bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that flow mediated dilation dynamics differ in smokers versus non‐smokers: a pilot study (677.6)
Authors: King Trevor , Findlay Briar , Gupta Parnika , Szijgyarto Ingrid , Pyke Kyra 
Published: June 2021

Endothelial function is impaired in smokers as measured via handgrip exercise (HGEX) induced flow mediated dilation (FMD). The goal of this pilot study was to determine whether the dilation and reconstriction dynamics of FMD were impaired in young male smokers. 8 smokers and 14 non smokers (age 21 ± 2) performed 10 minutes of rhythmic HGEX bracketed by 4 minutes of arterial compression to ensure rapid shear stress onset and return to baseline. Brachial artery diameter and blood velocity assessed via echo and Doppler ultrasound. Shear stress estimated as shear rate (SR = brachial artery blood velocity/diameter). Dynamic parameters: time to onset of dilation and reconstriction (TD1); rate of dilation and reconstriction(Tau1). Alpha set at P<0.1, data ± SD. SR stimulus did not differ between groups(p=0.60). TD1 of dilation was longer in smokers (29.7 ± 17.0 s) vs. non smokers (17.5 ± 11.9 s)(p=0.06), and Tau1 was faster among smokers (27.5 ± 9.5 s vs. 48.6 ± 32.4 s, p = 0.09). Constriction dynamics were not different between groups (p>0.1). Among smokers, dilation tau1 was faster than reconstriction tau1(27.5 ± 9.5 s vs. 72.3 ± 56.4 s, p=0.06), whereas there were no differences between onset and constriction dynamics among non‐smokers (p=0.43). These results suggest that smoking impacts the dynamics of the vascular response to shear stress with a preferential impact on dilation vs. reconstriction.Grant Funding Source: Supported by NSERC and CFI
Quantification of microvascular hemodynamic using cross correlation analysis of intravital microscopy videos (678.11)
Authors: Ortiz Daniel , Briceno Juan , Cabrales Pedro 
Published: June 2021

Blood flow patterns and endothelium interactions are of great importance for the progression of cardiovascular diseases, thus quantitative analysis of blood flow dynamics at the microcirculation level of great relevance. Regulatory mechanisms mediated by blow flow have been studied in detail using in vitro approaches. However, these mechanisms have not been completely validated in vivo due to technical limitations involved in the quantification of flow patterns in the mcirocirculation with the required level of detail. Intravital microscopy combined with high‐speed video recordings has been used for the analysis of blood flow in small blood vessels of chronic and acute experimental animal tissue preparations. This tool is used to study the interaction between the flowing blood and the vessel walls of arterioles and venules with great temporal and spatial resolution. Our objective is to develop a simple and robust cross‐correlation algorithm for the automatic analysis of high‐speed video recordings of microcirculatory blood flow. The algorithm has been validated using in vitro (glass microchannels) and in vivo (window chamber models) systems. Results indicate that the algorithm’s ability to estimate the velocity of local red blood cells (RBCs) as a function of blood vessel radius and time is highly accurate.The algorithm could be used to explore dynamic changes in blood flow under different experimental conditions including a wide range of flow rates and hematocrit levels. The algorithm can also be used to measure volumetric flow rates, radial velocity profiles, wall shear rate (WSR), and wall shear stress (WSS). Several applications are presently explored, including the analysis of velocity profiles in the branches of arterial bifurcations. Our work demonstrates the robustness of the image cross‐correlation technique in various flow conditions and elucidates its potential application for in vivo determination of blood flow dynamics in the microcirculation.Grant Funding Source: Supported by: NIH R01 HL52684, R01 HL064395 and R01 HL062318 and ARMY: W81XWH‐11‐2‐0012
Age‐related progression of bone marrow blood vessel ossification in rat and, potentially human, long bone (678.19)
Authors: Prisby Rhonda 
Published: June 2021

