Artery Blood Flow Research Articles

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.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84vs. 0.68, p-value:.008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

Steady Flow Left Ventricle Unloading Is Superior to Pulsatile Pressure Augmentation Venting During Venoarterial Extracorporeal Membrane Oxygenation Support.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) shunts venous blood to the systemic arterial circulation to provide end-organ perfusion while increasing afterload that may impede left ventricle (LV) ejection and impair cardiac recovery. To maintain flow across the aortic valve and reduce risk of lethal clot formation, secondary mechanical circulatory support (MCS) devices are increasingly used despite limited understanding of their effects on cardiac function. This study sought to quantify the effects of VA-ECMO and combined with either intraaortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) on LV physiologic state and perfusion metrics in a porcine model of acute cardiogenic shock. Shock was induced through serial left anterior descending artery microbead embolization followed by initiation of VA-ECMO support and then placement of either IABP or pVAD. Hemodynamic measurements, LV pressure-volume loops, and carotid artery blood flow were evaluated before and after institution of combined MCS. The IABP decreased LV end-diastolic pressure by a peak of 15% while slightly increasing LV stroke work compared with decreases of more than 60% and 50% with the pVAD, respectively. The pVAD also demonstrated increased coronary perfusion and systemic pressure gradients in comparison to the IABP. Combined support with VA-ECMO and pVAD improves cardiovascular state in comparison to IABP.

Assessment of arterial blood flow in the microvasculature of the lower extremities in patients with chronic ischemia using a single-photon emission computed tomography (SPECT)

Introduction. Obliterating atherosclerosis of the lower extremity vessels is a chronic, steadily progressive disease of the leg arteries, with a high risk of limb amputation and death. Timely diagnosis and adequate treatment will help slow the disease progression, maintain the patient’s good health for a long time and avoid complications. Purpose. To study arterial blood flow in the microvasculature of the lower extremities, to qualitatively and quantitatively assess perfusion disturbances in functionally significant muscles of the lower extremities. Material and methods. Radionuclide examination of the main vessels and microvasculature of the lower extremities was performed in 36 patients, five of them with a diagnosis of lower extremity obliterating atherosclerosis in dynamics. Radiopharmaceuticals was administered through a catheter installed endovascularly above the aortic bifurcation when patients underwent arteriography of the lower extremity vessels, which also involves intra-arterial administration of a radiopaque contrast agent. Results. When processing the radiological study results, we visually assessed the distribution of radiopharmaceuticals in the vascular bed of the lower extremities, identified the asymmetry in the accumulation of radiopharmaceuticals as a percentage, quantified the accumulation of radiopharmaceutical pulses in the projection of the pelvic, thigh, leg and foot muscles, determining the level of accumulation in each of the areas of interest as a percentage. The radiological study results and direct aortic arteriography of the lower extremities with determination of the level of arterial stenosis confirmed the ischemic nature of the pain syndrome; and in the control study, the effectiveness of treatment with an improvement in perfusion parameters. Conclusions. Intra-arterial administration of radiopharmaceuticals makes it possible to assess the condition of the peripheral arterial bed, which has a significant role in the prognosis of lower extremity atherosclerosis and the results of reconstructive interventions. The method makes possible a hybrid topometric comparison of arterio-perfusion maps for diagnosis, planned treatment and monitoring of its results in dynamics.

Effect of FEMOKLIM on the state of blood vessels in hypoestrogenemia and arterial hypertension

The article presents the results of duplex scanning of the common carotid arteries (CCA) and assessment of the structural and functional state of the vascular bed of 57 women with arterial hypertension (AH) with hypoestrogenemia. It was found that with hypertension with a reduced level of estradiol, the lumen of the OCA increases, the speed of blood flow in the carotid arteries decreases, which indicates vascular remodeling. In the studied patients, in every third case, an inertial type of vasomotor reaction is detected before treatment, which indicates the contribution of dishormonosis to the progression of hypertension due to the development of endothelial dysfunction. Combined therapy with phytoestrogens and ACE inhibitors improves the structural and functional characteristics of the vascular wall, reduces arterial stiffness. The drug Femoklim is a source of phytohormones, hormones of entomological origin and natural antioxidants, has a positive effect on the state of the vascular system, improves blood microcirculation, is a capillary protector, has a complex harmonizing effect on the body.

Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).

Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).

Bioresorbable Scaffolds for Below-the-Knee Arterial Disease: A Literature Review of New Developments.

