bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Effects of an External Pneumatic Compression Device on Local and Systemic Resistance Vessel Reactivity and Limb Blood Flow
Authors: Martin Jeffrey , Borges Alexandra 
Published: June 2021

High pressure external pneumatic compression (e.g. EECP) has been shown to have marked benefits on vascular reactivity and biology. However it is expensive, uncomfortable, and not easily accessible. Alternatively, low pressure EPC is commercially available, does not require medical supervision, and is low risk.PurposeThe purpose of this study was to determine the acute effects of low pressure EPC on resting limb blood flow and resistance vessel reactivity in compressed and non‐compressed limbs of healthy young subjects.MethodsTen (n=10) apparently healthy subjects (aged 27.0 ± 10.2 years) were enrolled in this randomized, crossover design study. Subjects reported in the morning, fasted, for two visits separated by at least 24‐hours. Prior to and immediately following application of EPC or sham for 60 minutes, forearm (FBF) and calf blood flow (CBF) were evaluated at baseline and during 3 minutes of reactive hyperemia (RH) using venous occlusion plethysmography. A peristaltic pulse dynamic compression device was employed for EPC treatment with target inflation pressures of ~70 mmHg applied to the lower limbs.ResultsEPC significantly improved peak CBF, but no differences in resting FBF, peak FBF, resting CBF, total CBF and total FBF were observed.
imageConclusionsEPC significantly improves acute resistance vascular reactivity in compressed limbs, but not non‐compressed limbs, following 60 minutes of treatment. Therefore, application of low pressure EPC may be efficacious in situations where local alterations of resistance vessel reactivity is desirable.Partial support for this study was provided by the Quinnipiac University Interdisciplinary Program for Research & Scholarship and by NormaTec (Newton Centre, MA)
Increased Regional Pannexin1 (Px1) Channel Expression linked to Focal Ischemia is Pro‐Arrhythmic During Stress
Authors: Huke Sabine , Faria Thais , Bennuri Sirish , Chepurko Elena , Gumina Richard , Knollmann Bjorn 
Published: June 2021

Mice with the hypertrophic cardiomyopathy‐linked TnT‐I79N mutation develop arrhythmias during physiological stress. In isolated hearts these arrhythmias are linked to regional ischemia (no decrease in global coronary flow) which causes regional hypoxia and cellular energy deprivation and results in regional conduction velocity slowing and increased arrhythmia susceptibility (84.7% vs 14.3% in control).To test if regional hypoxia/ischemia also occurred spontaneously in vivo in TnT‐I79N mice, we measured mRNA expression of genes up‐regulated by hypoxia (GLUT1, TUBB3, Px1) and found increased expression (0.3fold, 3fold, 10fold respectively). To determine the spatial distribution of Px1‐hypoxia marker we first subjected Px1 ‐βGal reporter mice to coronary ligation and demonstrate that Xgal staining is limited to the perfusion bed of the ligated artery. Then we crossed the TnT‐I79N with the Px1 reporter mice and found that Xgal staining increased in a spatially non‐uniform “patchy” distribution, consistent with focal ischemia. Px1 channels have been implicated in the regulation of vascular perfusion during hypoxia. Strikingly, ablation of Px1 in TnT‐I79N mice reduced the arrhythmia incidence in isolated hearts (to 36.4%) and prevented the focal energy deprivation during stress.Although the physiological role for the increase in Px1 after ischemia remains unclear, Px1 contributes to the increased arrhythmia susceptibility in TnT‐I79N mice. Hence, our data suggest that Px1 may be involved in the regulation of local coronary perfusion and is maladaptive during stress.
Increased Endothelial Expression of Human Soluble Epoxide Hydrolase Negatively Modulates Coronary Reactive Hyperemia in Isolated Mouse Heart
Authors: Hanif Ahmad , Zeldin Darryl , Nayeem Mohammed 
Published: June 2021

