bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P154: Ultrasound Imaging for Serial Measurements of Venous Diameters in Rats
Authors: Krieger-Burke Teresa , Seitz Bridget M , Fink Gregory D , Watts Stephanie W 
Published: July 2021

The purpose of our study was to investigate serial ultrasound imaging in rats as a means to quantify the diameters of splanchnic veins in real time and the effect of drugs on venous capacitance. A 21 MHz probe ( Vevo 2100 imaging system,Visual Sonics Inc.) was used to collect images containing the portal vein (PV) and the superior mesenteric vein (SMV) in anesthetized male Sprague-Dawley rats maintained at 37°C. Stable landmarks were established and we were able to repeatedly locate specific cross-sections of PV and SMV. When controlled for respiratory and cardiac cycles during measurements, respective diameters of these vessels remained within 0.75±0.15% and 0.2±0.10% of baseline (PV: 2.02±0.15 mm; SMV: 1.67±0.05 mm) when located and measured every 5 minutes over 45 minutes (n=3 rats). PV and SMV remained within 1.0±0.6% and 0.38±0.9% from baseline, respectively, when measured on separate days over 10 weeks in a preliminary study using 2 rats. The consistency of raw vessel measurements allowed these vessels to serve as their own control during subchronic pharmacologic interventions.
In a second study, the vasodilator sodium nitroprusside (2 mg/kg, i.v. bolus) was administered to anesthetized rats (n=3) following collection of baseline vessel measurements. PV and SMV diameters increased 37.23±2.4% and 29.77±8.8% from baseline by 30 minutes post drug administration while mean arterial pressure decreased 10.32±1.7 mmHg. Conversely, the administration of the venoconstrictor sarafotoxin (S6C) (5 ng/kg, i.v. bolus) to other anesthetized rats (n=3) decreased PV and SMV diameters 22.10±2.4% and 9.44±1.6% from baseline within 5 minutes, associated with an increase in mean arterial pressure of 12.85±3.2 mmHg.
Together these results support serial ultrasound imaging as a reliable technique to accurately measure acute and subchronic changes in the diameter of splanchnic veins concurrent with blood pressure changes in intact rats. The ability to follow rat abdominal vein diameters in real time will assist in determining the role of the venous circulation in blood pressure regulation.
Abstract 025: Lacking of Gamma Delta T Cells Exaggerate Cardiac Dysfunction in Angiotensin II-induced Hypertension in Balb/cByJ Mice
Authors: Liao Tang-Dong , Xu Jiang , Carretero Oscar A 
Published: July 2021

Gamma Delta T lymphocytes are important innate immune component which express γδ T cell receptor (TCR). These cells are capable of spontaneous secretion of IL-17 and IFN gamma proinflammatory cytokines. Recently, new evidence suggests that the innate and adaptive immune system is involved in the hypertension and end-organ damage. We tested the hypothesis whether deficiency in γδ TCR has a beneficial effect on cardiac function in Angiotension II (Ang II)-induced hypertension. Male Balb/cByj wild-type (WT) and Tcrγδ knockout (Tcrγδ-/-) mice were infused with vehicle or Ang II at dosage of 400ng/kg/min for 4 weeks. Our results showed Systolic blood pressure (SBP) was increased significantly after 1 week of Ang II infusion, and the increase was sustained 4 weeks in WT mice, however in Tcrγδ-/- mice, SBP dropped significantly at 4 weeks compared to WT (table1). Echocardiography data showed that ejection fraction (EF) and shortening fraction (SF) were decreased significantly after Ang II infusion; these effects were exacerbated in Tcrγδ-/- mice given Ang II. Also both mass and chamber dimension increased greater in Tcrγδ-/- mice given Ang II compared to WT (table1). The results indicated Tcrγδ-/- mice given Ang II develop eccentric hypertrophy. We conclude that lacking of γδ T cells has a detrimental effect on cardiac function in Ang II-induced hypertension in Balb/cByJ mice.
table1:
Abstract P365: Blood Pressure Evaluation From Ppg Signal Analysis and Artificial Neural Network
Authors: Lamonaca Francesco , Spagnuolo Vitaliano , De Prisco Serena , Carnì Domenico L , Grimaldi Domenico 
Published: July 2021

