Artery Blood Flow Research Articles

Gestational Long Term High-Altitude Hypoxia and Metabolomic Reprogramming in Uterine Arteries of Adult Sheep

Long term hypoxic stress during pregnancy causes a reduction in uterine blood flow, compromising oxygen and nutrient delivery to the fetus. There are multiple epigenetic factors involved in the structural and functional impairments that underlie the impairments in uterine arterial function. Evidence indicates that oxidative stress plays an important role to the decrements in blood flow following high altitude pregnancy. The purpose of the current study was to test the hypothesis that changes in oxylipin and endocannabinoid signaling are important to the increases in oxidative stress along with changes in glucose and fat metabolism. To further understand the mechanisms associated with disruption of uterine artery blood flow due to high altitude pregnancy, we examined a high altitude pregnant sheep model. Pregnant and non-pregnant sheep were housed either at low (700m) or high altitude (3801 meters) for 110+ days of pregnancy. Uterine arteries were excised from pregnant and non-pregnant sheep and targeted as well as untargeted metabolomic analyses were performed to test the hypothesis that hypoxia increases oxidative stress and reduces oxidative metabolism. Enrichment analysis of the metabolites show that hypoxia impacted several key biochemical pathways. At high altitude there were decreases in Alpha Linolenic Acid and Linoleic Acid Metabolism along with reductions in Pyruvate Metabolism and antioxidants. Further to this, there was an increase in the metabolism of Arachidonic Acid, Glycerolipids, and Methionine, which are linked to inflammation, cell signaling, and cell growth. Fully understanding how increased oxidative stress and inflammatory pathways along with decreased antioxidant capacity and changes in cellular metabolism is tied to malformations in uterine arterial structure and function following high altitude gestation is an active area of investigation. This work was supported by the National Institutes of Health Grants NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, and U24DK097154. Additional support was provided by the Loma Linda University School of Medicine and West Coast Metabolomics Center. 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.

The role of the cardiac vagus in maintaining cardiac function during exercise

There is a strong association between parasympathetic nervous system activity (vagal tone) and physical fitness. High vagal tone is associated with increased capacity to exercise and overall cardiovascular health. Evidence for vagal withdrawal during exercise comes from historic studies examining heart rate control and the use of cholinergic blockers. However, more recent studies have challenged this assumption. We hypothesized that cardiac vagal activity increases during exercise and maintains cardiac function via neurotransmitters other than acetylcholine. The left cardiac vagal branch was identified in anesthetized open-chested sheep. Cardiac innervation of the left cardiac vagal branch was confirmed with lipophilic tracer dyes (DiO). Custom-built coil electrodes were placed around the left cardiac vagal branch. 3-10 days after surgery, conscious, direct recordings of cardiac vagal nerve activity (CVNA), cardiac output, coronary artery blood flow and heart rate were recorded in adult female sheep during whole-body treadmill exercise. Sheep were exercised with pharmacological blockers of acetylcholine (atropine, 250 mg), vasoactive intestinal peptide (VIP) ([4Cl−D-Phe6,Leu17]-VIP 25 μg), or saline control, randomized on different days. In a subset of sheep, the left cardiac vagal branch was denervated. Neural innervation from the cardiac vagal branch is seen at major cardiac ganglionic plexi, and within the fat pads associated with the coronary arteries. Directly recorded CVNA increased during exercise. CVNA increases during the lowest exercise intensity and plateaus as exercise intensity increases. Left cardiac vagal branch, denervation attenuated the maximum changes in coronary artery blood flow (maximum exercise, control: 63.5 ± 5.9 ml/min, n = 8, cardiac vagal denervated: 32.7 ± 5.6 ml/min, n = 6, mean ± SEM. P = 2.5x10−7. Two-way ANOVA-interaction), cardiac output and heart rate during exercise. Atropine did not affect any cardiac parameters during exercise, but VIP antagonism significantly reduced coronary artery blood flow during exercise to a similar level to vagal denervation (maximum exercise, paired: control: 68.2 ± 6.0 ml/min, VIP antagonism: 44.9 ± 3.9 ml/min, n = 6, mean ± SEM. P = 4.8x10−3. Two-way ANOVA-interaction). Our study challenges the conventional view and demonstrates that cardiac vagal nerve activity increases and is crucial for maintaining cardiac function during exercise. Furthermore, our findings show that the dynamic modulation of coronary artery blood flow during exercise is mediated by VIP and that acetylcholine has no role in modulating cardiac function during exercise. This work is supported by the Health Research Council of New Zealand 23/119 (Fellowship. JS) and the New Zealand Heart Foundation (JS, RR). 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.

