bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Arterial Baroreflex ‐ Muscle Metaboreflex Interaction in Heart Failure
Authors: Kaur Jasdeep , Senador Danielle , Krishnan Abhinav C. , Alvarez Alberto , Hanna Hanna W. , O'Leary Donal S. 
Published: November 2023

Previous studies have shown that heart failure (HF) alters the strength and mechanisms of both the muscle metaboreflex and the arterial baroreflex during dynamic exercise. Muscle metaboreflex activation (MMA) in normal individuals increases mean arterial pressure (MAP) virtually solely by an increase in cardiac output (CO) whereas in HF, the mechanisms of this pressor response shift to peripheral vasoconstriction. In contrast, the pressor response evoked by baroreceptor unloading in normal subjects occurs primarily through peripheral vasoconstriction which is blunted in HF. How HF alters the interaction between these two powerful reflexes when activated simultaneously is unknown. We hypothesized that co‐activation of both reflexes in HF would cause a smaller increase in MAP and a larger vasoconstriction of the ischemic hindlimb vasculature, resulting in an attenuated restoration of blood flow to the ischemic muscle than that observed prior to HF. We activated the muscle metaboreflex in chronically instrumented canines during mild exercise (via graded reductions in hindlimb blood flow; HLBF) followed by baroreceptor unloading (via bilateral carotid occlusion; BCO) before and after induction of HF in the same animals. We observed that interaction between the two reflexes in normal animals is intimately dependent on the hemodynamic parameter investigated; MAP, conductance of all vascular beds except hindlimbs, and ventricular function all exhibited additive interaction, CO and renal conductance demonstrated occlusive interaction while HR exhibited facilitative interaction. Furthermore, BCO during MMA caused a preferentially larger vasoconstriction in non‐ischemic vascular beds, thereby redirecting blood flow to the ischemic vascular bed. However, after induction of HF, all cardiovascular responses except ventricular function exhibited occlusive interaction in response to baroreceptor unloading during MMA. The pressor response during co‐activation of reflexes occurred via substantial vasoconstriction of all vascular beds including the ischemic active muscle and there is no significant restoration of blood flow to the ischemic vascular bed. We conclude that larger vasoconstriction of ischemic active skeletal muscle during co‐activation of both reflexes in HF attenuates the restoration of blood flow to ischemic muscle.Support or Funding InformationHL‐55473 and HL‐126706
Increased CVD Risk Burden Diminishes the Protective Effect of Remote Ischemic Preconditioning Against Endothelial Ischemia‐Reperfusion Injury in Humans
Authors: Van Guilder Gary P. , Trachte Tiffany 
Published: November 2023

PurposeA powerful treatment against endothelial ischemia‐reperfusion injury is remote ischemic preconditioning, which can trigger tissue protection by exposing a limb to small cycles of vascular occlusion. However, animal models of aging, diabetes, hyperlipidemia, and obesity indicate that the protective benefits of ischemic preconditioning are weakened. The extent to which a clinically relevant burden of CVD risk factors interferes with remote preconditioning in humans is not clear. The purpose of the present study was to determine the influence of CVD risk factor burden on the capacity of remote ischemic preconditioning to prevent endothelial reperfusion injury in adults.MethodsTwenty‐two (age: 45±14 yr) sedentary adults (12 lower burden: 0–2 risk factors; <1% 10‐year FRS; 10 raised burden: 3–5 risk factors: ≥1% 10‐year FRS) were studied using a 2×2 randomized cross‐over design. Digital arterial tonometry (EndoPAT 2000, Itamar Medical Inc.) was used to assess endothelial vasodilation during reactive hyperemia before and after 65 min of left arm endothelial ischemia‐reperfusion injury (20 min brachial artery ischemia followed by 45 min reperfusion) that was preceded by remote ischemic preconditioning (right arm brachial artery: 3×5 min ischemia/reperfusion) or sham. Experiments were conducted in accordance with the Declaration of Helsinki for protection of human subjects.Statistical AnalysisRepeated measures ANOVA was used to assess group differences between the reactive hyperemia index (RHI) before and after endothelial reperfusion injury in the absence and presence of remote ischemic preconditioning.ResultsIn lower burden subjects, remote preconditioning was able to prevent endothelial reperfusion injury (from baseline: 2.1±0.4 to post endothelial injury: 2.5±0.5, P=0.072). In contrast, in the raised burden subjects the RHI (baseline: 2.3±0.9) was significantly reduced by 25% despite attempts to induce protection by remote preconditioning (1.8±0.7; P<0.05). The capacity of remote ischemic preconditioning to protect against endothelial reperfusion injury was inversely related (r=−0.61; P=0.004) to CVD risk burden.ConclusionsEndothelial reperfusion injury was prevented when preceded by remote ischemic preconditioning in the lower burden subjects but failed to provide protection in the raised risk burden subjects. CVD risk factors appear to disrupt the protective properties of remote ischemic preconditioning in humans. These findings provide important critical insight to explain why the large‐scale multi‐center RIPHeart and ERICCA randomized trials of remote ischemic preconditioning failed to show reductions in postoperative clinical events in patients undergoing elective cardiac surgery.
Longitudinal Strain by Speckle Tracking Imaging Detected Regional Myocardial Dysfunction in a Rat Model of Ischemia‐Reperfusion
Authors: Omoto Ana Carolina Mieko , Gava Fábio Nelson , Silva Hadder Batista , de Oliveira Mauro , Silva Carlos Alberto Aguiar , Salgado Helio Cesar , Fazan Rubens 
Published: November 2023