Coronary reactive hyperemia (RH) is impaired in hypertrophic hearts. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia / reperfusion injury. Soluble epoxide hydrolase (sEH) is the main enzyme responsible for EETs breakdown. EETs level is decreased in transgenic mice with increased endothelial expression of sEH (Tie 2‐sEH tr). We hypothesized that the isolated mouse heart with increased expression of sEH (Tie2‐sEH Tr) exhibits decreased RH through increased hydrolysis of EETs in response to no‐flow ischemia compared to wild type (WT). Coronary flow (CF) in isolated Tie2‐sEH Tr and WT mouse heart was measured using Langendorff system. Perfused isolated heart was exposed to 15 second ischemia and RH was assessed. Following ischemia, flow repayment volume (RV) (the area under the curve and normalized to heart weight (ml/g)) was significantly decreased in Tie2‐sEH Tr compared to WT(8.7 ± 0.8 in Tie2‐sEH Tr vs. 10.7 ± 0.7 in WT, p<0.05). Moreover, Tie2‐sEH Tr exhibited significantly shorter repayment duration when compared to WT (2.4 ± 0.2 in Tie2‐sEH Tr vs. 3.3 ± 0.4 in WT, p<0.05). At the same time, left ventricular developing pressure (LVDP) and heart rate (HR) were not significantly different between the two groups (LVDP was 168.0 ± 15.1 in Tie2‐sEH Tr vs. 133.1 ± 11.6 in WT, p>0.05; HR was 397.7 ± 24.5 in Tie2‐sEH Tr vs. 387.0 ± 14.1 in WT, p>0.05)Our results demonstrate that increased endothelial expression of sEH (Tie2‐sEH Tr) decreases RH compared to WT. These data suggest that increased level of sEH could have a deleterious effect on myocardial recovery from ischemia. Supported by HL‐114559 to MAN and z01‐ES025034 to DCZ
Effects of Ageing on Nitric Oxide (NO)‐Mediated Cerebrovascular Tone and Autoregulation
Authors: Coney Andrew , Thompson Emma , Marshall Janice 
Published: June 2021

Vascular tone in cerebral circulation is partly determined by NO‐mediated dilatation. NO has also been implicated in the cerebral vasodilatation in response to hypercapnia/hypoxia and at the lower limit of autoregulation. However the role of NO at the upper limit (UL) is unclear. Further, as ageing leads to impaired endothelium‐dependent vasodilatation, we hypothesised these roles of NO may diminish.In anaesthetised male Wistar rats, non‐selective NOS inhibition by L‐NAME (10mg/kg i.v.) increased arterial blood pressure (ABP) by 20±2 and 26±6mmHg in young (Y: 6‐8 weeks, n=16) and old (O: 52‐58 weeks, n=7) rats respectively; concomitantly, gross cerebral blood flow (CBF) recorded from common carotid with external ligated, fell by 0.7±0.1 and 1.2±0.3ml/min.We then infused phenylephrine (0.1–200µg/kg/min i.v.) to raise ABP. The autoregulatory UL for gross CBF was calculated by dual‐line linear‐regression of CBF vs ABP. Similarly, cortical red cell flux (cRCF) was monitored by laser speckle imaging and cRCF UL was calculated. In Y rats after L‐NAME, gross CBF UL was either 187±2mmHg (n=4) or not reached even when ABP was maximally increased to 186±3 (n=12). cRCF UL was also not reached when ABP was increased to 187±2mmHg (n=8). These values are higher than gross CBF UL generated in Y control rats without L‐NAME (168±2mmHg*; P<0.05). In O rats after L‐NAME, neither gross CBF nor cRCF UL was reached in any animal, even though ABP reached 199±5mmHg§ (§: vs Y after L‐NAME). This was also higher than gross CBF UL in O control rats (180±3mmHg*).We suggest NO induces tonic cerebral dilatation in both Y and O animals, such that inhibition allows greater scope for autoregulatory vasoconstriction, raising the UL.British Heart Foundation funding is gratefully acknowledged.
Prolonged Walking Attenuates Hypersympathetic State In Swine With Bilateral Femoral Artery Occlusion
Authors: Yang Hsiaotung , Bowles Douglas , Laughlin M , Terjung Ronald 
Published: June 2021