This review aimed to explore the therapeutic effect of bioabsorbable stents in the inferior genicular artery, from the emergence of absorbable bare metal stents to the latest technology in polymer and anti-proliferative eluting drugs mixed with coated bioresorbable vascular stents (BVSs). Currently, there are conflicting data regarding the safety and effectiveness of BVSs in infrapopliteal artery interventions, especially compared to the current generation of drug-eluting stents (DESs). This review will cover the existing data on BVSs in reconstructing the infrapopliteal arterial blood flow and active clinical trials for future iterations of BVSs. In terms of primary patency rate and target lesion revascularization rate, the available research on the effectiveness of BVSs in reconstructing the infrapopliteal arterial blood flow suggests that a BVS is compatible with current DESs within 3-12 months; long-term data have not yet been reported. The ABSORB BVS is the most studied BVS in cardiovascular disease (CAD). Initially, the ABSORB BVS showed promising results. Managing intricate regions in peripheral artery disorders, such as branching or lengthy lesions, continues to be a formidable undertaking. In contrast to the advanced narrowing of arteries seen in standard permanent stent procedures, bioabsorbable stents have the potential to promote the expansion and beneficial merging of blood channels in the latter stages. Furthermore, incorporating stents and re-establishing the endothelial function can diminish the probability of restenosis or thrombosis. Nevertheless, the extent to which bioabsorbable stents may simultaneously preserve arterial patency and guarantee their structural integrity remains uncertain. The powerful and intricate mechanical stresses exerted by the blood in the superficial femoral artery and popliteal artery can cause negative consequences on any implant inserted into the vessel, regardless of its composition, even metal. Furthermore, incorporating stents is advantageous for treating persistent occlusive lesions since it does not impact later treatments, including corrective bypass operations. Evidence is scarce about the use of bioabsorbable stents in treating infrapopliteal lesions. Utilizing bioabsorbable stents in minor infrapopliteal lesions can successfully maintain the patency of the blood vessel lumen, whereas balloon angioplasty cannot offer this benefit. The primary focus of testing these materials is determining whether bioabsorbable scaffolds can provide adequate radial force in highly calcified elongated lesions. Indeed, using "-limus" medication elution technology in conjunction with bioabsorbable stents has previously offered clinical benefits in treating the popliteal artery, as evidenced by limited trials.BVSs for peripheral arterial disease (PAD) show promise and have the potential to offer a less inflammatory and more vessel-friendly option compared to permanent metallic stents. However, current evidence does not yet allow for a universal recommendation for their use. Thus, ongoing, and future studies, such as those examining the newer generation of bioresorbable scaffolds (BRSs) with improved mechanical properties and resorption profiles, will be crucial in defining the role of BRSs in managing PAD.

Computational Analysis of Blood Flow in Healthy Pulmonary Arteries in Comparison to Repaired Tetralogy of Fallot Results: A Small Cohort Study

Characterization of the physiological hemodynamic environment in normal pulmonary arteries is a key factor in understanding pathological conditions. This study aimed to analyze the morphology and hemodynamics in the healthy adult pulmonary bifurcation in comparison to age-matched repaired Tetralogy of Fallot (rTOF) geometries. The pulmonary trunk of five healthy volunteers was reconstructed from 4D Flow-MRI data and was compared to rTOF results. Subject-specific boundary conditions were assigned in both the inlet and outlets of the models, and flow characteristics were analyzed computationally. The morphological and flow features were consistent among the healthy geometries, highlighting the ability of an averaged geometry derived from this small cohort to capture the main flow characteristics. A slightly higher mean time-averaged wall shear stress (TAWSS) was found in the right pulmonary artery, which was also the branch with a higher mean curvature and local Reynolds number. Compared to rTOF results, the averaged healthy geometry demonstrated more than an 8-fold lower value in TAWSS, with the individual patient-specific healthy volunteers showing further reduced TAWSS than the rTOF patients. These observations could be useful in clinical assessment and decision making based on hemodynamic indices.

Short communication: Characterizing arterial and venous blood gases over the gas exchange surface, the chorioallantoic membrane, of embryonic American alligators (Alligator mississippiensis) at two points of development

Assessments of arterial and venous blood gases are required to understand the function of respiratory organs in animals at different stages of development. We measured blood gases in the arteries entering and veins leaving the chorioallantoic membrane (CAM) in embryonic alligators (Alligator mississippiensis). The CAM accounts for virtually all gas exchange in these animals, and we hypothesized that the CAM vasculature would be larger in eggs incubated in hypoxia (10% O2 for 50% or 70% of incubation), which would be reflected in a lower partial pressure of CO2 (PCO2). Contrary to this hypothesis, our measurements revealed no effects of hypoxic incubation on PCO2, and seemingly no increase in vascularization of the CAM in response to incubation in 10% O2. PCO2 was lower on the venous side, but only significantly different from arterial blood at 70% of incubation. The calculated blood flow to the CAM increased with development and was lower in both groups of alligators that had been incubated in hypoxia. Future studies should include measurements of blood parameters taken from embryos held in conditions that mirror incubation O2 levels, in combination with direct measurements of CAM artery blood flow.