BLUNTED SKELETAL MUSCLE MICROVASCULAR BLOOD FLOW IS A POTENTIAL UNDERLYING MECHANISM FOR EXERCISE INTOLERANCE IN ADULTS WITH ATRIAL FIBRILLATION

INTRODUCTION & AIMS Approximately 45% of adults living with atrial fibrillation (AF) experience exercise intolerance (EI). However, the mechanisms of EI in AF are not well understood. We aimed to determine whether impaired skeletal muscle microvascular blood flow (MBF), not macrovascular, responses to peak exercise is a plausible explanation for EI in adults with AF. METHODS Adults with AF and healthy controls completed a Modified Bruce treadmill protocol to obtain peak oxygen uptake (V̇O2peak). Skeletal muscle microvascular blood volume, velocity, and flow in the vastus lateralis muscle was assessed using contrast enhanced ultrasound. Superficial femoral artery diameter, blood velocity and flow were assessed using 2D and Doppler ultrasound. Vascular measurements were collected at rest, immediately post-exercise, and 30 minutes post-exercise. RESULTS Nine adults with AF (age: 62±5 years, 66% females, BMI: 29.7±4.2 kg/m2, V̇O2peak: 24.3±6.1 mL/kg/min) and seven controls (age: 63±10 years, 57% females, BMI: 26.7±1.7 kg/m2, V̇O2peak: 31.0±7.5 mL/kg/min) participated. One participant was in AF during testing. A significant group x time interaction in skeletal muscle MBF (p=0.04) and near significant interaction in blood volume (capillary recruitment, p=0.08) was observed. Post-hoc analysis revealed adults with AF had a significantly blunted MBF at 30 minutes post-exercise (-1.3 fold versus control, p=0.01) and reduced microvascular blood volume (i.e. capillary recruitment) pre- and 30 minutes post-exercise (-6.6 fold [p=0.01] and -9.4 fold [p=0.01] versus controls). No differences were observed for changes in skeletal muscle microvascular blood velocity, or femoral artery diameter, blood velocity or flow. CONCLUSION Despite similar femoral artery blood flow responses, adults with AF have lower skeletal muscle MBF responses to peak exercise which may be driven by a reduced capillary recruitment in the skeletal muscle. Our findings provide new insight into vascular complications which may partially explain EI in those with AF.

SEX DIFFERENCES IN CEREBRAL BLOOD FLOW VELOCITY RESPONSES TO EXERCISE IN THE HEAT

INTRODUCTION & AIMS Global warming poses a risk for the development of heat-related physiological impairment, which can be aggravated when exercising in hot conditions. The aim of the present study was to investigate acute effects of exercising in hot conditions on cerebral blood flow velocity and systolic function in healthy individuals and to explore possible sex differences. METHODS The experimental condition consisted of walking on a treadmill, at 5km/h and 2% incline, inside a heat chamber at 40°C (50%RH), for 90 minutes. Middle cerebral artery blood flow velocity (MCAv) and left ventricular global longitudinal strain (GLS; a sensitive index of systolic function), were assessed at baseline and every 30 minutes by means of transcranial Doppler and speckle-tracking echocardiography, respectively. Data is expressed in delta (Δ) and standard error. RESULTS Twenty-six individuals (13♂,13♀ 27.1±1.0yrs, P=0.02) completed the experimental protocol. Both males and females exhibited non-significant increases in MCAv from baseline at 30 minutes (♂Δ=2.55±2.15 P>0.05; ♀Δ=0.54±2.53cm.s-1, P>0.05; interaction P=0.63), followed by significant decreases relative to 30min, at 60min (♂Δ=-4.0±1.23 P=0.04; ♀Δ=-5.41±1.56cm.s-1, P=0.03; interaction P=0.63) and 90 minutes (♂Δ=-6.08±1.37 P<0.01; ♀Δ=-7.39±1.40cm.s-1, P<0.01; interaction P=0.63). In males, there was a significant decrease in GLS from baseline at 30min (Δ=2.44±0.69%, P<0.05), 60 (Δ=2.79±0.73%, P=0.03), and 90 (Δ=3.49±0.89%, P=0.03) minutes; no significant changes were observed in females. CONCLUSION Males and females presented similar patterns of change in cerebral blood flow velocity, including significant decreases with prolonged heat exertion. These changes occur in both sexes, despite changes in systolic strain only being apparent in males. These data suggest that sex differences may exist in the regulation of cerebrovascular responses to exercise in the heat in humans.