An increased sympathoexcitation state (SES) has been found in patients with peripheralarterial disease (PAD). Symptoms include an exaggerated response of blood pressure (BP) during increasing physicalactivity. This high SES is detrimental to PAD patients. To determine whether physical training could alleviate SES, 11 Yucatan male pigs received bilateral femoral artery occlusion (BiFemOccl), and were either limited to cage activity (Sed, n=5) or walkedabout 30 min/d (3 mph) on treadmill for 12 wks (Tr, n=6). Arterial baroreflex function was assessed by intravenously infusing adenosine to trig sympathetic drive (1.5 mg /kg) or phenyleprine (PE, 0.1 mg/kg) for parasympathetic drive. BP and heart rate (HR) were recorded through a catheter in the thoracic aorta while animals stood on treadmill. Net change of HR was calculated to change of BP in each animal. Even though resting BP (125 ±5 mm Hg) and HR (110±5 bpm) showed no differences between Sed and Tr group at either prior or post training, the slopes of HR response to reduce BP by adenosine were ‐1.08±0.22 and ‐0.57±0.03 for Sed and Tr group respectively (p<0.05). The HR responses to increased BP by PE were similar between Sed and Tr groups (Slope ‐0.71 ±0.04). The results indicate that swine with BiFemOccl shows exaggerated HR response to baroreceptor unloading and the high SES can be tempered by exercise training. Thus, a chronic exercise program could provide benefit to patients with PDA by reducing the risk of cardiovascular accidents due to the high SES.Supported by NIH grant P01 HL 52490.
Spectral Analysis of Barosensitive Neurons in the Rat Rostral Ventrolateral Medulla
Authors: Huereca D , Barman S , Mueller P 
Published: June 2021

Regulation of blood pressure occurs primarily via the activity of bulbospinal rostral ventrolateral medulla (RVLM) neurons that drive sympathetic nerve activity (SNA). Central and peripheral stimuli influence the activity of RVLM neurons and are reflected in their cardiac and respiratory modulation. Dysregulation of RVLM neurons can lead to increased SNA and the development and maintenance of cardiovascular disease. In this study we used spectral (frequency‐domain) analysis to identify cardiac‐ and/or respiratory‐related (CR, RR) activity in barosensitive RVLM neurons (n=22) and splanchnic SNA of 16 Inactin‐anesthetized rats in which we also recorded arterial pressure (AP) and an index of respiration. SNA had RR activity (0.40±0.05; mean ± SE) and/or CR activity (0.63±0.05) as evidenced by a coherence value > 0.1 at the frequency of respiration and the heart rate, respectively, in the corresponding coherence functions. RVLM unit activity was also shown to be RR (0.40±0.14; n=4) or CR (0.41±0.07; n=4). Moreover, RVLM unit activity cohered to SNA at the frequency of the heart rate (0.39±0.08; n=4) or respiration (0.21; n=1). AP‐triggered analysis (time‐domain analysis) revealed CR activity in 4 other RVLM neurons. These data demonstrate our ability to study the relationships among rat RVLM unit activity, SNA, AP, and respiration, which will allow us to explore whether differences in the strengths of these relationships contribute to changes in SNA and AP under different physiological conditions.HL096787
Lesion of the Area Postrema Reduces Cardiac Sympathoexcitation and Improves Cardiac Function in Heart Failure
Authors: Abukar Yonis , Thomas Colleen , Ramchandra Rohit , Yao Song , May Clive 
Published: June 2021