BACKGROUD: Bone perfusion and bone vessel location, density and function are associated with bone mass. We recently demonstrated ossification of bone vessels in rats. The objective of this study was to assess ossification with advancing age and to confirm ossification in human patients. METHODS: Femora from young (n=8) and old (n=8) male Fischer‐344 rats were examined to quantify patent vs. ossified and calcified vessels. Femora from additional young (n=5) and old (n=5) rats were analyzed for vessel ossification via µCT. Femoral vessels from a patient with ASVD and from rats were examined via microscopy. RESULTS: Isolated vessels (human and rat) had osteocyte lacunae on the surface. Patent vessel number was reduced (p<0.05) with age (0.47±0.05/mm2 vs. 0.29±0.05/mm2). Higher (p<0.05) volumes of ossified vessels were evident with age (0.01±0.01% vs. 0.49±0.11%). Calcified vessel volume/tissue volume (0.32 ±0.08% vs. 1.16±0.31%) and /patent vessel volume (17.2±5.9% vs. 62.4±15.5%) were augmented (p<0.05) in old rats. Ossified vessel number was higher (p<0.05) in old rats (0.07±0.01/mm2 vs. 0.19±0.04/mm2). CONCLUSIONS: For the first time, ossification of human bone marrow blood vessels was demonstrated. Ossification begins in youth and progresses with age, corresponding with a reduced number of patent vessels. Such pathology is presumably associated with bone disease.Grant Funding Source: Supported by NIH (NIAMS) Grant 1R15AR062882‐01
CD34+ stem cell treatment for acute ischemic stroke (678.20)
Authors: Gavins Felicity , Smith Helen , Granger D. Neil 
Published: June 2021

Stroke is the most common cause of significant acquired disability in adults for which only limited therapeutic strategies exist, limited by a brief therapeutic window (<4 h). No pharmacological compound to date has been found to increase recovery reliably once brain injury has occurred. Stem cell transplantation techniques offer novel approaches that may enhance endogenous repair mechanisms, promote brain recovery and regeneration, and may ultimately reduce neurological deficits in stroke patients. While showing positive results, current stem cell therapies are highly inefficient, with a tiny percentage of injected cells arriving at the intended injured site.Following on from our previous open label phase 1 study in stroke patients, to determine the safety and feasibility of treatment with immunoselected CD34+, we have used a murine model of ischemic stroke (the middle cerebral artery occlusion model) to investigate the migration of CD34+ stem cells to the infarcted area. Using both intravital and confocal intravital microscopy we have been able to explore both leukocyte and stem cell trafficking in the murine brain pre and post stroke. Both leukocyte rolling and adherence were increased in mice subjected to stroke vs. sham mice. Stem cell treatment reduced these leukocyte interactions, with effects observed upto two weeks post stroke. These novel data suggest a therapeutic potential role for the use of CD34+ stem cells for acute ischemic stroke
Gender‐based protection against microvascular dysfunction with depressive symptoms in mice (678.3)
Authors: Skaff Paulina , Stanley Shyla , Brooks Steven , Butcher Joshua , Frisbee Jefferson 
Published: June 2021

Human subjects suffering from clinical depression frequently experience these symptoms as a result of the presence of chronic, unresolved stresses in their environment. This can have significant impacts on a poor outcome for cardiovascular health, and one of the central markers of dysfunction is a blunted vasodilator response to imposed stimuli. There is increasing evidence that this may be due to a reduction in the bioavailability of signaling molecules contributing to the dilator response. To investigate this in an animal model of chronic stress and depressive symptoms, we used the unpredictable chronic mild stress (UCMS) model to simulate human clinical depression in mice. In response to the UCMS protocol, all mice exhibited significant depressive symptoms, although this was increased in female mice vs. males. Endothelium‐dependent dilator responses in ex vivo aortic rings in response to increasing concentrations of methacholine were reduced by UCMS, and this effect was more extensive in male than in female mice. Treatment of rings with the antioxidant TEMPOL improved dilator responses in vessels from both genders. Inhibition of NOS (L‐NAME) had no impact on dilator responses in rings from UCMS males, but reduced responses in females. Inhibition of cyclooxygenase (indomethacin) blunted dilation in UCMS males but had a smaller effect on responses in UCMS females. These results suggest that, while female mice are more susceptible to depressive symptoms, they are somewhat protected from the impaired vascular function. While male mice are less susceptible to the depressive symptoms their vascular function is impaired to a greater extent.Grant Funding Source: Supported by National Institutes of Health and American Heart Association
Contribution of Kv1 channel activity to myogenic responses in skeletal muscle arterioles with aging and exercise training (678.7)
Authors: Ghosh Payal , Solis Fredy , Dominguez Jimmy , Delp Michael , Muller‐Delp Judy 
Published: June 2021