Increases in Central Arterial Stiffness and Reductions in Diastolic Velocity in the Large Cerebral Arteries are Associated with Age-Related Decline in Cerebral Blood Flow

Background: Advanced aging is characterized by a reduction in cerebral blood flow (CBF) and an increase in central arterial stiffness. Increased central arterial stiffness results in reduced Windkessel effects and augmented pulsatile arterial blood pressure and CBF. These changes are detrimental to small cerebral blood vessels because of increases in biomechanical stresses associated with the augmented pulsatile arterial blood pressure and CBF. Purpose: To examine the associations of central arterial stiffness with cerebral hemodynamics and age-related reductions in CBF. Methods: 171 healthy subjects (20-81 yrs, 63% F) underwent color-coded duplex ultrasonography of the left and right internal carotid (ICA) and vertebral artery (VA) to characterize individual artery blood flow (BF), velocity, pulsatility, and CBF. Structural Magnetic Resonance Imaging (MRI) was used to measure total brain tissue volume (TBV). Carotid β-stiffness and carotid-femoral pulse wave velocity (cfPWV) were measured via applanation tonometry to assess central artery stiffness. Data: Age was negatively associated with global CBF (r = -0.425, p < 0.001), and positively with cfPWV (r = 0.701, p < 0.001), and carotid β-stiffness (r = 0.660, p < 0.001). Arterial stiffness was negative associated with ICA diastolic velocity (r = -0.280, p < 0.001; r = -0.259, p < 0.001) and VA diastolic velocity (r = -0.280, p < 0.001; r = -0.248, p = 0.001) controlling for sex, body mass index (BMI), education, and TBV. Carotid β-stiffness moderated indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.47 ± 0.13, [-0.74,-0.23]. cfPWV did not moderate the indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.36 ± 0.18, [-0.69, 0.03]. The indirect effect of age on CBF through VA diastolic velocity was not moderated by cfPWV (0.03 ± 0.09, [-0.13, 0.23]) or carotid β-stiffness (-0.17 ± 0.09, [-0.33, 0.01]). Conclusions: Age-related decline in CBF is mediated by the decreases in ICA blood flow diastolic velocity, and this relationship was moderated by carotid β-stiffness. This data suggests that increases in central arterial stiffness and reductions in CBF diastolic velocity in the large cerebral arteries likely plays an important role in age-related decline in CBF. This study was supported by NIH R01HL102457-01 and NIH R01AG033106-01. 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.

Non-vascular ATP-sensitive potassium channel activation does not trigger migraine attacks: A randomized clinical trial.

To investigate the role of NN414, a selective KATP channel opener for the Kir6.2/SUR1 channel subtype found in neurons and β-pancreatic cells, in inducing migraine attacks in individuals with migraine without aura. Thirteen participants were randomly allocated to receive NN414 and placebo on two days separated by at least one week. The primary endpoint was the difference in the incidence of migraine attacks after NN414 compared with placebo. The secondary endpoints were the difference in the area under the curve for headache intensity scores, middle cerebral artery blood flow velocity (VMCA), superficial temporal artery diameter, heart rate and mean arterial pressure. Twelve participants completed the study, with two (16.6%) reporting migraine attacks after NN414 compared to one (8.3%) after placebo (p = 0.53). The area under the curve for headache intensity, VMCA, superficial temporal artery diameter, heart rate and mean arterial pressure did not differ between NN414 and placebo (p > 0.05, all comparisons). The lack of migraine induction upon activation of the Kir6.2/SUR1 channel subtype suggests it may not contribute to migraine pathogenesis. Our findings point to KATP channel blockers that target the Kir6.1/SUR2B subtype, found in cerebral vasculature, as potential candidates for innovative antimigraine treatments.Registration number: NCT04744129.

Limb Position Influences Peripheral Arterial Stiffness Reduction with Reactive Hyperemia