The analysis of the PPG signal in the time domain for the evaluation of the blood pressure (BP) is proposed. Some features extracted from the PPG signal are used to train an Artificial Neural Network (ANN) to determine the function that fit the target systolic and diastolic BP. The data related to the PPG signals and BP used in the analysis are provided by the Multi-parameter Intelligent Monitoring in Intensive Care (MIMIC II) database. The pre-analysis of the signal to remove inconsistent data is also proposed. A set of 1750 valid pulse is considered. The 80% of the input samples is used for the training of the network. Instead, the 10% of the input data are used for the validation of the network and 10% for final test of this last. The results show as the error for both the systolic and diastolic BP evaluation is included in the range of ±3 mmHg. Tab.1 shows the results for 20 PPG pulses randomly selected analyzed together with the systolic and diastolic blood pressure furnished by MIMC and evaluated by the trained ANN.
Tab.1 experimental results comparing MIMIC and the ANN results.
Moreover, a suitable hardware to validate the ANN with the sphygmomanometer is designed and realized. This hardware allows clinicians to collect data according to the requirements of the validation procedure. With the sphygmomanometer the systolic and diastolic values are referred to two different PPG pulses. As a consequence, it is proposed a new hardware interface allowing the synchronized acquisition and storage of the PPG signal and clinician voice. For the validation, the clinician: (i) evaluates the BP on both the arms and assesses that no significant differences occur; (ii) plugs the PPG sensor on the finger of one arm; (iii) starts the recording of both the PPG signal and the audio signal; (iv) evaluates the BP on the other arm with sphygmomanometer and says the systolic and diastolic values when detected.
Through suitable post processing algorithm, the Systolic and Diastolic values are associated to the corresponding PPG Pulses. Following this procedure, the dataset to further validate the ANN according the standard is obtained.
Once the ANN is validated it will be implemented on smartphone to have always in the pocket a reliable measurement system for Blood Pressure, oximetry and heart rate.
Abstract P479: Stability of Ambulatory Blood Pressure Patterns Over Time in Children and Adolescents
Authors: Hanevold Coral D , Miyashita Yosuke , Flynn Joseph T 
Published: July 2021

Little is known about the stability of ambulatory blood pressure (ABP) patterns in children and adolescents undergoing evaluation for high blood pressure (HBP). It is possible that children with initially normal ABP may progress to hypertension (HT) or pre-hypertension (PHT), or that those with initial PHT or HT may be normal on repeat. Our objective was to assess stability of ABP patterns over time in children with HBP.

We analyzed changes in ABP classification in patients undergoing a minimum of 2 ABP monitoring (ABPM) studies at least 0.5 years (yrs) apart. Exclusion criteria included known secondary HT, therapy with antihypertensive medication and inadequate recordings. ABPM were interpreted according to the 2014 AHA guidelines using BP thresholds of 95
th
% for sex and height for children ≤17 yrs. For those
>
18 yrs awake and sleep thresholds were 140/85 and 120/70, respectively. Dipping was considered normal if
>
10%, blunted if <10% and reversed if < 0%. For those with > 2 ABPM the difference between the 1
st
and last were analyzed.

Two hundred ABPM on 100 patients (76 males; median age 14.6 yrs at 1st ABPM) were analyzed. Median interval between ABPM was 1.5 yrs. ABP classification was stable in 53% (53/100). As shown in the table 50% (9/18) of those with normal ABPM showed progression to PHT or HT on follow up. PreHT progressed in 31% (8/26) and improved in 38% (10/26). HT improved in 43% (20/46). Dipping designation was stable in 70% (70/100); but blunted dipping normalized in 48% (10/21).
In our population ABP patterns were not stable over time, supporting the need for follow up studies even with normal initial ABPM. If confirmed in larger studies, these findings support greater use of repeat ABPM.
Abstract P110: EBP50 Regulates Vascular Smooth Muscle Cell Growth by Skp2-Mediated Degradation of p21/cip1
Authors: Song Gyun Jee , Barrick Stacey , Leslie Kristen L , Fiaschi-Taesch Nathalie M , Bisello Alessandro 
Published: July 2021