548 Metformin normalizes impaired renal and cardiac function in a rat model of transient undernutrition

OBJECTIVES/GOALS: In the U.S., over 4 million people including children experience transient periods of undernutrition annually. Cardio-metabolic and renal diseases are more prevalent in this population. We are investigating therapeutic strategies to reverse the long-term risk of these diseases in a rat model of transient undernutrition followed by refeeding. METHODS/STUDY POPULATION: Thirty six female Fischer rats (3-months of age) were initially divided into 2 groups. Half were fed regular chow (CT) while the other half were severely food restricted (sFR) by 60% from 0-2 weeks (wks) followed by refeeding from 2-14 wks (sFR-Refed). These 2 groups were then subdivided and treated ± metformin (Met) from wk 7 to wk 12 (n=9/group). High precision ultrasound was conducted on live rats to assess heart and kidney function immediately after the sFR period ended (wk 2) and at the end of the study (wk 14). At the conclusion of the experiment, the rats were sacrificed and the histology of the kidney and heart tissues were analyzed in hematoxylin and eosin-stained sections. The protein to DNA ratio was also calculated in homogenates from these tissues. RESULTS/ANTICIPATED RESULTS: In sFR-Refed rats, cardiac output (CO), heart rate (HR) and renal artery blood flow (RBF) were decreased by 11 ± 1.5%#, 7.0 ± 6.0% and 22 ± 0.6%#, respectively, compared to control (CT) rats; #p&lt;0.05. Mean glomerular diameter was reduced in the kidneys of sFR-refed rats compared to CT and this effect was attenuated by metformin treatment [(µm): CT, 406 ± 31; sFR-Refed, 383 ± 11, p&lt;0.06; CT+Met, 393 ± 18; sFR-Refed+Met, 407 ± 18*]. Furthermore, the mean cardiomyocyte thickness was reduced in sFR-Refed rats compared to controls while metformin treatment prevented this effect [(µm): CT, 16.4 ± 3.6; sFR-Refed, 11.5 ± 2.3#; CT+Met, 16.4 ± 3.6; sFR-Refed+Met, 15.9 ± 3.2*]. #p&lt;0.05 vs. CT, same treatment; *p&lt;0.05 vs. Met, same diet; two-way ANOVA. DISCUSSION/SIGNIFICANCE: These findings have promising implications for metformin use to mitigate long-term impairments in heart and kidney structure and function in individuals who have experienced bouts of undernutrition earlier in life for either voluntarily (e.g., very low calorie dieting) or involuntary (e.g., very low food security) reasons.

The effect of underwater massage during hot water immersion on acute cardiovascular and mood responses

PurposeThere is emerging evidence that demonstrates the health benefits of hot water immersion including improvements to cardiovascular health and reductions in stress and anxiety. Many commercially available hot tubs offer underwater massage systems which purport to enhance many benefits of hot water immersion, however, these claims have yet to be studied. MethodsTwenty participants (4 females) completed three, 30-min sessions of hot-water immersion (beginning at 39 °C) in a crossover randomized design: with air massage (Air Jet), water massage (Hydro Jet) or no massage (Control). Cardiovascular responses comprising; heart rate, blood pressure and superficial femoral artery blood flow and shear rate were measured. State trait anxiety, basic affect, and salivary cortisol were recorded before and after each trial. Data were analysed using a mixed effects model. ResultsPost immersion, heart rate increased (Δ31bpm, P < 0.001, d = 1.38), mean arterial blood pressure decreased (Δ16 mmHg, P < 0.001, d = −0.66), with no difference between conditions. Blood flow and mean shear rate increased following immersion (P < 0.001, Δ362 ml/min, d = 1.20 and Δ108 s−1, d = 1.00), but these increases were blunted in the Air Jet condition (P < 0.001,Δ171 ml/min, d = 0.43 and Δ52 s−1, d = 0.52). Anxiety and salivary cortisol were reduced (P = 0.003, d = −0.20, P = 0.014, d = −0.11), but did not vary between conditions. Enjoyment did not vary between conditions. ConclusionThese data demonstrate positive acute responses to hot water immersion on markers of cardiovascular function, anxiety, and stress. There was no additional benefit of water-based massage, while air-based massage blunted some positive vascular responses due to lower heat conservation of the water.

MiR-34a ameliorates arterial blood flow in rats with lower limb arteriosclerosis obliterans via Sirt1 signaling pathway.