The reperfusion therapy after acute myocardial infarction is frequently used for improving coronary blood flow. However, it is known that in long term, reperfused patients may develop heart failure. Echocardiographic follow‐up of reperfused patients has been important to detect cardiac abnormalities. Particularly, strain by speckle tracking has been an echocardiographic approach able to early detect areas of myocardial dysfunction. The aim of this study was to evaluate the endocardial longitudinal strain by speckle tracking in rats submitted to ischemia‐reperfusion (IR). IR consisted of ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion. Male Wistar rats were subjected by IR (N=12) or fictitious sham procedure (control, N=9) and were evaluated by echocardiography, under ketamine and xylazine (50mg/kg, 10mg/kg i.p.) anesthesia, after 4 weeks. Echocardiographic videos were obtained in the long axis, with later application of the software analysis of Strain (VevoStrain™ software, Vevo 2100, Visual Sonics) and calculation of the ejection fraction (EF), end‐systolic volume (ESV) and end‐diastolic volume (EDV), on bidimensional mode. The analysis of six myocardial segments revealed difference between groups only on basal anterior region (IR: −12.9 ± 1.8%, control: −17.8 ± 1.3%), and no difference on the other segments: basal posterior (IR: −15.9 ± 3.5%, control: −15.3 ± 2.6%); mid‐posterior (IR: −21.7 ± 3.3%, control: −22.6 ± 2.6%); apical posterior (IR: −23.9 ± 4.2%, control: −25.4 ± 2.8); mid‐anterior (IR: −9.5 ± 1.8%, control: −14.1 ± 2.8%); apical anterior (IR: −16.5 ± 3.3% control: −18.3± 1.6%). There was a reduction in the ejection fraction and an increase in the end‐systolic volume in the IR group (EF: 58.2 ± 4%, ESV: 303.2 ± 46uL) when compared with control group (EF: 74.6 ± 2%, ESV: 133.8 ± 18.7uL). There was no difference in the end‐diastolic volume (IR: 688.7 ± 56.5uL, control: 579 ± 53.7uL). In conclusion, it was found that the evaluation of strain by speckle tracking in a rat model of IR was useful for detecting regional abnormalities in myocardial deformation (as seen in basal anterior region). Future investigations using this technique before four weeks would be important to detect early abnormalities through the speckle tracking in reperfused ischemic myocardium.Support or Funding InformationFAPESP and CNPq.
Sympathetic Function During Whole‐Body Cooling is Altered in Hypertensive Adults
Authors: Greaney Jody L , Kenney W. Larry , Alexander Lacy M. 
Published: November 2023