The impaired myogenic constriction of skeletal muscle arterioles observed with advancing age may be the result of increased Kv channel activity. Exercise training has been shown to restore myogenic responses. The purpose of this study was to determine the role of Kv1 channel activity in these adaptations in reactivity.Young and old male Fischer 344 rats were randomly assigned to either a sedentary (YSED and OSED) or exercise trained (YET and OET) group. Training consisted of treadmill running (15m/min, 15°incline, 1hr/d, 5d/wk for 10 wks). Soleus muscle first order arterioles were isolated and cannulated for in vitro study. Myogenic responsiveness was determined by exposing arterioles to incremental changes in intraluminal pressure from 0 to 140 cmH20, either in the presence or absence of Kv1 channel blocker correolide.Exercise enhanced myogenic tone in arterioles from both old and young rats and restored myogenic responsiveness in old rats to that of YSED rats. Kv1 channel blockade abolished the training effect in young rats, and resulted in greater constriction at lower pressures in YSED, but had no effect in YET rats. In both OSED and OET rats, Kv1 channel blockade led to increased myogenic constriction; however, the training effects persisted.These results suggest that Kv1 channel activity may play a role in modulating myogenic tone in young and old rats. Increased myogenic constriction after training in young rats may be mediated through a reduction in Kv1 channel activity. However, improved myogenic responsiveness with training in old rats appears to be mediated through a different pathway.Grant Funding Source: Supported by NIH R01HL090937
Bcl‐2 expression in endothelial cells impacts postnatal retinal vascular development without affecting retinal neovascularization (679.2)
Authors: Sorenson Christine , Zaitoun Ismail , Wang Shoujian , Sheibani Nader 
Published: June 2021

Bcl‐2 plays an important role in retinal vascular homeostasis. Global lack of Bcl‐2 expression results in attenuation of postnatal retinal vascular development and neovascularization during Oxygen‐induced Ischemic Retinopathy (OIR).To determine the impact lack of Bcl‐2 expression in endothelial cells has during retinal vascular development, remodeling, and neovascularization, we generated mice carrying a conditional Bcl‐2 allele (Bcl‐2Flox/Flox) and VE‐cadherin‐cre called Bcl‐2EC mice. Bcl‐2EC mice displayed decreased numbers of endothelial cells at both 3 and 6 weeks of age compared to wild‐type controls. However, the remodeling of the retinal vasculature proceeded with similar percentage loss of endothelial cells in both wild‐type and Bcl‐2EC mice. In addition, Bcl‐2EC mice had increased pericyte numbers at 6 weeks of age contributing to a lower EC/PC ratio. Retinal arteriogenesis was also decreased in Bcl‐2EC mice similar to what we observed in global Bcl‐2 knockouts. However, unlike the global knockouts the migrating front of the retinal vasculature proceeded normally and neovascularization during OIR occurred at levels similar to wild‐type mice. Therefore, our data suggests that Bcl‐2 expression modulates endothelial cell survival impacting postnatal retinal vascular development with minimal impact on retinal neovascularization during OIR.Grant Funding Source: Supported by R21EY023024
Modest weight gain and weight loss alter expression of sex hormone binding globin in healthy men: implications for endothelial function (680.15)
Authors: Singh Prachi , Covassin Naima , Singh Ravinder , Cundrle Ivan , Sert‐Kuniyoshi Fatima , Romero‐Corral Abel , Davison Diane , Lopez‐Jimenez Francisco , Jensen Michal , Somers Virend 
Published: June 2021

Background: Decreased testosterone (TTST) and sex hormone binding globin (SHBG) contribute to development of cardiometabolic disorders in obese men. We aimed to determine the effect of weight gain and weight loss on TTST and SHBG in healthy men and to examine their relationship with endothelial function.Method: 25 normal weight healthy men underwent an overfeeding protocol to gain 5% body weight over 8 weeks. Following weight gain, they underwent 8 weeks of weight loss. TTST, SHBG and endothelial function (brachial artery flow‐mediated dilation, FMD) were measured at baseline (T1), after weight gain (T2) and after weight loss (T3).Results: Volunteers gained 4 ± 1.3 kg and subsequently lost 3.2 ± 1.5 kg of body weight. TTST levels did not change (T1: 18.85 ± 6.2 nmol/L, T2: 19.3 ± 6.9 nmol/L, T3: 20.3 ± 7.6 nmol/L). However, SHBG decreased during weight gain (p=0.04) and increased during weight loss (p=0.0005) (T1: 22.8 ± 10.5 nmol/L, T2: 20.8 ± 11.1 nmol/L, T3: 25.58 ± 11.5 nmol/L). Furthermore, SHBG reduction during weight gain tended to correlate with decreases in FMD (p=0.06; R2=0.15). During weight loss, increases in SHBG correlate negatively with changes in FMD (p=0.008; R2=0.32).Conclusion: In normal weight healthy men, SHBG decreases with modest weight gain and increases with weight loss. TTST does not change. Changes in SHBG partly predict improvements in endothelial function with weight loss.Grant Funding Source: Supported by AHA 11SDG7260046, R21 DK81014, AHA 13POST16420009
Influence of sexual dimorphism on endothelial morphology, metabolism and mechanics (680.18)
Authors: Huxley Virginia , Stockard Kevin , Bingaman Susan 
Published: June 2021