Reactive hyperemia can acutely reduce peripheral arterial stiffness. The reduction in peripheral arterial stiffness with reactive hyperemia has been suggested to be flow dependent. However, no previous studies have manipulated the magnitude of hyperemia. We manipulated blood flow by altering limb position to test the hypothesis that a larger increase in blood flow would lead to a greater reduction in peripheral arterial stiffness. Fourteen healthy young adults (5 women; age: 25 ± 5 years; mean ± SD) were included in this study. Peripheral arterial stiffness assessed via brachial to radial pulse wave velocity (PWV) was measured by placing pulse tonometers simultaneously over the brachial and radial arteries. Doppler ultrasound was used to measure brachial arterial blood flow. Arterial blood pressure was continuously monitored via photoplethysmography on the middle finger of the contralateral hand. Reactive hyperemia was performed with the right arm positioned below (≍50°) and above (≍50°) heart level using a rapid-release cuff positioned on the upper arm, inflated to 220 mmHg, sustained for 5 min, then released. Measurements were recorded before cuff inflation and at 5, 15, and 30 min after cuff release. Repeated measures ANOVA revealed a significant condition effect (p<0.01) with peripheral PWV higher with the arm below the heart. There was a significant time x condition interaction (p<.05). At 5-min after reactive hyperemia, peripheral PWV was reduced more with the arm below the heart (9.58 ±1.65 to 7.26 ± 1.51 m/sec) than above the heart (7.08 ± 1.79 to 5.88 ± 1.43 m/sec). Mean arterial pressure did not change across time points (p>0.05). Peak brachial artery blood flow was greater with the arm below the heart (477.37 ± 145 vs 368.64 ± 137 ml/min; p<.001). The results show that reactive hyperemia produces an acute reduction in brachial to radial PWV. The reduction in peripheral arterial stiffness was greater when the arm was below the heart. The mechanism for position-related differences in the reduction in peripheral arterial stiffness with reactive hyperemia may be associated with the magnitude of increase in blood flow. REJ was supported by National Heart, Lung, and Blood Institute (5T32HL134634-04). 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.

L-Citrulline Supplementation Improves Leg Endothelial Function and Blood Flow Responses to Plantarflexion Exercise in Hypertensive Postmenopausal Women

Menopause and hypertension are associated with macro- and microvascular endothelial dysfunction at rest. Arginine deficiency and low nitric oxide (NO) synthesis may contribute to reduced muscle blood flow (BF) and oxygen delivery to exercising muscles. Improving BF to calf muscles may enhance physical activity. L-Citrulline supplementation (CIT) has improved resting macrovascular endothelial function via increased arginine availability for NO synthesis. Thus, the purpose of this study was to examine the effects of CIT on resting microvascular endothelial function and BF responses to plantarflexion exercise (PFE) in hypertensive postmenopausal women. We hypothesized that CIT would improve microvascular function and BF responses to PFE compared to placebo (PL). Twenty-one hypertensive postmenopausal women were randomized to 4 weeks of CIT (10g/day, n=10) or PL ( n=11). Superficial femoral macro- (flow-mediated dilation; FMD) and microvascular function (5s average peak blood velocity and flow during reperfusion) were assessed by ultrasound at 0 and 4 weeks. Femoral artery BF and vascular conductance (VC) were measured via ultrasound at rest and during 3-minute stages of rhythmic PFE at 5%, 15%, and 30% of 1-repetition maximum (1RM) at 0 and 4 weeks. BF and VC responses to PFE were analyzed as the change from rest to the last minute of each stage. There were no differences between groups in FMD, 5s peak velocity and flow during reperfusion, and vascular responses to PFE at 0 weeks. CIT significantly increased FMD (CIT:Δ1.28 ± 0.42 vs PL:Δ0.01 ± 0.40%, p = 0.04) and 5s peak velocity (CIT:Δ17.44 ± 4.21 vs PL:Δ0.09 ± 4.01 cm/s, p = 0.01) and flow (CIT:Δ220 ± 54 vs PL:Δ35 ± 51 mL/min, p = 0.02) during reperfusion compared to PL. CIT had no effect on BF and VC responses to 5% PFE ( p > 0.05). CIT significantly augmented BF responses to 15% PFE (CIT:Δ82 ± 16 vs PL:Δ22 ± 15 mL/min, p < 0.01) and 30% PFE (CIT:Δ156 ± 33 vs PL:Δ38 ± 32 mL/min, p < 0.01) and VC responses to 15% PFE (CIT:Δ0.80 ± 0.16 vs PL:Δ0.11 ± 0.15 mL*100mmHg/min, p < 0.01) and 30% PFE (CIT:Δ1.49 ± 0.29 vs PL:Δ0.24 ± 0.27 mL*100mmHg/min, p < 0.01) compared to PL. Improvements in FMD were not correlated with BF or VC responses to PFE ( p > 0.05). Improvements in 5s peak velocity were positively correlated with BF responses to 15% PFE ( r = 0.498, p = 0.02) and 30% PFE ( r = 0.532, p = 0.01), and with VC responses to 15% PFE ( r = 0.542, p = 0.01) and 30% PFE ( r = 0.633, p < 0.01). Similarly, augmented 5s flow was positively correlated with BF ( r = 0.461, p = 0.04) and VC ( r = 0.558, p = 0.01) responses to 30% PFE. These findings indicate that CIT improved superficial femoral artery macro- and microvascular endothelial function at rest. However, only improvements in microvascular endothelial function influenced vascular function during leg exercise in hypertensive postmenopausal women. 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.