In this study, we investigated the impact of microRNA-34a (miR-34a) on lower limb arteriosclerosis obliterans in rats through the Sirtuin 1 (Sirt1) signaling pathway. Thirty-six Sprague-Dawley rats were divided into normal, model, and miR-34a mimics groups. Rats in the normal group were raised normally, while the model group underwent lower limb arteriosclerosis obliterans induction and received saline injections. The miR-34a mimics group also underwent arteriosclerosis obliterans modeling but received miR-34a mimics injections. Immunohistochemistry revealed significantly increased vascular endothelial growth factor (VEGF) expression in both model and miR-34a mimics groups compared to the normal group, with the miR-34a mimics group showing higher levels. Western blotting indicated elevated Sirt1 protein expression in both non-normal groups, with the miR-34a mimics group exhibiting significantly higher levels. Quantitative polymerase chain reaction (qPCR) demonstrated higher levels of miR-34a, VEGF mRNA, and Sirt1 mRNA in the model group compared to the normal group, but significantly lower levels than the miR-34a mimics group. Enzyme-linked immunosorbent assay (ELISA) showed increased VEGF content in the model group compared to the normal group but decreased compared to the miR-34a mimics group. Hemorrheological detection revealed a reduced PU index in both non-normal groups compared to the normal group, with a significant increase in the miR-34a mimics group compared to the model group. Overall, miR-34a upregulation enhanced VEGF expression in rat blood vessels, ameliorating arterial blood flow in lower limb arteriosclerosis obliterans through the Sirt1 signaling pathway.

Computational simulation of blood flow in the right coronary artery and the interaction between the blood flow and the arterial wall

Computational simulation of blood flow in the right coronary artery and the interaction between the blood flow and the arterial wall

Antihistamine Medication Blunts Localized-Vibration-Induced Increases in Popliteal Blood Flow

Localized vibration (LV) of the lower leg increases arterial blood flow (BF). However, it is unclear how LV causes this increase. Understanding the mechanisms of this response could lead to the optimized future use of LV as a therapy. One possible mechanism of LV-mediated BF is through histamine release by mechanosensitive mast cells. The purpose of this study was to measure the BF response of 21 recreationally active young adults (11 male, 10 female, mean age 22.1 years) after 47 Hz and 10 min LV to the calf, with and without antihistamine medication (180 mg Fexofenadine). Each participant received both control (no antihistamine) and antihistamine (treatment) conditions separated by at least 24 h. BF ultrasound measurements (mean and peak blood velocity, volume flow, popliteal diameter, and heart rate) were taken before LV therapy and periodically for 19 min post LV. Using a cell means mixed model, we found that LV significantly increased the control mean blood velocity immediately post LV but did not significantly increase the antihistamine mean blood velocity immediately post LV. Therefore, we hypothesize that a primary mechanism of LV increase in BF is histamine release from mechano-sensing mast cells, and that this response is force-dependent.

Extended period of ventilation before delayed cord clamping augments left-to-right shunting and decreases systemic perfusion at birth in preterm lambs.

Previous studies have suggested that an extended period of ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. However, it is unknown whether this greater rise in PA flow is accompanied by increases in left ventricular (LV) output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale (FO), with decreased systemic arterial perfusion. Using an established preterm lamb birth transition model, this study compared the effect of a short (∼40s, n=11), moderate (∼2min, n=11) or extended (∼5min, n=12) period of initial mechanical lung ventilation before DCC on flow probe-derived perinatal changes in PA flow, LV output, total systemic arterial blood flow, ductal shunting and FO shunting. The LV output was relatively stable during initial ventilation but increased after DCC, with similar responses in all groups. Systemic arterial flow patterns displayed only minor differences during brief and moderate periods of initial ventilation and were similar after DCC. However, an increase in PA flow was augmented with an extended initial ventilation (P < 0.001), owing to an earlier onset of left-to-right ductal and FO shunting (P < 0.001), and was accompanied by a pronounced reduction in total systemic arterial flow (P=0.005) that persisted for 4min after DCC (P ≤ 0.039). These findings suggest that, owing to increased left-to-right shunting and a greater reduction in systemic arterial perfusion, an extended period of ventilation before DCC does not result in greater perinatal circulatory benefits than shorter periods of initial ventilation in the birth transition. KEY POINTS: Previous studies suggest that an extended period of initial ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. It is unknown whether this greater rise in PA flow is accompanied by an increased left ventricular output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale, with decreased systemic arterial perfusion. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent a brief (∼40s), moderate (∼2min) or extended (∼5min) period of ventilation before DCC. Perinatal changes in left ventricular output were similar in all groups, but extended initial ventilation augmented both perinatal increases in PA flow, owing to earlier onset and greater left-to-right ductal and foramen ovale shunting, and perinatal reductions in total systemic arterial perfusion. Extended ventilation before DCC does not confer a greater perinatal circulatory benefit than shorter periods of initial ventilation.