Acute cold exposure activates the sympathetic nervous system and elicits a robust systemic pressor response. In hypertensive adults (HTN), cardiovascular‐related morbidity and mortality peak during cold winter months; however, the mechanisms underlying this association are not well defined. We hypothesized that whole‐body cold stress would evoke exaggerated increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in HTN compared to normotensive adults (NTN). MSNA (peroneal microneurography), beat‐to‐beat BP (Finometer), and heart rate (HR; ECG) were measured continuously in 10 NTN (6 M/4 W; age 53±3 yrs; resting BP 125±3/79±1 mmHg) and 10 HTN (5 M/5 W; age 57±2 yrs; resting BP 149±6/88±3 mmHg) during whole‐body cooling‐induced reductions in mean skin temperature (Tsk; water‐perfused suit) from 34.0 to 30.5°C. MSNA at 34.0°C was not different between groups (NTN: 51±4 v. HTN: 54±5 bursts· (100 heartbeats)−1; P=0.71). During cooling, the increase in MSNA was exaggerated in HTN (NTN: Δ = 8±3, HTN: Δ = 19±3 bursts· (100 heartbeats)−1; P=0.02). The cooling‐induced increases in both systolic BP (NTN: 9±3, HTN: 19±3 mmHg; P=0.03) and mean arterial pressure (NTN: 6±2, HTN: 10±2 mmHg; P=0.08) were greater in HTN. The HR response to cooling was not different between groups (P=0.16). The slope of the relation between MSNA burst incidence and diastolic BP did not change during cold stress in NTN (Tsk = 34.0°C: ‐4.0±0.7 v. Tsk = 30.5°C: ‐5.0±0.3 bursts· (100 heartbeats)−1·mmHg−1; P=0.17) but increased in HTN (Tsk = 34.0°C: ‐2.9±0.5, Tsk = 30.5°C: ‐5.0±0.4 bursts· (100 heartbeats)−1·mmHg−1; P=0.04). These data demonstrate that the whole‐body cooling‐induced increases in MSNA and BP are augmented in HTN. Further, sympathetic baroreflex sensitivity increases during cooling in HTN, but not NTN, presumably to allow for baroreflex‐mediated buffering of excessive cooling‐induced increases in BP. Collectively, these findings suggest that sympathetic function during cold stress is altered in human hypertension, likely contributing to increased cold‐associated cardiovascular risk.Support or Funding InformationHL093238 (LMA) and HL120471 (JLG)
Modulation by NADPH‐ox/Rho‐kinase signaling of the cyclosporine‐NSAIDs interactions on blood pressure and baroreflexes in female rats
Authors: El‐Mas Mahmoud M , Ibrahim Karim S , El‐Yazbi Ahmed F , El‐Gowelli Hanan M 
Published: November 2023

The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these adverse effects of CSA are influenced by co‐administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH‐ox/Rho‐kinase pathway mediates this interaction. Female rats were treated for 10 days with CSA (25 mg/kg/day), diclofenac (DIC, COX‐1/COX‐2 inhibitor, 1 mg/kg/day), celecoxib (COX‐2 inhibitor, 10 mg/kg/day), or their combinations. Baroreflex curves relating changes in heart rate (HR) to increases or decreases in blood pressure (BP) evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), respectively, were constructed and slopes of the curve were taken as measures of BRS. Compared with control rats, CSA increased BP and reduced reflex chronotropic responses as indicated by the significantly smaller BRSPE and BRSSNP. Similar effects were observed in rats treated with diclofenac alone or combined with CSA. Whereas CSA hypertension was maintained after COX‐2 inhibition (celecoxib), the concomitant BRS reductions were largely eliminated. NADPH‐ ox inhibition by diphenyleneiodonium blunted the CSA/DIC‐evoked increases and decreases in BP and BRSPE, respectively. By contrast, fasudil (Rho‐kinase inhibitor) had no effect on CSA/DIC hypertension but reversed the associated reductions in both BRSPE and BRSSNP. Cardiac NADPH oxidase II (NOXII), but not Rho kinase (ROKII), protein expression was increased in CSA/diclofenac‐treated rats and this effect disappeared after co‐administration of fasudil or DPI. Together, depending on the nature of the cardiovascular response, NADPH‐ox and Rho‐kinase contribute variably to the worsened cardiovascular profile in CSA/DIC‐treated rats. Further, celecoxib rather than diclofenac could be a better choice as an add‐on therapy to CSA in autoimmune arthritic conditions.Support or Funding InformationSupported by the ALEX‐REP Grant Fund, Alexandria University, Egypt (Grant HLTH‐13‐01).
Disorder of Renin‐Angiotensin System Promoting the Acute Pulmonary Inflammation by Particulate Matter 2.5 (PM2.5) Exposure
Authors: Lin Chung‐I , Wang Guan‐Hua , Cho Ching‐Chang , Wu Hsi Tien , Hsieh Wen‐Yeh , Lin Chih‐Sheng 
Published: November 2023