Background and AimsHeart Failure (HF) is associated with increased cardiac sympathetic nerve activity (CSNA), but the mechanisms causing this are unclear. The area postrema (AP), a brainstem circumventricular organ, plays an important role in controlling SNA. We hypothesized that the elevated CSNA in HF is mediated in part by the AP and that lesioning this region would a) reduce CSNA in sheep with HF and b) improve cardiac function in rats with HF.MethodsIn sheep with pacing‐induced HF, lesion of the AP or sham lesion (n=6/group) was performed when ejection fraction (EF) had fallen to ~50%. In conscious sheep, blood pressure, heart rate and CSNA were recorded when EF was <40%. In rats, AP lesion or sham lesion (n=18/group) was performed before HF was induced by myocardial infarction (MI) and 11 weeks later left ventricular end‐diastolic pressure (LVEDP) was measured in anaesthetised rats.ResultsIn sheep with HF there was a significant decrease in EF (from 74 ± 2 % to 38 ± 1 %, P <0.001) and lesion of the AP significantly reduced the elevated CSNA burst incidence (45 ± 10 vs. 89 ± 3 bursts/100 heartbeats, P<0.01). In rats with HF, LVEDP was significantly lower in the AP lesion group compared with the sham lesion group (11 ± 2 vs 17 ± 2 mmHg, respectively, P<0.05).ConclusionsLesion of the AP significantly reduced the elevated CSNA in sheep with HF and resulted in a lower LVEDP in rats with HF. These findings suggest that the AP plays a critical role in setting the high levels of CSNA in HF and indicate that lesion of the AP reduces the decline in cardiac function post‐myocardial infarction, possibly due to the reduction in CSNA.Support: Melbourne University
Effect of Carotid Body Resection on Baroreflex Control of Blood Pressure During Hypoglycemia
Authors: Limberg Jacqueline , Taylor Jennifer , Dube Simmi , Basu Ananda , Basu Rita , Curry Timothy , Joyner Michael , Wehrwein Erica 
Published: June 2021

BackgroundHypoglycemia results in a reduction in spontaneous cardiac baroreflex sensitivity (scBRS) and a shift in the baroreflex working range to higher heart rates; this effect may be mediated by the carotid chemoreceptors. We hypothesized changes in baroreflex control of heart rate with hypoglycemia would be blunted in carotid body resected patients when compared with healthy controls.MethodsFive patients (3M/2F) with bilateral carotid body resection for glomus tumors and ten healthy controls (7M/3F) completed a 180‐min hyperinsulinemic, hypoglycemic (~3.3 µmol/mL) clamp. Changes in heart rate, blood pressure, and scBRS were assessed.ResultsscBRS was reduced from baseline during hypoglycemia (p<0.01) and was lower in carotid body resected patients when compared with controls (p=0.01). Hypoglycemia‐mediated reductions in systolic and mean blood pressure were significantly greater in patients when compared with controls (p<0.05). Despite lower blood pressures, increases in heart rate with hypoglycemia were blunted in patients (p<0.01).ConclusionReductions in scBRS with hypoglycemia cannot be exclusively attributed to the carotid chemoreceptors; however, the chemoreceptors play a role in resetting the baroreflex working range to higher heart rates during hypoglycemia such that a rise in heart rate is not observed in carotid body resected patients. These data support a contribution of the carotid chemoreceptors to baroreflex control of blood pressure during hypoglycemia and highlight potential widespread effects of carotid body resection in humans.FundingDK090541, HL120570
Quantitative Functional Cardiac Magnetic Resonance Imaging in Mice with Pulmonary Arterial Hypertension
Authors: Breen Ellen , Scadeng Miriam , Murray Fiona , Bigby Timothy 
Published: June 2021