The PDZ domain-containing scaffolding protein, Ezrin-Radixin-Moesin-binding phosphoprotein 50 (EBP50) regulates vascular stenosis following endoluminal vessel injury. Its expression in vascular smooth muscle cells (VSMC) increases after wire injury, and neointima formation is significantly reduced in EBP50 knockout (KO) mice. The molecular mechanisms underlying EBP50 actions in VSMC are unknown.
Genetic ablation of EBP50 reduced VSMC proliferation and was associated with increased (5-fold) expression of the cell cycle inhibitor p21cip1 both in vessels and in primary cells. No differences in mRNA levels of p21cip1 were observed in WT and KO cells. However, the half-life of p21cip1 in KO VSMC was significantly longer than in WT VSMC (80 min vs. 45 min) and p21cip1 levels were similar in WT and KO VSMC treated with the proteasome inhibitor MG132. These observations suggest that EBP50 regulates post-translational degradation of p21cip1. The S-phase kinase-associated protein 2 (skp2) is a component of the E3 ligase complex that degrades p21cip1. The C-terminal four amino acids of skp2 (ProSerCysLeu) are a canonical PDZ-binding sequence. Indeed, co-immunoprecipitation and in-gel overlay assays demonstrated the direct interaction between EBP50 and skp2. Mutation of the C-terminal Leu to Ala (L424A-skp2) abrogated the interaction with EBP50. Skp2 expression was significantly lower in KO than in WT cells and inhibition of EBP50 expression by an shRNA lentivirus decreased skp2 expression in WT cells. Moreover, expression of skp2, but not of the mutant L424A-skp2, in WT cells reduced p21cip1 levels. Therefore, EBP50 regulates both expression and activity of skp2 with attendant effects on p21cip1 and VSMC proliferation.
Collectively, these experiments show that EBP50, by regulating skp2 and p21cip1 expression, controls VSMC proliferation and the progression of neointima formation. These studies identify a novel function for EBP50 in the direct regulation of the cell cycle and provide a mechanistic basis for the remarkable effect of this scaffolding protein on vascular remodeling.
Abstract 223: A Case for Hypoxia and Long QT Syndrome in Sudden Infant Death Syndrome
Authors: Neary Marianne , Mohun Timothy J , Breckenridge Ross A 
Published: July 2021

INTRODUCTION: Long QT syndrome is considered an important factor in the pathogenesis of Sudden Infant Death Syndrome (SIDS). Prolonged QTc intervals (c=corrected for heart rate) in SIDS are sometimes caused by mutations in genes encoding ion channels. Other causes remain largely idiopathic.
HYPOTHESIS: Risk factors for SIDS, including maternal bed sharing, head covering and high altitude, are associated with a reduced oxygen environment. Our studies investigate a link between hypoxia and long QT syndrome in the neonate.
METHODS: We characterised, for the first time, changes in the murine neonatal electrocardiogram (ECG) at: 0, 1, 3, 6, 12, 24 hours (n=12) and 2, 6 and 10 days (n=25) after birth. We investigated whether birth into hypoxia 10% O2 (n=16) and genetically elevating cardiac hypoxic signalling in neonatal mice alters the course of changes in ECG morphology (n=14). We analysed the ECG for heart rate and parameters associated with dysrrhythmia and sudden death, including the QTc interval.
RESULTS: In the hours and days following birth, we observed a steady increase in heart rate (p<0.0001) and decrease in QTc interval (p<0.05). When neonates were raised in hypoxia for 24 hours, the trends in heart rate (p<0.001) and QTc interval (p<0.0001) were abolished and risk of neonatal death was 52% (17 out of 33) over 24 hours. In transgenic neonatal mice with elevated cardiac hypoxic signalling, we observed a significant bradycardia (p<0.0001) and elongated QTc interval (p<0.0001) compared to controls at ten days after birth, with death occurring pre-weaning.
>CONCLUSIONS: Following birth there are significant changes in ECG morphology, including an increase in heart rate and decrease in QTc interval. Hypoxia diminishes these changes resulting in bradycardia and elongated QTc intervals. We hypothesise that the increase in ambient oxygen concentration after birth drives the maturation of cardiac electrical conduction, failure of which predisposes to dysrhythmia and sudden death. This is consistent with known risk factors of SIDS and provides a link between neonatal hypoxia and ECG repolarisation abnormalities.
Abstract 243: The Role of Reactive Oxygen Species in Hyperglycemia-Induced Attenuation of Anesthetic Preconditioning in Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Canfield Scott , Twaroski Danielle , Bai Xiaowen , Kikuchi Chika , Bosnjak Zeljko J 
Published: July 2021

Anesthetic Preconditioning (APC) protects the myocardium from ischemia/reperfusion injury. The cardioprotective effects of APC is diminished or even eliminated in individuals with diabetes mellitus and/or hyperglycemia. The development of patient-specific induced pluripotent stem cells and their differentiation capability has provided us with an
in vitro
model

to study the inefficiency of APC in these individuals.To investigate the underlying mechanisms involved in the attenuation of APC in both diabetic individuals and in hyperglycemia we utilized cardiomyocytes derived from Type 2 diabetic patient and healthy individual iPSCs, (T2DM-iPSCs and N-iPSCs, respectively).