Acute or chronic particulate matter 2.5 (PM2.5) exposure can induce oxidative stress, inflammation and pulmonary impairment by traversing the blood‐air barrier of alveolar and then depositing at lung. In the present study, we tested whether the pulmonary inflammation and impairment induced by PM2.5 exposure are related to the disorder of pulmonary renin‐angiotensin system (RAS).In this study, we collected PM2.5 from waste gas which was produced from vehicle engine, and determined the component elements and structures of the PM2.5. The C57BL/6J (wild type, WT) mice and angiotensin converting enzyme II (ACE2) gene knockout (ACE2KO) mice were treated with the PM2.5 by intratracheal instillation once a day for a total of 3 days, and then sacrificed at the 4th day. Lung tissue of the mice was collected for the assays of molecular, biochemical and pathological changes to evaluate the acute pulmonary inflammation and lung injury induced by PM2.5 exposure.The results indicated that the most of collected particulates in this study were aggregated and parts of them formed structure of chains below 2.5 μm diameter. The major compositions of the PM2.5 are carbon and oxide, and contain little silicon, sulfate and copper. The body weight of both WT and ACE2 KO mice treated with PM2.5 was decreased and resting breathing rate was significantly increased. PM2.5 treatment induced pathological leukocyte infiltration in the lung, increased pulmonary immunocytokines concentration, including interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNF‐α) and tumor growth factor beta 1 (TGF‐β1), and also promoted signaling protein ERK1/2 and STAT3 phosphorylation. The quantitative data showed that the levels of physiopathology and inflammation induced by PM2.5 were serious in the ACE2 KO mice compared with those in the WT mice. PM2.5 treatment significantly increased pulmonary ACE expression and activity in both WT and ACE2 KO mice. Interestingly, pulmonary ACE2 activity in the WT mice was also induced. We hypothesized that increased ACE2 activity in the WT mice is a physiological response for increased ACE activity due to PM2.5 exposure. However, the response is lack in the ACE2 KO mice because the mice being ACE2 deficiency. It is one of the reasons that serious physiopathology and inflammation induced by PM2.5 in the ACE2 KO mice compared with those in the WT mice.Our data reveals that acute inflammation and lung injury could be induced by PM2.5 treatment. The disorder of pulmonary RAS may aggravate the disease progressive of pulmonary system due to PM2.5 exposure. Therefore, we propose that it may be helpful for the cardiopulmonary patients by RAS regulation when the patients are exposed to severe particulate pollutants.
Characterisation of a Mouse Kidney Cortical Collecting Duct Cell Line Suggests Plasticity Between Cell Types
Authors: Assmus Adrienne M , Mansley Morag K , Mullins Linda J , Peter Audrey , Mullins John J 
Published: November 2023

The kidney collecting duct is composed of principal (PC) and intercalated (IC) cells responsible for the reabsorption of water and sodium, and the acid‐base balance, respectively. The immortalized mCCDcl1 cell line is widely used as a model for PCs since cells respond to glucocorticoid (MR) and mineralocorticoid (MR) hormones, such as aldosterone, and give reproducible electrophysiological responses.The effect of culture media on sodium transport in the mCCDcl1 cell line was tested by electrophysiological methods and immunostaining. The cells were cultured on filters in two media: the original medium published by Gaeggeler et al.(2005), and an alternative medium using a different source of sodium selenite supplement (Gibco). The cells transepithelial voltage and resistance across monolayers of cells was measured using an epithelial volt‐ohm‐meter, allowing calculation of the equivalent short circuit current by Ohm's law. Basal currents recorded from cells cultured in the original medium measured −9.97μA/cm2, were amiloride‐sensitive and stimulated by ~2.6 fold following aldosterone treatment (−26.78μA/cm2). Cells cultured in the alternative medium exhibited negligible current and no response to aldosterone was observed.Immunostaining was performed in the alternative media on the mCCDcl1 cells and on isolated subclones using antibodies against PC and IC markers: Aquaporin 2 (Aqp2) and the alpha subunit of the epithelial sodium channel (α‐ENaC) for PC, Connexin 30 (Cx30) and vacuolar H+ ATPase (V‐ATPase) for IC. Both the original cell line and the clonal sub‐lines exhibited varied expression of Aqp2 and Cx30, with evidence of co‐expression in sub‐populations of cells. 41.8% of cells from the parental sub‐line express both PC and IC markers whilst 23.8 to 58.7% cells in the clonal sub‐lines express both PC and IC markers. Expression of both PC and IC markers was confirmed by PCR analyses, and RNA sequencing. Immunostaining for α‐ENaC revealed staining across the apical membrane of the cells when cultured in the original medium and perinuclear staining when cells were cultured in the alternative medium.These results show that the provenance of the culture media supplements has a direct consequence on the phenotype of the cells and correlates with their capacity for sodium transport. Secondly, mCCDcl1 cells can present characteristics of both principal and intercalated cells and may have the capacity to switch between the two phenotypes.Support or Funding InformationBritish Heart Foundation Center of Research Excellence PhD Studentship
Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla (RVM) in inflammatory pain
Authors: Li Minghua , Suchland Katherine L , Ingram Susan L 
Published: November 2023