Pulmonary arterial hypertension (PAH) is a condition characterized by elevated mean pulmonary artery pressure, pulmonary vascular remodeling and secondary right heart failure. Mouse models are instrumental in understanding the pathophysiology of PAH and require precise methods to non‐invasively and longitudinally evaluate in vivo cardiac morphology and function. In this study we used magnetic resonance imaging (MRI) to measure in vivo cardiac dimensions in mice with PAH. PAH was induced in C57BL/6 mice using 10% hypoxia and weekly, subcutaneous injections of 20 mg/kg of SU5416 for three weeks. Short axis images at 1 mm intervals from the base to the apex of the heart were collected by proton MRI with a fast low angle SHot (FLASH)‐cine sequence, TE: 2.11 ms and TR: 8 ms. Thirteen images were collected throughout each cardiac cycle. Measurements are presented of right ventricle (RV) lateral wall thickness and ejection fraction. RV wall thickness at the uppermost region of the ventricle was greater in PAH mice than control at end‐diastole (control, 0.30 + 0.05 mm, PAH; 0.48 + 0.06 mm, p< 0.01, n=6) but not different at end‐systole (control, 0.59 + 0.11 mm; PAH, 0.70 + 0.11 mm, n=6). RV ejection fraction was decreased in PAH mice (control, 71.9% + 2.5, PAH 57.6% + 5.4, p=0.04, n=6). These data demonstrate that MR imaging can detect right ventricle remodeling and cardiac dysfunction under in vivo conditions.Funded by Department of Veteran Affairs
Genetic fine‐mapping and gene identification of adiposity traits in outbred rats
Authors: Solberg Woods Leah , He Hong , Holl Katie , Littrell John , Prokop Jeremy , Zagloul Maie , Keele Greg , Baur Brittany , Fox Joseph , Robinson Melanie , Levy Shawn , Valdar William 
Published: June 2021

Obesity and overweight are major risk factors for multiple diseases including cardiovascular disease and type 2 diabetes. Genetic factors are known to contribute significantly to obesity and related traits with heritability ranging from 50‐80%. Human genome‐wide association studies have identified over 50 genes for traits related to adiposity. These genes, however, explain less than 10% of the heritable variance. Heterogeneous stock (HS) rats are outbred from eight inbred strains and allow genetic fine‐mapping to only a few Megabases. The goal of the current study was to use HS rats to fine‐map adiposity traits genome‐wide and identify underlying candidate genes. We measured body weight, body mass index and visceral adiposity in 1090 male HS rats and genotyped all rats using the Affymetrix 10K SNP array. Linkage disequilibrium mapping by mixed model regression was used to identify significant loci. We identified one or more significant loci for all traits, with an average confidence interval of only 2.2 Mb. Using expression data and founder sequence, we identified potential candidate genes within several loci, including those that have previously been identified in human genome‐wide association studies. Protein modeling was used to support a causal role for some of the genes. These results demonstrate the power of HS rats for fine‐mapping metabolic traits and rapidly identifying candidate genes.Supported by NIH R01 DK‐088975 and the Individualized Medicine Institute at MCW.
A Potential Role of Histone Methyltransferase, Dot1l, in Renal Regulation of Acid‐Base Balance
Authors: Nakhoul Nazih , El‐Dahr Samir , Brown Karen , Islam M Toriqul , Khan Altaf , Hering‐Smith Kathleen , Hamm L.Lee , Abdulnour‐Nakhoul Solange 
Published: June 2021

The histone methyltransferase Dot1l is a key epigenetic factor that plays a critical role in embryogenesis, angiogenesis, expression of the collecting duct epithelial Na channel (ENaC)and possibly hypertension. Deletion of Dot1l from renal cells expressing AQP2 resulted in a phenotype whereby kidneys had fewer principal cells and more intercalated cells (IC). It was reported that Dot1l, forming a complex with Af9 (a DNA binding protein) mediated transcriptional repression of ENaC‐α. Because of this transcriptional effect we hypothesized that targeted deletion of Dot1l from the collecting duct may affect expression of other transporters in the collecting duct. To test this hypothesis, we crossed Hoxb7‐Cre to Dot1F/F mice to generate collecting duct Dot1l knockout (Dot1l‐/‐) mice. We then placed control (WT) and renal Dot1l‐/‐ mice on acid diet for 3 days and examined the expression and distribution of Rhbg and Rhcg by immunohistochemistry and Western analysis. Rhbg and Rhcg are NH3/NH4+ transporters located respectively at the basolateral and apical membranes of IC. In response to acid diet Dot1l‐/‐ mice showed an increase in net NH4+ excretion. Rhcg and Rhbg were abundantly expressed but there was no change in Rhcg among the different groups. Rhbg expression was similar in WT & Dot1l‐/‐ under normal diet but was significantly increased in Dot1l‐/‐ mice on acid diet. These data suggest that Dot1l pathways may play a role in affecting renal acid‐base transport. This may be due, at least in part, to the increased expression of Rhbg transporters in DOT1l‐/‐ but a direct effect on transporter function is also possible.Supported by VA Merit Grant
Metformin alters Airway Epithelial Tight Junction Protein Abundance
Authors: Garnett James , Patkee Rgweda , Weekes Alexina , Baker Emma , Baines Deborah 
Published: June 2021