Myocardial ischemia-reperfusion injury released cellular fibronectin containing domain A (CFN-EDA): A destructive positive loop amplifying arterial thrombosis formation and exacerbating myocardial reperfusion injury

Previous research has identified intravascular platelet thrombi in regions affected by myocardial ischemia-reperfusion (MI/R) injury and neighbouring areas. However, the occurrence of arterial thrombosis in the context of MI/R injury remains unexplored.This study utilizes intravital microscopy to investigate carotid artery thrombosis during MI/R injury in rats, establishing a connection with the presence of prothrombotic cellular fibronectin containing extra domain A (CFN-EDA) protein. Additionally, the study examines samples from patients with coronary artery disease (CAD) both before and after coronary artery bypass grafting (CABG).Levels of CFN-EDA significantly increase following MI with further elevation observed following reperfusion of the ischemic myocardium. Thrombotic events, such as thrombus formation and growth, show a significant increase, while the time to complete cessation of blood flow in the carotid artery significantly decreases following MI/R injury induced by ferric chloride. The acute infusion of purified CFN-EDA protein accelerates in-vivo thrombotic events in healthy rats and significantly enhances in-vitro adenosine diphosphate and collagen-induced platelet aggregation. Treatment with anti-CFN-EDA antibodies protected the rat against MI/R injury and significantly improved cardiac function as evidenced by increased end-systolic pressure-volume relationship slope and preload recruitable stroke work compared to control. Similarly, in a human study, plasma CFN-EDA levels were notably elevated in CAD patients undergoing CABG. Post-surgery, these levels continued to rise over time, alongside cardiac injury biomarkers such as cardiac troponin and B-type natriuretic peptide.The study highlights that increased CFN-EDA due to CAD or MI initiates a destructive positive feedback loop by amplifying arterial thrombus formation, potentially exacerbating MI/R injury.

Acute superior mesenteric artery thrombosis in a 34-year-old male with thrombophilia: a case report

Introduction: Thrombophilic state, marked by extensive formation of blood clots within the vascular system poses a formidable peril, leading to loss of circulatory integrity and systemic well-being. Superior mesenteric artery (SMA) thrombosis is a serious medical disorder characterized by the obstruction of the arterial blood flow to the gastrointestinal tract, which is associated with significant morbidity and mortality. The condition has a plethora of etiological causes. Vague abdominal pain is a common clinical manifestation, and there is a very high mortality rate.Case Presentation: A 34-year-old Pakistani male presented with rapidly worsening acute abdominal pain over a 10-hour period. Clinical examination revealed elevated blood pressure, while other vital signs remained within normal limits. Abdominal examination findings were inconclusive compared to the patient's severe abdominal pain complaint. Contrast-enhanced CT scan indicated a large thrombus in the superior mesenteric artery with radiological features suggestive of intestinal ischemia, extending from the duodeno-jejunal flexure to the mid-transverse colon. Subsequently, the patient underwent exploratory laparotomy with extensive bowel resection and received anticoagulant therapy. He subsequently experienced compensated right lower limb ischemia, treated conservatively with high-dose anticoagulant therapy. Within days, bowel anastomotic leak developed, requiring multiple surgeries. Eventually, the patient progressed to septic shock, followed by multiorgan failure, culminating in a fatal cardiac arrest.Conclusion: Acute mesenteric ischemia, a rare abdominal emergency with an incidence of 6 per 100,000, is associated with a substantial mortality rate, ranging from 58% to 93% among diagnosed cases. The challenges posed by SMA thrombosis include diagnostic complexities, as it frequently manifests with symptoms disproportionate to clinical signs, and results in catastrophic complications, necessitating high suspicion index and prompt intervention.

Pulsatile flow of blood and Cattaneo Christov heat flux model in diseased arteries with variable properties

ABSTRACT The current effort is executed to interpret the heat transmission of combined stenosis and aneurysm in an artery, taking into account variable properties such as viscous dissipation and thermal radiation. We reduced the two directional energy and momentum equations to unidirectional flow by normalizing them under the mild stenotic assumption. After that, a mathematical framework for the physical problem is developed. An intricate nonlinear set of partial differential equations results from this formulation. A suitable numerical method of finite difference is employed on consequent equations to solve them. Afterward, graphical results predict the region of flow and the influence of involved parameters is shown in pictorial form. Furthermore, these solutions are employed to test how certain parameters, like streamlines, flow rate, and wall shear stress, affect blood flow. Using streamlines, we will also observe the general behavior of blood flow patterns.

