bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic cerebral pressure‐flow relationships in aging and long‐term heart transplant recipients (1068.11)
Authors: Smirl Jonathan , Haykowsky Mark , Marsden Katelyn , Jones Helen , Nelson Michael , Ainslie Philip 
Published: June 2021

Long‐term heart transplant recipients (HTR) provide a unique opportunity to examine the relationship between the cerebrovascular and cardiovascular systems. We examined the hypothesis that HTR would have cerebral pressure‐flow responses more comparable to control subjects matched to the age of their cerebrovasculature than their donor hearts. Eight male clinically stable HTR (62 ± 8 yrs of age and 9 ± 7 yrs post transplant), 9 male age‐matched controls (AM: 63 ± 8 yrs) and 10 male donor controls (DC: 27 ± 5 yrs), were tested. Each test involved: seated rest (5‐min), and squat‐stand maneuvers at 0.05 and 0.10 Hz. The BRS and pressure‐flow responses were assessed with TFA. BRS TFA revealed that the HTR had reductions in R‐R interval PSD and LF gain (P<0.01) compared to both control groups. There were comparable TFA cerebral pressure‐flow responses for all groups at all frequencies with coherence and phase. The pressure‐flow gain was significantly greater in DC than both AM and HTR at all frequencies (P<0.05). Cerebrovascular resistance (CVR) was negatively correlated with pressure‐flow gain at all frequencies (P<0.05). These results reveal that pressure‐flow coherence and phase are comparable throughout aging, potentially helping HTR compensate for reductions in BRS. Although pressure‐flow gain did decrease in the HTR and AM, it was related to changes in CVR highlighting the need cautiously interpret this metric.Grant Funding Source: Supported by NSERC
Cerebral blood flow regulation is affected immediately following a concussion (1068.16)
Authors: Tosto Jenna , Falvo Michael , Reyes Levy , Blatt Melissa , Ghobreal Bemin , Serrador Jorge 
Published: June 2021

A modern health epidemic, mild traumatic brain injury (mTBI) effects between 1.5 and 3.8 million Americans each year. Recent data has shown that concussions can result in long term problems. Despite this, there continues to be difficulty in diagnosing concussion within current technology. The goal of this work was to determine if changes in blood pressure or cerebral blood flow regulation immediately post head trauma could be used as a marker of mTBI. We hypothesized that individuals who sustain an mTBI will exhibit impairments of cerebral blood flow regulation within the first six hours post‐injury, demonstrating concurrent transient physiological and cognitive deficits.Twenty‐six subjects (were recruited during the CanAm Rugby Tournament to participate in an autonomic assessment protocol in which Transcranial Doppler (TCD) was used to assess middle cerebral artery (MCA) blood flow velocity. Heart rate, beat‐by‐beat blood pressure, and end‐tidal CO2 were also measured. Subjects performed three sit to stand maneuvers and a single supine to 60 degree tilt up maneuver.We found that players with concussions showed an impaired ability to reduce cerebrovascular resistance (CVR) when standing (Change in CVR: Concussed +0.6±2.6 vs Controls: ‐4.6±2.1%). Similarly concussed players had longer times to nadir of cerebral flow velocity (Concussed: 7.7±1.0 vs Controls: 6.7±0.7 sec) despite having shorter times to the nadir of blood pressure (Concussed: 7.6±0.5 vs Controls: 7.2±2.2 sec).These data suggest that players with concussions demonstrated impaired cerebral blood flow regulation. This impairment may be a novel indicator of underlying mTBI. Thus, by assessing cerebral blood flow regulation on the field, a better assessment of mTBI may be obtained. Further work is needed to determine if players with impaired cerebral blood flow regulation have long term problems associated with the concussion.
Improving the sensitivity of neurovascular coupling assessment using motor‐cognitive paradigms post‐stroke (1068.4)
Authors: Salinet Angela , Robinson Thompson , Panerai Ronney 
Published: June 2021