Contracting cardiomyocytes were dissociated and selected by the expression of green fluorescent protein under the transcriptional control of myosin light chain-2v. Cardiomyocytes were exposed to varying glucose concentrations (5, 11, and 25 mM). Lactate dehydrogenase (LDH) release was measured using a colorimetric cytotoxicity assay kit and read spectrophotometrically. Mitochondrial membrane potential and reactive oxygen species (ROS) generation were measured with confocal microscopy.
APC reduced oxidative stress-induced lactate dehydrogenase (LDH) release in cardiomyocytes derived from both N-iPSCs- and T2DM-iPSCs in 5 and 11 mM glucose concentrations, but not in 25 mM glucose. Baseline membrane potential was similar between non-diabetic- and Type 2 diabetic-derived cardiomyocytes; however 25 mM glucose hyperpolarized the mitochondrial membrane potential. T2DM-iPSC-derived cardiomyocytes had an increase in ROS baseline levels compared to N-iPSC-derived cardiomyocytes. Additionally, high glucose concentrations increased oxidative stress-induced ROS production compared to lower glucose conditions in both cell lines.
Our preliminary data shows that high glucose generates excessive ROS and hyperpolarizes the mitochondrial membrane and may contribute to the inefficiency of diabetic and/or hyperglycemic individuals to be anesthetically preconditioned. By utilizing human iPSC-derived cardiomyocytes we can begin to understand the inability of hyperglycemic and diabetic individuals to be anesthetically preconditioned.
Abstract 247: Expression and Activity of K
ATP
Channel in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells of Nondiabetic and Type II Diabetic Patients
Authors: Canfield Scott , Bosnjak Zeljko J , Stadnicka Anna 
Published: July 2021

Pharmacological preconditioning with volatile anesthetics (APC) protects the myocardium against ischemia/reperfusion injury via multiple pathways that include the cardiac sarcolemmal (sarc) KATP channel. However, APC is altered or absent in metabolic diseases such as diabetes. To investigate the underlying mechanisms we evaluated the expression and activity of cardiac sarcKATP channel in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells of non-diabetic (N-iPSCs) and type II diabetic (DM-iPSCs) patients.
Differentiation of human iPSCs into CMs was confirmed by positive immunostaining for cardiac-specific markers and expression of green fluorescent protein under transcriptional control of cardiac promoter myosin light chain-2v that was delivered by lentiviral vector. Immunocytochemical analysis of cardiac sarcKATP channel subunits was carried out with Anti-Kir6.2 and Anti-SUR2A antibodies. Images were captured using a laser-scanning confocal microscope. Single KATP channel activity was monitored from excised inside-out patches at membrane potentials +80 mV to -80 mV, in symmetrical 140 mM K+. The channel was closed by 1 µM glibenclamide and 2 mM ATP.
Immunocytochemical analysis showed the presence and colocalization of Kir6.2 and SUR2A proteins in CMs derived from both N-iPSCs and DM-iPSCs. Interestingly, sarcolemmal expression of these subunits appeared lower in DM-iPSCs. Electrophysiological recordings demonstrated that at 5 µM ATP internal single sarcKATP channels were open more frequently in N-iPSCs (7 of 16 cultures) than in DM-iPSCs (3 of 16 cultures). When measured at +40 mV, the single channel current amplitude (2.2 pA) and conductance (55 pS) were typical for the cardiac sarcKATP channel in N-iPSCs. By contrast, the DM-iPSC channels flickered between the open and closed state, resulting in higher noise level and decreased current amplitude (1.6 pA).
This is the first report of sarcKATP channel expression and activity in CMs differentiated from human N-iPSCs and DM-iPSCs. The study suggests that compromised APC in human diabetic heart may in part result from altered expression of sarcKATP channel subunits and altered channel kinetics.
Abstract 287: Identification of a Novel PKCα Isoform in Heart Transcriptome via RNA Deep Sequencing
Authors: Gao Chen , Lee Jae-Hyung , Xiao Grace (Xinshu) , Wang Yibin 
Published: July 2021

