse events, all-cause mortality, and photosensitive epilepsy. Assessments will be conducted at baseline, after a 14-day treatment period, and during subsequent follow-up visits (at 3 and 6 months) post-treatment. The differences between the two groups will be compared.DiscussionThis study will evaluate the safety and efficacy of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating patients with upper extremity dysfunction after an acute cerebral stroke. Concurrently, we will explore potential mechanisms, including changes in synaptic-related genes and neural network connectivity. This trial is expected to provide evidence for the effectiveness of this new technique in treating upper extremity dysfunction after a stroke and improving patients’ quality of life.Trial registrationThe study protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2300076579 on October 12, 2023.

Features of hemodynamics in elderly patients with coronary heart disease using a combination of propofol, ketamine and fentanyl for induction anesthesia

The aim – to analyze hemodynamic changes in elderly patients with coronary heart disease during coronary artery bypass grafting surgery without cardiopulmonary bypass at the stage of induction into anesthesia using propofol, ketamine and fentanyl.Materials and methods. The results of the examination of 20 patients with coronary artery disease over 60 years of age who underwent coronary artery bypass grafting without the use of artificial circulation are presented. The effect of anesthesia on hemodynamics was assessed by mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), and systemic vascular resistance index (SVRI). The following drugs were used for induction: Propofol 1.5 mg/kg, Ketamine 0.5 mg/kg, Fentanyl 2.0 μg/kg, Pipecuronium bromide 0.1 mg/kg. Anesthesia maintenance: Propofol 4 mg/kg/hour, Fentanyl 2.0 μg/kg/hour.Results and discussion. At the time of admission to the surgery room, hemodynamic parameters reflected that the general condition of patients was stable. After the administration of the combination of drugs for induction propofol + fentanyl + ketamine in the dosage according to the study design, it was found that MAP decreased by 18.71 % (p&lt;0,0001), heart rate decreased by 4.72 % (p = 0,2199), CI decreased by 14.37 % (p = 0,0035), and SVRI decreased by 3.93 % (p = 0,41). After insertion of the intubation tube, it was determined that MAP was 92.34±7.26 % of the baseline values (p = 0,0001), heart rate was 100.81±9.77 % of the baseline data (p = 0,848), CI was determined at 110.38±12.37 % of baseline value (p = 0,0769), and SVRI was 83.57±10.7 % of the baseline, respectively. In 25 minutes after successful tracheal intubation, the parameters were re-registered again: MAP = 86.47±6.07 % of the baseline (p &lt; 0,0001); heart rate = 100.08±5.03 % of the baseline value (p = 0,9711); CI = 108.29±9.95 % of baseline data (p = 0,1248); SVRI = 77.86±9.83 % of the baseline (p = 0,0001).Conclusions. Since hypotension is a frequent side effect of traditional drugs for induction of anesthesia, such as propofol and fentanyl, the addition of ketamine to this combination helps to stabilize hemodynamic parameters and prevents undesirable hemodynamic fluctuations.