Neurovascular coupling (NVC) has been used as an index of synaptic activity in health and disease. Cerebral blood flow velocity (CBFv) responses to neural stimulation can be misleading due to influences from peripheral co‐variates, leading to inaccurate NVC assessment. A dynamic multivariate autoregressive‐moving average (ARMA) model was used to calculate the contributions of blood pressure (BP), PaCO2 and the stimulus itself to changes in CBFv during active (AP), passive (PP) and motor imagery (MIP) paradigms of elbow flexion/ extension. Continuous recordings of CBFv, BP, heart rate and end‐tidal CO2 were performed in 20 stroke patients and 17 control subjects during the three paradigms. Though the paradigms led to a significant bilateral CBFv increase in both groups, differences between stroke and controls were found only during the PP (p=0.02). ARMA analysis revealed a marked BP contribution to the initial peaked CBFv response in both groups during all paradigms, as well as a decrease in the amplitude of the stimulation component after stroke (p<0.001). PaCO2 did not interfere with the CBFv responses during either the MIP in controls or any of the paradigms in the stroke group. However, the responses to AP and MIP in controls were influenced by a significant reduction in PaCO2 (AP reduction of 2%; MIP reduction of 2.5%). By removing the influences of BP and PaCO2, it was possible to detect differences in the effects of stimulation between controls and strokes. We concluded that, independent of the paradigm adopted for NVC assessment, factoring out the influences of BP and PaCO2 can lead to improvements in sensitivity.Grant Funding Source: CAPES ‐ Ministry of Education of Brazil
Dynamic cerebral autoregulation is heterogeneous in different subtypes of acute ischemic stroke (1068.5)
Authors: Guo Zhen‐Ni , Liu Jia , Xing Yingqi , Yang Yi 
Published: June 2021

Dynamic cerebral autoregulation is heterogeneous in different subtypes of acute ischemic stroke Zhen‐Ni Guo1, Jia Liu2, Yingqi Xing1, Yi Yang1* 1Department of Neurology, the First Norman Bethune Hospital of Jilin University, Chang Chun, China; 2Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; Zhen‐Ni Guo and Jia Liu contributed equally to the manuscript. * Correspondence author: Yi Yang1, M.D, PhD, #71 Xinmin Street, 130021, Changchun, China. Telephone: 86‐15843073217; E‐mail: doctor_yangyi@hotmail.com Dynamic cerebral autoregulation (dCA) is affected in acute ischemic stroke. Large‐artery atherosclerosis and small‐artery occlusion are considered as the most common subtypes. However, the underlying mechanisms might be heterogeneous, resulting in varied clinical conditions and outcomes. We therefore investigated the pattern of dCA in these two subtypes using transfer function analysis (TFA).Forty‐one patients with acute unilateral middle cerebral artery (MCA) territory stroke (15 with ipsilateral large‐artery atherosclerosis and 26 with small‐artery occlusion, according to TOAST classification) and 20 healthy volunteers were enrolled. Non‐invasive continuous CBFV and ABP were recorded simultaneously from each subject in supine position for 10 minutes using transcranial Doppler (TCD) on MCA bilaterally and servo‐controlled plethysmograph on the middle finger, respectively. TFA was applied to derive autoregulatory parameters, gain, phase, and slope of step response. The results showed that dCA is impaired ipsilaterally with the affected side in the large‐artery atherosclerosis group, whereas the impairment of dCA in the small‐artery occlusion group is bilateral.We thus concluded that dCA in different subtypes of acute ischemic stroke is heterogeneous, which might be attributed to the varied pathologic changes of vessels.
Cerebral autoregulation, individual variability, and white matter hyperintensity (1069.1)
Authors: Liu Jie , Tseng Benjamin , Khan Muhammad , Tarumi Takashi , Hill Candace , Armstrong Kyle , Mirshams Niki , Hodics Timea , Zhang Rong 
Published: June 2021