The Protein kinase C (PKC) family of Ca2+ and /or lipid-activated AGC kinases are important regulators of multiple cellular responses including cell growth and programmed cell death. Among these, PKCα is the predominant conventional PKC isoform in heart and has been implicated to have a major impact on cardiac function, hypertrophic response and heart failure. Earlier studies have revealed that the conserved AGC-C-terminal tail containing active site cleft is responsible for regulating AGC kinase activity. The phosphorylation events in AGC-C-terminal tail mediate the activity of kinase by regulating kinase maturation, translocation and substrate interaction. In a genome-wide RNA-Seq analysis in mouse heart, we have identified a novel isoform of PKCα-- due to the insertion of a novel exon in its C-terminal tail. This novel exon has a highly conserved sequence from mouse to human, suggesting a conserved role in PKCα regulation. Tissue analysis showed that this PKCα isoform with Novel Exon (PKCαNE) has enriched expression in heart and skeletal muscle, indicating the involvement of a muscle specific alternative splicing event. The insertion of this novel exon lies between the kinase C-Lobe Tether and Active Site Tether. Biochemistry study in cells showed that both PKCα and PKCαNE were activated and translocated from cytosol to membrane and nucleus in response to PMA. However, upon IGF-1 treatment, PKCαNE showed no activation and could not translocate to either membrane or nucleus in contrast to PKCα. To further explore the mechanism for PKCαNE activation, we have determined the phosphorylation events of this novel isoform. Interestingly, the PKCαNE showed a decreased phosphorylation level at the Turn Motif , which could directly impact its activation and maturation.
In summary, we have identified a novel isoform of PKCα that is enriched in heart and skeletal muscle. The PKCαNE isoform has different activation profile and its biological significance in cell signaling in physiology and diseases remains to be further explored.
Abstract 346: Lipophilic Statins Attenuate Human Atrial Fibroblast Viability In Vitro
Authors: Sran Kiranjit K , Li Yun , Ghavami Saeid , Ngo Melanie , Arora Rakesh C , Kirshenbaum Lorrie , Freed Darren 
Published: July 2021

Cardiovascular diseases (CVD) leading to heart failure are associated with myocardial cell loss and cardiac fibrosis. Hydroxymethylglutaryl-Coenzyme-A Reductase (HMGR) inhibitors ("statins") are widely used to limit cardiovascular events in patients with hypercholesterolemia and CVD by altering their lipid profile. HMGR inhibition reduces cholesterol precursor L-mevalonate production, whose depletion induces autophagy, apoptosis, and endoplasmic reticulum stress in various cell types. However it is unclear if this is a class effect or a phenomenon specific to various compounds. We examined the in vitro effect of HMGR inhibition on human atrial fibroblast (hATF) viability with particular reference to hydrophilic vs lipophilic compounds.
Hypothesis- Lipophilic statins induce cell death in primary hATF via mevalonate depletion; whereas hydrophilic statins do not have any effect on hATF viability.
IRB approval was obtained for collection of hATF from consenting patients undergoing open heart surgery. Cells were treated with atorvastatin, simvastatin or pravastatin (0.1, 1.0 or 10 λM) for 24, 48, 72 or 96 hours. Expression of proteins involved in the regulation of apoptosis and autophagy was assessed using immunoblotting. Cell viability was assessed using MTT assay.
Treatment of hATF with 0.1 - 10 λM atorvastatin or simvastatin (lipophilic statins) resulted in progressively reduced cell viability in time and dose-dependent manner. Viability could be rescued by coincubation with mevalonate. Expression of key apoptotic cascade proteins -Bcl2, Bax and cleaved Caspase3 showed a clear induction of apoptosis. Also, there was an increase in Atg5-12 expression at 24h indicating induction of early autophagic response. Pravastatin (hydrophilic statin) did not affect cell viability or autophagy and apoptosis.
We conclude that statin-induced cell death is mediated by mevalonate depletion, which activates intrinsic apoptotic pathways in hATF. Lipophilic statins impair the viability of hATFs in vitro, whereas hydrophilic statins have no effect on cell growth and cell viability of hATFs. This may represent an additional pleiotropic effect of statins, and may represent a novel therapeutic option for the prevention and treatment of cardiac fibrosis.