Curative effect of motherwort combined with ethinylestradiol-cyproterone acetate on dysfunctional uterine bleeding

ABSTRACT Objective This study aimed to investigate the curative effect of motherwort combined with ethinylestradiol-cyproterone acetate (EE/CPA) on dysfunctional uterine bleeding (DUB). Methods Atotal of 68 patients with DUB were divided into a single medication group (treated with EE/CPA) and a combination medication group(treated with motherwort and EE/CPA). The clinical efficacy, uterine hemodynamic parameters, sex hormone levels, coagulation index levels, blood routine test levels, and adverse reactions of patients were evaluated. Results After three months of treatment, total treatment response rate of the combination medication group was significantly higher than that of the single medication group. Decreased uterine volume, endometrial thickness and resistance index (RI), increased pulsatility index(PI), average flow rate, and uterine artery blood flow, as well asreduced follicle-stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (P), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB), thrombin time(TT), platelet count (PLT), red blood cell (RBC), and hemoglobin (Hb)levels were witnessed in patients of the two groups. In thecombination medication group, there exhibited reduced uterine volume, endometrial thickness and RI, elevated PI, average flow rate, and uterine artery blood flow, reduced P, E2, FSH, LH, aPTT, PT, FIB, TT,PLT, RBC, and Hb levels in comparison to the single medication group. Conclusion The combination of motherwort and EE/CPA is clinically effective in the treatment of DUB.

Kidney computed tomography perfusion in patients with ureteral obstruction.

Kidney perfusion on CT is an encouraging surrogate for renal scintigraphy in assessing renal function. However, data on dynamic volumetric CT in patients with kidney obstruction is lacking. Thus, the aim of this study is to determine the feasibility of CT-based renal perfusion using a dynamic volume to assess renal hemodynamics at different degrees and durations of obstruction. We included patients with unilateral kidney obstruction in our single-center, prospective study. The patients were divided into three groups. Patients without dilatation of the pelvicalyceal system (PCS) and normal parenchyma thickness were included into Group 1; patients with PCS dilatation and parenchyma thickness 1.8-2.4 cm-into Group 2; and patients with ureteropyelocalicoectasia and parenchyma thickness less than 1.8 cm-into Group 3. Total of 56 patients were enrolled. In Group 1 mean values of cortical and medullar arterial blood flow, blood volume, and extraction fraction were within the normal range. Changes in contralateral kidney were not determined. Patients from Group 2 showed significant differences in blood flow parameters in the cortical and medulla of the obstructed kidney. No changes in perfusion values in the contralateral kidney was observed. In patients from Group 3 there was a marked decrease in perfusion on the side of obstruction compared to Group 2, indicating that the degree of expansion of the PCS directly correlates with the change in blood flow. However, in the contralateral kidney, these indicators exceeded the normal values of perfusion. CT perfusion allows to objectively assess changes in blood flow in the setting of renal obstruction. The degree of obstruction directly affects the measured rate of blood flow.

Clinical Anatomy of the Superficial Preprostatic Vein and Accessory Pudendal Artery in Robot-Assisted Radical Prostatectomy.

Purpose: We herein describe the superficial preprostatic vein (SPV) anatomy and determine its relationship with the accessory pudendal artery (APA). Materials and Methods: We reviewed 500 patients with localized prostate cancer who underwent conventional robot-assisted radical prostatectomy between April 2019 and March 2023 at our institution. SPV was defined as "any vein coming from the space between the puboprostatic ligaments and running within the retropubic adipose tissue anterior to the prostate toward the vesical venous plexus or pelvic side wall." While APA was defined as "any artery located in the periprostatic region running parallel to the dorsal vascular complex and extending caudal toward the anterior perineum." The intraoperative anatomy of each SPV and APA was described. Results: SPVs had a prevalence rate of 88%. They were preserved in 252 men (58%) and classified as I-, reversed-Y (rY)-, Y-, or H-shaped (64%, 22%, 12%, and 2%, respectively) based on their intraoperative appearance. Overall, 214 APAs were found in 142 of the 252 men with preserved SPV (56%; 165 lateral and 50 apical APAs in 111 and 41 men, respectively). SPVs were pulsatile in 39% men perhaps due to an accompanying tiny artery functioning as a median APA. Pulsations seemed to be initially absent in most SPVs but become apparent late during surgery possibly due to increased arterial and venous blood flow after prostate removal. Pulsations were common in men with ≥1 APA. Conclusions: This study, which described the anatomical variations in arteries and veins around the prostrate and their preservation techniques, revealed that preserving this vasculature may help preserve postprostatectomy erection. ClinicalTrials: The Clinical Research Registration Number is 230523D.