Purpose: To assess regional cerebral autoregulation (CA) and its association with white matter hyperintensities (WMH) in older adults.Methods: Twenty‐seven healthy older subjects (13 females, 68 ± 6 yr) underwent fluid‐attenuated inversion recovery MRI to measure WMH. Cerebral blood flow (CBF) in the internal carotid (ICA) and vertebral arteries (VA) was measured using color‐coded duplex ultrasonography. CA was assessed during steady‐state changes in mean arterial pressure (MAP) from ‐11 ± 7% to 21 ± 8% (relative to baseline) and quantified by a linear regression slope between percentage changes in cerebrovascular resistance (CVR=MAP/CBF) and MAP. Multiple linear regression analysis was used to explore the relationship between regional CA and WMH.Results: Substantial individual CA variability was found in both ICA and VA with the regression slopes of CVR to MAP ranged from 0.366 to 2.198 in the ICA and from 0.172 to 3.175 in the VA. CA measured in the VA had a positive correlation (r = 0.741, P < 0.001) with periventricular WMH (PWMH), after adjustment for age, central arterial stiffness, sex and resting blood pressure. Of note, individuals with more PWMH (> 0.3 % intracranial volume) showed a hyper‐reactivity of CA (i.e., a paradoxical reduction in CBF during increases in arterial pressure) at the VA. Interpretation: Large individual CA variability exists in healthy older adults. The association between the hyper‐reactivity of posterior CA and PWMH suggests that the presence of small cerebral vessel disease may lead to hypoperfusion in the posterior cerebral circulation during acute increase in blood pressure.Grant Funding Source: NIH grant R01AG033106‐01 and R01HL102457.
A2A adenosine receptor‐mediated increase in coronary flow is dependent on NADPH oxidase‐derived reactive oxygen species (1071.1)
Authors: Labazi Hicham , Rajamani Uthra , Tilley Stephen L , Ledent Catherine , Mustafa S. Jamal 
Published: June 2021

Adenosine induces an increase in coronary flow (CF) mainly through the activation of both A2A and A2B adenosine receptors (ARs); however, the mechanisms responsible for the regulation of CF are not fully understood. Earlier data from our laboratory showed an interaction between adenosine, NADPH oxidase (NOX) and reactive oxygen species (ROS). We hypothesize that adenosine‐mediated increase in CF is dependent upon NOX activation through A2A but not A2B AR. Concentration response curves to adenosine and the A2A AR selective agonist (CGS‐21680) were performed in isolated perfused hearts from WT, A2A and A2B AR knockouts (A2AKO and A2BKO). Adenosine‐induced dose‐dependent increase in CF was significantly decreased (p<0.05) with pre‐treatment with gp91 ds‐tat (a NOX inhibitor; gp91) or EUK134 (a catalase/superoxide dismutase mimic ; EUK) in both WT (WT: 229.7% ± 6.5 vs. WT+gp91: 178% ± 5.9 and WT: 228.4% ± 7.2 vs. WT+EUK: 178.8% ± 5.5) and A2BKO ( A2BKO: 241.3% ± 9.1 vs. A2BKO+gp91: 191% ± 8.7 and A2BKO: 254% ± 9.3 vs. A2BKO+EUK: 194.4% ± 7.9), but not in A2AKO isolated hearts (P>0.05) (A2AKO: 271.5% ± 17.4 vs. A2AKO+gp91: 240.8% ± 13.6 and A2AKO: 271.2% ± 18.4 vs. A2AKO+EUK: 257.6% ± 15.6). Also, CGS‐21680 caused a concentration‐dependent increase in CF in both WT and A2BKO, but not in A2AKO, which was significantly reduced (P<0.05) using gp91 (WT: 226% ± 8.4 vs. WT+gp91: 191.6% ± 6.6 and A2BKO: 182.6% ± 4.4 vs. A2BKO+gp91: 159.7% ± 4.3). Our data suggest that adenosine‐induced increase in CF through the activation of A2AKO AR is dependent upon NOX activation and ROS generation.Grant Funding Source: Supported by HL 094447, HL 027339 and AI 096139
Attenuated insulin induced dilation in coronary arteries from obesity resistant and obesity prone high fat fed rats (1071.6)
Authors: Oltman Christine , Dake Brian 
Published: June 2021