Glucose concentration in the airway surface liquid (ASL) is normally ~0.4mM. Raised blood glucose elevates ASL glucose (up to 4.0mM) which increases the risk of respiratory infection, particularly with methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa. Previously, in an H441/S. aureus co‐culture model we showed that glucose diffused across the epithelium into the ASL via paracellular pathways and was utilised by the bacteria to support their growth. Treatment with metformin reduced paracellular permeability to glucose and supressed glucose‐induced S. aureus growth. In this study, we investigated the effect of metformin on airway epithelial tight junction protein abundance in epithelial/bacterial co‐cultures using western blot and immunocytochemical analysis.S. aureus (8325‐4) addition to the apical surface of H441 monolayers for 7 hours decreased E‐cadherin (p<0.001,n=13) and occludin abundance (p<0.05,n=5), but had no effect on claudin‐1 (p>0.05,n=3). Pre‐treatment of H441 monolayers with metformin (1 mM; 18 hours) prior to S. aureus addition, had no effect on E‐cadherin, but enhanced occludin abundance (p<0.05,n=5). P. aeruginosa (PA01) addition to the surface of Calu‐3 airway epithelial monolayers reduced transepithelial resistance (TEER) (from 669±27 to 489±20Ω.cm2; p<0.05, n=5). Metformin attenuated this effect (551±16Ω.cm) and inhibited glucose‐induced bacterial growth (both p<0.05, n=4). P. aeruginosa had no effect on E‐cadherin or claudin‐1 abundance in Calu‐3 monolayers, but abolished occludin expression (p<0.0001, n=3). Metformin did not reverse the effect on occludin but increased claudin abundance in the presence and absence of P. aeruginosa (p<0.01, n=3)
Exercise Performed at Different Times of the Day Has Different Effects on Ambulatory Blood Pressure, Heart Rate and Arterial Stiffness
Authors: Brito Leandro , Rezende Rafael , Cipolla‐Neto José , Forjaz Claudia 
Published: June 2021

ObjectiveTo analyze ambulatory blood pressure (BP), heart rate and arterial stiffness responses after performing aerobic exercise in the morning and evening.Methods13 young pre‐hypertensive men underwent four experiments conducted in a random order: two at 9 am and two at 6:30 pm. At each time of day, a control and an exercise session (cycle ergometer 45 min, 50% VO2peak) were performed. After the sessions, ambulatory monitoring was performed for 24 hours taken measures each 15 minutes. Ambulatory systolic, diastolic and mean BP, as well as heart rate and arterial stiffness index were calculated for 24h, daytime and nighttime periods. At each time of day, data were compared between control and exercise sessions by a paired T‐test, p蠄0.05.ResultsAfter evening exercise, nighttime systolic BP was lower than the control session (116±11 vs. 120±10 mmHg, p=0.04). None of the other variables showed difference after evening exercise. After morning exercise, heart rate was greater than control for all periods (24h 80±7 vs. 76±6 bpm, p=0.02; daytime 83±8 vs. 79±7 bpm, p=0.01; and nighttime 72±8 vs. 67±5 bpm, p=0.05), and arterial stiffness was greater for 24h and daytime (0.298±0.098 vs. 0.233±0.068 U, p=0.01, and 0.432±0.137 vs. 0.322±0.089 U, p=0.02, respectively). None of the other variables showed differences after morning exercise.ConclusionAerobic exercise performed in the evening decreased nighttime BP while exercise performed in the morning increased heart rate and arterial stiffness. Financial support: CNPq: 472288/2011‐3, FAPESP: 2011/03584‐8.