The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM but it is not known if this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature inhibitory postsynaptic currents (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA‐treated rats compared to naïve rats. The reduction in CFA‐treated rats correlated with decreased CB1 receptor protein expression and function in the RVM. Paradoxically, the non‐selective CB1/CB2 receptor agonist WIN55,212 inhibited GABAergic mIPSCs in both naïve and CFA‐treated rats. However, WIN55,212 inhibition was reversed by the CB1 receptor antagonist rimonabant in naïve rats but not in CFA‐treated rats. WIN55,212‐mediated inhibition in CFA‐treated rats was blocked by the CB2 receptor‐selective antagonist SR144528 indicating that CB2 receptor function in the RVM is increased during persistent inflammation. Consistent with these results, CB2 receptor agonists, AM1241 and GW405833 inhibited GABAergic mIPSC frequency only in CFA‐treated rats and the inhibition was reversed with SR144258. When administered alone, SR144528 and another CB2 receptor‐selective antagonist AM630 increased mIPSC frequency in the RVM of CFA‐treated rats indicating that CB2 receptors are tonically activated by endocannabinoids. Our data provide evidence that CB2 receptor function emerges in the RVM in persistent inflammation and that selective CB2 receptor agonists may be useful for treatment of persistent inflammatory pain.Support or Funding InformationThese studies were supported by the grants from NIH (DA035316 and R56NS093894), and America Heart Association (13SDG14590005, MH.L.).
Does Mozart's music have a relaxation effect?
Authors: Hoshi Junko , Sasaki Mako , Sugawara Misaki , Yang Hongxia , Bao Sarina , Tannno Hiromasa , Kanno Emi , Maruyama Ryoko 
Published: November 2023

BackgroundPrevious studies have suggested that Mozart's music has a relaxation effect. In contrast, several studies have also reported that Mozart's music has an effect on enhancing the ability to focus. There is currently no consistent evidence demonstrating the effects of Mozart's music.ObjectiveThe purpose of this study was to evaluate the effects of Eine Kleine Nachatmusik (K.525), a piece representative of Mozart's music, on heart rate (HR), blood pressure (BP), and autonomic nerve activity.MethodWe performed electrocardiographic (ECG) measurements in 15 healthy young Japanese adults, aged between 19 and 24 years. None of the participants had received a specialized music education. We investigated BP and heart rate variability (HRV) in a resting state, when taking a reading‐span‐test (RST), and when listening to music. We used high frequency (HF, 0.15–0.40 Hz) components as an index of parasympathetic nerve activity and the ratio of low frequency (LF, 0.04–0.15 Hz) to HF components (LF/HF) as an index of sympathetic nerve activity. After 5 minutes at rest, a reading‐span‐test (RST) was used to place a load on participants. Then, participants used headphones to listen to K.525 and a favorite song chosen from 6 pieces of popular Japanese music in randomized order. Both K.525 and the chosen favorite song were approximately 6 minutes long. After listening to music, ECG measurement continued for 5 minutes. All data are expressed as mean ± SE. One‐way repeated‐measures ANOVA and multiple comparison tests were performed to compare each index. A value of P < 0.05 was considered significant.ResultsThere was a significant decrease in HR but no significant changes in BP or LF/HF after listening to both K.525 and the favorite song. HF showed a significant increase when listening to the favorite song, whereas K.525 had no notable effect.ConclusionWe found that Mozart's music has no relaxation effect. We suggest that a favorite song has a greater activation effect on parasympathetic nerve activity.Support or Funding InformationThis work was supported, in part, by a Grant‐in‐aid for Scientific Research (B) (25305018) from the Japan Society for the Promotion of Science.