The purpose of this study was to compare physiologic, metabolic and microvascular complications in obesity resistant (OR) and obesity prone (OP) rats fed a high fat (HF) diet. 8 week old male rats were fed a diet containing 45% kcal saturated fat for 42 weeks. Blood pressure was measured by telemetry. Reactivity of small (75 ‐ 150 μm intraluminal diameter) coronary arteries was evaluated. Body weights were 504±7, 669±25*, 685±8*, and 924±39* grams for OR chow, OR HF, OP chow OP HF rats, respectively. Blood pressure was increased in OP rats on control diet (121.5 ± 4.3mmHg*) and further increased with HF diet (129.7 ± 2.4mmHg*), compared to OR rats on control (98.3 ± 4.3mmHg) or HF diet (99.5 ± 3.1mmHg). Glucose clearance was impaired in high fat fed OR and OP rats. Insulin mediated relaxation of coronary arteries from HF fed OR and OP rats was impaired (% relaxation to 100 ng/ml: OR chow = 37.1 ± 15, OR HF = 4.6 ± 5.3, OP chow = 29.3 ± 6.6 and OP HF = 7.6 ± 2.3). Acetylcholine (ACh)‐mediated relaxation of coronary arteries from HF fed rats was impaired (%relaxation to 10 μM Ach: OR chow=67 ± 10, OR HF = 36±12*, OP chow = 41±8*, and OP HF = 22±6*). Sodium nitroprusside (SNP) responses were not altered. *p<0.05 vs OR chow diet. These studies indicate that HF diet augments metabolic and microvascular complications in obesity prone rats.Grant Funding Source: Supported by VA Merit to Dr. Oltman
Temporal response of monocytes during progressive coronary artery occlusion (1071.7)
Authors: Hakimzadeh Nazanin , van Horssen Pepijn , van Lier Monique , van den Wijngaard Jeroen , Belterman Charly , Coronel Ruben , Piek Jan , Spaan Jos , Verberne Hein , Siebes Maria 
Published: June 2021

Elevated levels of circulating monocytes (MCs) have been correlated with collateral development in coronary artery disease patients. The aim of this study was to employ a model of progressive coronary artery occlusion (CO), in order to compare the temporal response of MC upregulation in the systemic circulation vs. their infiltration into ischemic myocardium.An ameroid constrictor was implanted on the left coronary artery of New Zealand White rabbits (CO after 7‐10 days). Peripheral blood MCs were isolated, fluorescently labelled and administered intravenously, 9 (n=4),16 (n=4) or 28 (n=5) days after surgery. Coronary vessels were perfused with fluorescent cast. Hearts were processed with an imaging cryomicrotome, generating 3D reconstructions of the vascular network and MCs.Peripheral blood MCs increased 83.47±55.18% 9 days after CO surgery, while 16 and 28 days after CO surgery showed 39.96±65.27 and ‐13.82±24.17 % change, respectively. MC subset ratios (classical/non‐classical) showed the largest percentage increase after 16 days CO in peripheral blood. In the myocardium, MC infiltration was localized in the ischemic area, and was highest after 16 days vs. 9 days CO (0.027±0.023 vs. 0.017±0.001 of total heart volume, p<0.05). Collateral connections coincided with MC localization. In conclusion, we note that the temporal MC response in the systemic circulation may differ from that in the myocardium.Grant Funding Source: Supported by the Center for Translational Molecular Medicine (EMINENCE).
Reversion from a high‐fat diet to a prenatal normal diet could delay the incidence of insulin resistance induced by postnatal high fat diet in female offspring (1072.2)
Authors: Keith Benjamin , Zhou Lun , Xie Linglin 
Published: June 2021