Microvessels are dynamic complexes of vascular structures, formed elements of blood carried by plasma, parenchymal cells, and the interstitial matrix through which they course. Only recently how these elements interrelate to maintain homeostasis differently, often subtly, in females (F) and males (M) is being studied and the implications recognized. We tested the hypothesis that the phenotype of the endothelial cells (EC) lining the vasculature, known to differ by organ and vessel type, would not differ with sex. EC isolated from the aorta and microvasculature of skeletal muscle (SKM) and mesentery (MES) of F and M adult rats were studied with respect to morphology, growth, metabolism and mechanics. We rejected our hypothesis as profound sex‐differences existed for each EC source. For example, F aortic EC were smaller (13 vs 16 μm) and their numbers in culture were greater than M; in SKM and MES F>M (16 vs 15 and 18 vs 15 μm, respectively). Sex and tissue differences were noted for VE Cadherin, eNOS, Insulin receptor β, androgen receptor, and estrogen receptor α and β expression. With respect to fiber orientation and frequency as assessed by atomic force microscopy, overall actin fiber orientation converged in one direction more uniformly in F than M and differed by tissue source. While aortic EC lactate production was sex‐independent, F<M for microvessel EC. Understanding sexual dimorphism in EC will assist in delineating the sources of sex‐differences that influence both the incidence and severity of diseaseGrant Funding Source: Supported by NIH DK 095501 and MU Div of Pulm & Critical Care Medicine
Cardiac proteome analysis of sex and estrogen receptor β effects in pressure overload (680.4)
Authors: Kararigas Georgios , Fliegner Daniela , Forler Stefanie , Klein Oliver , Schubert Carola , Klose Joachim , Regitz‐Zagrosek Vera 
Published: June 2021

The cardiac response to pressure overload (PO) differs between the sexes and estrogen receptor (ER) β is considered cardioprotective. However, the underlying mechanisms are poorly understood. We aimed at the analysis of the effects of sex and ERβ in PO taking a proteomic approach. Two‐month‐old C57BL6 male (M) and female (F) wild‐type (WT) and ERβ knockout (BERKO) mice were subjected to transverse aortic constriction (TAC) or sham surgery (n = 4/group). The proteome of left ventricular samples was separated by high‐resolution 2‐dimensional polyacrylamide gel electrophoresis. At nine weeks post operation, TAC led to a greater increase in heart‐weight‐to‐tibia‐length ratio in WT M (128%; P < 0.05) than in WT F (54%; P < 0.05) mice, while this difference in BERKO mice between M (53%; P < 0.05) and F (55%; P < 0.05) was abolished. Our comparative proteomic analysis revealed that in WT M and F mice 82 and 31 protein spots, respectively, differed between sham and TAC (P 蠄 0.05). In BERKO M and F mice we found 114 and 87 altered protein spots, respectively (P 蠄 0.05). Among others, trifunctional enzyme subunit family members were repressed in M‐WT‐TAC mice, while cytoskeletal proteins were induced in F‐WT‐TAC mice. On the other hand, heat shock proteins were induced in both M and F‐BERKO‐TAC mice. In conclusion, our study demonstrates that both sex and ERβ influence the proteomic response of the heart to PO.Grant Funding Source: German Research Foundation (DFG, FG 105, GK 754)
Influence of the baroreflex on the evolution of ventriculo arterial coupling (681.3)
Authors: Bras‐Rosario Luis , Nunes Cecilia , Moura Alexandra , Rocha Isabel , Pinto Fausto , Sequeira Adelia 
Published: June 2021