Immediate inflammatory response to mechanical circulatory support in a porcine model of severe cardiogenic shock

BackgroundIn selected cases of cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is combined with trans valvular micro axial flow pumps (ECMELLA). Observational studies indicate that ECMELLA may reduce mortality but exposing the patient to two advanced mechanical support devices may affect the early inflammatory response. We aimed to explore inflammatory biomarkers in a porcine cardiogenic shock model managed with V-A ECMO or ECMELLA.MethodsFourteen landrace pigs had acute myocardial infarction-induced cardiogenic shock with minimal arterial pulsatility by microsphere embolization and were afterwards managed 1:1 with either V-A ECMO or ECMELLA for 4 h. Serial blood samples were drawn hourly and analyzed for serum concentrations of interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, and serum amyloid A (SAA).ResultsAn increase in IL-6, IL-8, and SAA levels was observed during the experiment for both groups. At 2–4 h of support, IL-6 levels were higher in ECMELLA compared to V-A ECMO animals (difference: 1416 pg/ml, 1278 pg/ml, and 1030 pg/ml). SAA levels were higher in ECMELLA animals after 3 and 4 h of support (difference: 401 ng/ml and 524 ng/ml) and a significant treatment-by-time effect of ECMELLA on SAA was identified (p = 0.04). No statistical significant between-group differences were observed in carotid artery blood flow, urine output, and lactate levels.ConclusionsLeft ventricular unloading with Impella during V-A ECMO resulted in a more extensive inflammatory reaction despite similar end-organ perfusion.

In vitro and in vivo evaluation of isoxsuprine loaded invasomes for efficient treatment of diabetes‐accelerated atherosclerosis

Hyperglycemia in diabetes mellitus exacerbates vascular disarray in atherosclerosis by damaging endothelial cells and vascular smooth muscles. It's a major contributor to deaths from cardiovascular disease. Isoxsuprine (IXS) is an oral beta-adrenergic agonist that improves arterial blood flow due to its vasodilatation effect and boosts insulin secretion. However, oral IXS has low efficacy, low bioavailability and patient incompliance due to its high dose frequency, short biological half-life and fast clearance. The goal of this research was to develop a nasal formulation of IXS-loaded invasomes to sustain IXS's release and improve its permeation and efficacy as a potential diabetes-accelerated atherosclerosis treatment. Different IXS-loaded invasomes formulations were developed using design expert software to study the effects of ethanol, phospholipid, and cineole concentrations. Based on the desirability index, the formulation with 1 % ethanol, 0.5 % cineole, and 2.48 % phospholipid was chosen as the optimum formulation. The optimum IXS-loaded invasomes formulation showed an encapsulation efficiency of 72.03 % and a particle size of 210.26 nm. Production of nasal IXS-loaded invasomes formulation increased the permeation of IXS with a ratio of 2.25 and sustained its release. The optimum IXS-loaded invasomes formulation was non-cytotoxic and showed a good binding mode with serum proteins. When optimum IXS-loaded invasomes formulation was evaluated in vivo against a rat model of experimental diabetes and atherosclerosis, it showed anti-diabetic and anti-atherosclerotic effects. It substantially increased the levels of HDL by 45.11 % and substantially decreased the levels of glucose, LDL, triglycerides, and cholesterol by 41.35 %, 89.76 %, 51.01 %, and 60.18 %, respectively. Histopathology also showed that atherosclerotic lesions got improved in rats given optimum IXS-loaded invasomes formulation. In conclusion, nasal administration of IXS-loaded invasomes could be a potential diabetes-accelerated atherosclerosis treatment.

Analysis of the uterine artery pulsatility index on the day of endometrial transformation and pregnancy outcomes of patients undergoing frozen-thawed embryo transfer.