Many studies have focused on the adverse effects of prenatal high fat diet (HFD) on offspring development, but few studies are aimed on evaluating how prenatal reversion to regular diet (ND) in obese subjects could affect the offspring high fat diet‐induced obesity (DIO). The female obese mice either continued a high fat diet during pregnancy till the end of lactation (HFD group), or switched from HFD to ND for four weeks and continued on ND during pregnancy till the end of lactation (HFD‐ND group). Offspring from both groups were subjected on HFD for 9 weeks after weaning. By the end of the week 9, we found that prenatal HFD‐ND differentially affects the male and female offspring with a postnatal HFD. This is evidenced by slower weight gain, lower weight of the liver, the subcutaneous and the visceral fat in HFD‐ND female offspring compared to the HFD female offspring, but not in HFD‐ND male offspring vs. HFD male offspring. Only HFD‐ND female offspring failed to develop insulin resistance after nine weeks postnatal HFD. This result was not caused by the differential consumption of male and female offspring via evaluating the food consumption. We further found that the female HFD offspring developed inflammation in liver tissue marked by increased macrophage infiltration comparing to the HFD‐ND female offspring. Our results demonstrated that maternal reversion from a HFD to a ND could affect the onset of DIO in female offspring.Grant Funding Source: Supported by the University of North Dakota faculty seed money
Impaired autonomic regulation in hyperglycemia and cardiovascular dynamics during autologous blood donation (1072.7)
Authors: Kamakura Miho , Kanno Emi , Takahashi Masako , Maruyama Ryoko 
Published: June 2021

Hyperglycemia has been reported as a risk factor for autonomic dysfunction. However, the changes in autonomic nerve activity that occur in hyperglycemic patients during blood volume reduction are unclear. This study aimed to investigate the impact of hyperglycemia (HbA1c 蠅 6.5%) on autonomic nerve activity and cardiovascular dynamics during blood volume reduction (300‐400 mL), by using autologous blood donation as a model of mild blood loss.We compared the impact of hyperglycemia and non‐hyperglycemia on heart rate variability, including circulatory regulation, in 17 patients (mean age 60.9 ± 13.6 years) with no circulatory, respiratory, or cranial nerve disease.During autologous blood donation, none of the patients experienced significant changes in blood pressure or heart rate. In non‐hyperglycemia, the low frequency/high frequency component ratio (LF/HF) significantly increased (p < 0.05) and HF decreased during autologous blood donation. In hyperglycemia, LF/HF and HF responses were lower than in non‐hyperglycemia.These results show that hyperglycemia impaired autonomic regulation during a blood volume reduction of approximately 10% of the circulatory blood volume. This suggests that circulatory failure may be more common in hyperglycemic patients than in non‐hyperglycemic patients during moderate or severe blood volume reduction.
From pre‐clinical data to the clinics: identification of circulating inflammatory mediators as potential biomarkers for heart failure (1073.6)
Authors: Altara Raffaele 
Published: June 2021

Inflammatory mediators (IMs) play a pivotal role during cardiac remodeling. In our study we focused on circulating IMs which might be used as biomarkers.In rodents with cardiac hypertrophy and permanent myocardial ischemia we showed a circulating inflammatory profile with a common increase of 4 IMs in the onset of heart failure (HF).To translate this finding to human HF, we established the baseline values of these IMs in healthy people. Thirty healthy volunteers were selected with no known inflammatory condition. Via a membrane‐based assay, we observed no consistent differences for ~40 inflammatory analytes among gender, sample type and time of collection. Thus, we proceeded to determine the circulating IMs in an age‐matched cohort of 30 HF patients.Interestingly, two of the four IMs from our animal models had higher concentrations in HF patients when compared to healthy controls. Besides, these IMs have never been investigated in this setting before. Furthermore, a principal component analysis of the two groups (controls + HF patients) illustrated that one of the IMs was optimally separating the two groups on the base of component 1.In conclusion, the two IMs discovered in pre‐clinics are upregulated in HF patients. Although this first set of results originates from a relatively small sample size, it is particularly encouraging that they might be biomarker candidates for prognostics and diagnostics of HF.Grant Funding Source: Supported by the CTMM and the Dutch Heart Foundation (TRIUMPH).
Suppressor of cytokine signaling 3 exerts divergent local vs systemic effects in angiotensin II‐induced endothelial dysfunction (1074.6)
Authors: Li Ying , Kinzenbaw Dale , Modrick Marry , Faraci Frank 
Published: June 2021

Angiotensin II (Ang II) plays a major role in vascular disease and hypertension, in part, through the interleukin‐6/STAT3 pathway. Pharmacological and genetic methods were used to investigate the role of SOCS3, a negative regulator of STAT3, in vascular disease. To examine direct effects of Ang II, we incubated carotid arteries for 22 hrs, then examined endothelial function using acetylcholine (Ach). Relaxation to Ach was similar in all arteries incubated with vehicle. A low concentration of Ang II (1 nmol/L) did not affect Ach‐induced vasodilation in wild‐type (WT) mice, but reduced that of SOCS3 haplodeficient (SOCS3+/‐) mice by ~50% (P<0.05). This Ang II‐induced impairment was prevented by inhibitors of STAT3, IL‐6, NF‐κB, or a scavenger of superoxide. Responses to nitroprusside were similar in all groups. Ang II type 1 receptor (AT1R) mRNA levels were increased ~2 fold in SOCS3+/‐ mice. In an in vivo model of Ang II‐dependent hypertension, systemic Ang II (1.4 mg/kg per day) infusion for 14 days reduced Ach‐induced vasodilation in both carotid and resistance arteries in brain from WT mice by ~60% (p<0.05). Surprisingly, deficiency in SOCS3 prevented the majority of Ang II‐induced endothelial dysfunction in both vessels, without affecting the pressor response to Ang II. These data suggest SOCS3 plays a divergent role in local versus systemic effects of Ang II on endothelial function.Grant Funding Source: supported by the NIH (HL‐62984, and HL‐113863), the Department of Veterans Affairs (BX001399), and t
Increased Ca2+‐activated Ca2+ influx and impaired Ca2+ buffering in coronary smooth muscle from metabolic syndrome Ossabaw swine (1076.2)
Authors: McKenney Mikaela , Dineen Stacey , Noblet Jill , Tune Johnathan , Sturek Michael 
Published: June 2021

Coronary smooth muscle (CSM) phenotype is affected by intracellular Ca2+ regulation and we have previously correlated changes in CSM Ca2+ signaling from Ossabaw swine with varying stages of coronary artery disease (CAD). Ossabaw swine are a model of metabolic syndrome (MetS) and CAD. Three year old pigs were fed an excess‐calorie, atherogenic or control diet for 6 months. CAD progression, coronary artery function, and CSM Ca2+ signaling were assessed. MetS coronaries had advanced, lipid‐laden atherosclerotic lesions containing calcium deposits, while lean had no CAD. In isometric tension studies diseased coronary rings generated significantly less tension than healthy rings in response to depolarization with 20 mM K+. CSM were enzymatically isolated and loaded with the Ca2+ indicator, fura‐2 AM. Diseased CSM showed less K+‐induced Ca2+ influx compared to healthy cells. Diseased cells recovered less from the cytosolic Ca2+ increase back to baseline, suggesting impaired Ca2+ buffering. In physiologic salt solution (PSS), there was no difference in peak Ca2+ transient elicited by caffeine‐induced intracellular Ca2+ store release. The caffeine‐induced Ca2+ transient in Ca2+‐free PSS, which represents exclusively sarcoplasmic reticulum (SR) Ca2+ release, was decreased in diseased cells. Taken together, these data suggest that lesser SR Ca2+ release elicited greater Ca2+‐activated Ca2+ influx in diseased CSM. After caffeine challenge healthy CSM buffered Ca2+ significantly below basal Ca2+ compared to diseased CSM. Overall, the data suggest impaired CSM SR Ca2+ buffering, decreased SR Ca2+ store, and increased Ca2+‐activated Ca2+ influx in CAD.Grant Funding Source: Supported by NIH HL062552, HL092245, NIH/NCATS CTSI TL1 TR000162