The Baroreflex is a negative feedback mechanism that controls arterial blood pressure, as sensed by the baroreceptors, increasing or decreasing sympathetic and parasympathetic activity to restore arterial blood pressure. It is an important component of arterial blood pressure and circulatory regulation and therefore a fundamental mechanism in the pathogenesis of Hypertension and Congestive Heart Failure, that is further stressed by the multiple therapeutic approaches designed to influence it. As the Baroreflex influences the heart rate, cardiac contractility and vascular resistance, we hypothesised that it must influence the mechanical interaction between the left ventricle and the arterial tree as well as cardiac energy consumption and efficiency.The ventriculoarterial coupling was evaluated on a beat‐per‐beat basis, upon the application of a left‐carotid sinus baroreflex stimulus in rabbits. The left ventricle end‐systolic elastance and arterial elastance were calculated and the coupling ratio was then related to the indexes of cardiac energetics. Upon the application of the baroreflex, the coupling ratio showed an approximately linear increase, attributed to the rise in ventricular elastance. Stroke work and cardiac efficiency both increased, indicating that not only was the stroke work greater, but it was obtained at a lower oxygen cost. The coupling ratio increased indicating that it was moving towards an optimal stroke work.In conclusion the baroreflex is a control mechanism of the cardiovascular system that exerts a feedback modulation on the arterial pressure through a balanced increase in cardiac contractility and arterial input impedance which results in an improvement in ventriculo arterial coupling, mechanical and energetic efficiency.This approach can now be applied to test acute interventions on the circulatory system, including the short term reflexes as mechano reflexes and chemoreflexes, diseases such as myocardial infarction, drug and device therapy.Grant Funding Source: Fundaçao Ciencia e Tecnologia
Blockade of CB1 receptors reveals that elevated medullary endocannabinoids contribute to age‐related impairment of baroreflex sensitivity in Sprague‐Dawley rats (681.4)
Authors: Schaich Chris , Thomas Brian , Grabenauer Megan , Howlett Allyn , Diz Debra 
Published: June 2021

In the solitary tract nucleus (NTS), angiotensin (Ang) II attenuates whereas Ang‐(1‐7) enhances baroreflex sensitivity (BRS) for control of heart rate. Hypertensive (mRen2)27 rats have low medullary Ang‐(1‐7) relative to Ang II associated with impaired BRS that is restored by CB1 receptor blockade in the NTS, consistent with elevated 2‐arachidonylglycerol (2‐AG) in dorsal medulla relative to SD rats. Sprague‐Dawley (SD) rats develop elevated systolic blood pressure as they age, which is associated with impaired BRS resulting from reduced NTS Ang‐(1‐7). We now report that older SD rats exhibit higher 2‐AG at ~70 versus ~15 wks of age (3.9 ± 0.6 vs 1.8 ± 0.3 ng/mg tissue; p < 0.02, n = 4 ‐ 6 each group). Anandamide also tended to be higher in older rats; however, levels were 1000‐fold lower than 2‐AG. Consistent with the elevated endocannabinoids (EC) in dorsal medulla, CB1R antagonist SR141716 (36 pmol/120 nl) microinjection into NTS of older SD rats increased BRS (0.53 ± 0.08 baseline vs 1.06 ± 0.6 msec/mm Hg 60 min after SR141716; p < 0.05, n = 3). In conclusion, elevated ECs within the NTS appear to contribute to the BRS impairment observed in older SD rats.Grant Funding Source: Supported by NIH: P01‐HL51952, R01‐DA03690, and RTI International
Exacerbated α‐adrenoceptor‐mediated vasoconstriction in obese rats during anesthesia (681.8)
Authors: Lamberts Regis , de Leeuw Anne , Bussey Carol 
Published: June 2021

Obese patients undergoing surgery have a higher risk of cardiovascular complications due to an unidentified instability in blood pressure (BP) regulation. The sympathetic nervous system is a crucial BP regulator, acting through α‐ and β‐adrenoreceptors (ARs), and is influenced by anesthesia. Our study aimed to determine how obesity alters cardiovascular AR responsiveness in vivo, and how this is affected by anesthesia.Sixteen week old Male Zucker Obese rats (n=7) and lean littermates (n=7) underwent dual implantation surgery. A radiotelemeter in the abdominal aorta provided mean arterial pressure (MAP) and heart rate (HR), and a vascular access port in the femoral vein provided non‐invasive intravenous access. Animals were injected with incrementing doses of dobutamine (2‐120 µg/kg) or phenylephrine (1‐100µg/kg) to stimulate β‐ or α‐ARs respectively, under conscious and anesthetized (2% isoflurane) conditions.Obese animals displayed a reduced HR increase to β‐AR stimulation under conscious conditions (103±12 vs. 61±9 bpm; p<0.001 at 15µg/kg), which was lost during anesthesia (51±3 vs. 66±5 bpm; NS at 15µg/kg). α‐AR stimulation elicited greater increases in MAP in conscious obese rats (53±5 vs. 70±3 mmHg; p<0.01 at 8µg/kg), an effect that was exacerbated by anesthesia (41±5 vs. 69±4 mmHg; p<0.001 at 8µg/kg). Interstingly, obesity interacted with anesthesia, resulting in a significantly prolonged α‐AR‐mediated elevation in MAP compared to lean animals.Thus, both α‐AR and β‐AR dysfunction are observed in obesity, and are differently affected by anesthesia. The inability of obese patients to appropriately alleviate excess BP during anesthesia may cause undue pressures on the heart and contribute to their perioperative complications.