The objective was to analyze the impact of the uterine artery pulsatility index (PI) on pregnancy outcomes by measuring uterine artery blood flow on the day of endometrial transformation in patients undergoing frozen-thawed embryo transfer (FET). This was a case-control study. In total, 2,036 patients who underwent FET at the Third Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were included. The patients were divided into a clinical pregnancy group and a nonclinical pregnancy group according to pregnancy outcome. A multivariate logistic regression model was used to analyze the factors affecting the clinical pregnancy rate. The receiver operating characteristic (ROC) curve was used to determine the optimal mean PI cutoff value of 1.75. After 1:1 propensity score matching (PSM), 562 patients were included. For statistical description and analysis, the patients were divided into two groups: a group with a mean PI > 1.75 and a group with a mean PI ≤ 1.75. The clinical pregnancy group included 1,218 cycles, and the nonclinical pregnancy group included 818 cycles. There were significant differences in female age (P<0.01), infertility type (P=0.04), baseline follicle-stimulating hormone level (P=0.04), anti-Müllerian hormone (AMH) level (P<0.01), antral follicle count (P<0.01), number of transferred embryos (P=0.045) and type of transferred embryo (P<0.01). There was no significant difference in the mean bilateral PI (1.98 ± 0.34 vs. 1.95 ± 0.35, P=0.10). The multivariate analysis results showed that maternal age (AOR=0.95, 95% CI=0.93-0.98, P<0.01), AMH level (AOR=1.00, 95% CI=1.00-1.01, P=0.045), number of transferred embryos (AOR=1.98, 95% CI=1.47-2.70, P<0.01), and type of transferred embryo (AOR=3.10, 95% CI=2.27-4.23, P<0.01) were independent factors influencing the clinical pregnancy rate. The mean PI (AOR=0.85, 95% CI=0.70-1.05; P=0.13) was not an independent factor influencing the clinical pregnancy rate. Participants were divided into two groups according to the mean PI cutoff value of 1.75, and there was no significant difference between the two groups (P > 0.05). In this study, we found that the uterine artery PI on the day of endometrial transformation in patients undergoing FET is not a good predictor of pregnancy outcomes.

Echocardiographic parameters as adjuncts to the Pulmonary Embolism Severity Index in predicting 30-day mortality in acute pulmonary embolism patients.

The Pulmonary Embolism Severity Index (PESI) is a validated tool to predict 30-day all-cause mortality in patients with acute pulmonary embolism (PE) but includes only clinical variables. We aimed to determine the effectiveness of PESI extended with an echocardiographic parameter. This cross-sectional observational study included consecutive patients with acute PE diagnosed with computed tomography pulmonary angiography. Of 117 subjects (57 men, 48.7%), at a median age of 69 (59-80) years, 16 patients died during the 30-day follow-up. Six modified models of PESI with an additional single echocardiographic parameter were created, which increased the predictive value of PESI (area under the curve [AUC] 0.8608): tricuspid annular plane systolic excursion (TAPSE) <18 mm, right ventricular (RV) free wall longitudinal strain (RVFWLS) >-23%, 60/60 sign, RV global longitudinal strain (RVGLS) >-16%, pulmonary ejection acceleration time (AcT) <67 ms, and thrombus in right heart cavities (AUC 0.8657 to 0.8976, respectively, all markers P <0.001). TAPSE, AcT, RVFWLS, and RVGLS showed significant correlations with the PESI score, but not a thrombus in the right heart cavity or the 60/60 sign. As PESI adjuncts, they independently predicted fatal outcomes: thrombus with hazard ratio (HR) 10.04 (95% confidence interval [CI], 2.81-37.12; P <0.001) and the 60/60 sign with HR 4.07 (95% CI, 1.27-12.81; P <0.001). The quantitative echocardiographic parameters of RV systolic function and pulmonary artery blood flow are associated with the PESI score and thus increase its predictive value to a limited extent. PE- specific findings: a thrombus in the right heart cavity and the 60/60 sign are effective adjuncts to the PESI score.

Maternal tadalafil treatment does not increase uterine artery blood flow or oxygen delivery in the pregnant ewe.

Increasing placental perfusion (PP) could improve outcomes of growth-restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)-5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116-117 days' gestational age (dGA; term, 150days), pregnant ewes (n=6) underwent fetal catheterization surgery. At 120-123dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15-75min (TAD 1) and ∼75-135min (TAD 2) post maternal administration (24mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion-Relaxation Combined Imaging for Detailed Placental Evaluation-'DECIDE' technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal-placental blood volume fraction was increased in the TAD 2 period. Fetal and were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal-placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA .

Reduced fetal cerebral blood flow predicts perinatal mortality in a mouse model of prenatal alcohol and cannabinoid exposure

BackgroundChildren exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain, and teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development.Study DesignTo determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow, we performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12–15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55,940 (750 µg/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30 min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day 16 (post-exposure).ResultsAll drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid co-exposure reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in cannabis-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p = 0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p = 0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%).ConclusionsFetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure.