bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating the Physiological Role of Mitochondrial ETC Supercomplexes in the Heart
Authors: Chapa‐Dubocq Xavier R , Rodriguez‐Graciani Keishla Marie , Guzman‐Hernandez Roberto Alejandro , Jang Sehwan , Javadov Sabzali 
Published: June 2021

BackgroundFor a long time, mitochondrial electron transport chain (ETC) complexes was thought to function as separate entities. However, studies conducted in the past decade revealed that individual ETC complexes can assemble to form supramolecular structures known as supercomplexes (SCs). The SCs, particularly respirasome are composed of the ETC complexes I, III and IV in various stoichiometry. The respirasome is considered to play an important role in facilitating electron transport, reducing ROS production, and maintaining structural integrity of individual ETC complexes. Despite extensive studies on the molecular identity, the physiological role of SCs in cells, particularly, in high energy‐consuming organs such as the heart and brain remain unknown. These studies seek to determine whether disassembly of SCs affects the cardiac function in rats.MethodsHearts isolated from Sprague Dawley rats (275–325g) were perfused with Krebs Henseleit solution (KHS) via the Langendorff‐perfusion model. Experimental groups were as follows: (i) perfusion for 40 min with KHS, (ii) perfusion for 20 min with KHS and 20 min with rotenone (an inducer of SC dissociation) (n=8), (iii) perfusion for 60 min with KHS (n=4), (iv) perfusion for 20 min with KHS followed by 20 min perfusion with rotenone and 20 min with KHS (washout, no rotenone) (n=6). In control groups (i) and (iii), ethanol was as a vehicle in concentration used for rotenone groups [(ii) and (iv)]. In addition, we compared SC levels in mitochondria isolated from non‐perfused hearts (v), and hearts perfused with KHS (vi) containing no vehicle (ethanol) with those in i–iv groups. Cardiac function was monitored throughout the entire perfusion period. At the end of each protocol, the mitochondria were isolated for analysis of SCs, permeability transition pore opening, respiration rates and ROS production.ResultsCardiac function between rats perfused with KHS (vi) and ethanol (i and iii) had no significant difference, though rotenone perfused rats (ii and iv) had a significant reduction (< 40%) in cardiac function. Mitochondrial respiration data shows a significant reduction in complex I oxygen consumption rate in rotenone perfused (ii and iv) rats. Analysis of SCs by blue native PAGE displayed a significant reduction in SC levels in both ethanol (i and iii) and rotenone (ii and iv) perfused rats in comparison to hearts perfused with KHS (vi) alone. No significant differences in SC levels were found between the ethanol (i and iii) and rotenone (ii and iv) perfused groups.ConclusionOur data demonstrate lack of causal relationship link between mitochondrial ETC SCs and cardiac function in rats.Support or Funding InformationSupported by the NIGMS NIH grants SC1GM128210 and R25GM061838This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nonlinear dynamics of heart rate variability during paced breathing: Recurrence quantification analysis of heart rate
Authors: IARDUKHINA IULIIA , Dimitriev Dmitry , Remizova Nadezhda , Dimitriev Aleksei , Saperova Elena 
Published: June 2021

BackgroundRecurrence is a fundamental property of many physiological systems and recurrence plot (RP) with its subsequent quantitative analysis is an effective approach to assessment complexity of physiological signals. The aim of this study is to assess the influence of paced breathing on RP complexity measures of heart rate variability (HRV) in healthy young females.Materials and methodsTwenty‐nine female university students (age 20.4 ± 0.2 years) participated in the study. The subjects breathed spontaneously and following the respiratory pacer for 5 min at each of 5 frequencies: 6.5, 6, 5.5, 5, 4.5 breaths/min. Five‐minute heart rate variability time series were recorded during spontaneous and paced breathing. We computed the following RQA measures: recurrence rate (REC), mean line length (Lmean), maximum line length (Lmax), determinism (DET), and Shannon entropy of line length distribution (ShanEn). Friedman ANOVA and Wilcoxon test were used to determining the significance of differences between measurements. Data are mean±SE.ResultsPaced breathing causes significant increasing of REC from 22.07±0.71 % (free breathing) to 29.53±0.6 % (6.5 breaths/min) (p <0.01). Paced respiratory rate was associated with significant increasing of Lmean from 8.33±0.2 (free breathing) to 17.54±0.94 (6.5 breaths/min) (p <0.01). Lmax was significantly (p < 0.01) higher during paced breathing (6.5 breaths/min – 279.59±14.8, 6 breaths/min – 297.96±12.27, 5.5 breaths/min – 284.09±17.3, 5 breaths/min – 276.14±22.32, 4.5 breaths/min – 228.15±23.53) than during free breathing (71.18±6.77). The statistical analysis showed that in comparison with free breathing, the DET value was significantly higher during paced breathing (p < 0.01): 96.28±0.18 at free breathing, 96.28±0.18 at 6.5 breaths/min, 98.61±0.09 at 6 breaths/min, 98.65±0.09 at 5.5 breaths/min, 98.69±0.18 at 5 breaths/min, 98.28±0.36 at 4.5 breaths/min. ShanEn was significantly (p < 0.01) increased during paced breathing (6.5 breaths/min – 3.35±0.04, 6 breaths/min – 3.3±0.03, 5.5 breaths/min – 3.22±0.03, 5 breaths/min – 3.24±0.06, 4.5 breaths/min – 3.17±0.06) than during free breathing (2.85±0.03). Recurrence indexes showed that the heart rate dynamics during paced breathing are different from free breathing, suggesting a loss of complexity of the heart rate autonomic regulation system.ConclusionsRecurrence quantification analysis of HRV is sensitive to paced breath and might, therefore, be suited to assess interactions between the cardiovascular system and respiration. The loss of HRV complexity might reflect an increased regularity of HR oscillations caused by paced breathing. Thus, RP has the potential to provide supplementary information about the dynamics in heart rate regulation.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Spinal Cord Injury and Chronically Induced Orthostatic Hypotension on Left Ventricular Contractility and Stiffness
Authors: Hayes Brian , Poormasjedi‐Meibod Malihe‐Sedat , Fossey Mary , Erskine Erin , Gupta Rishi , Granville David J , Phillips Aaron A , West Christopher R 
Published: June 2021

IntroductionComplete spinal cord injury (SCI) above the T3 spinal level is associated impaired left ventricular (LV) systolic function. However, the effect on diastolic structure and function has yet to be examined. Furthermore, high thoracic SCI impairs centrally‐derived cardiovascular responses to postural change, leading to the development of orthostatic hypotension (OH) post‐SCI. While it has been demonstrated that these frequent bouts of OH cause impairments in cerebrovascular function, it is not known whether this hemodynamic instability also impairs cardiac function.MethodsThis study examined the effect of SCI on LV systolic and diastolic function in the presence or absence of daily bouts of acutely induced OH. 22 rats were divided into four groups: 1. Rats with a sham injury and no daily OH (SHAM, n=5), 2. Rats with a sham injury and daily induced OH (SHAM‐OH, n=6), 3. Rats with a complete T3 transection injury and daily induced OH (T3‐OH, n=5), 4. Rats with a complete T3 transection and no daily OH (T3‐SCI, n=6). 9 weeks after surgery, LV pressure‐volume (PV) catheterization was performed to assess LV basal PV indices, as well as cardiac contractility and stiffness. Furthermore, the coupling of the arterial system and the left ventricle was characterized to examine the influence of SCI and/or OH on the efficiency of the interaction between the LV and arterial system.ResultsCompared to both SHAM and SHAM‐OH, the T3‐SCI and T3‐OH groups experienced significant reductions in systolic blood pressure, LV stroke work and cardiac output (all p<0.023). The T3‐OH group demonstrated an increase in arterial elastance compared to both the SHAM‐OH and SHAM groups (p<0.014). T3‐SCI and T3‐OH groups exhibited reduced end‐systolic elastance compared to both SHAM and SHAM‐OH (p<0.04). No difference was found in LV stiffness between the four groups. Finally, the ratio of ventricular‐vascular coupling was found to be significantly increased in the T3‐OH group compared to all other groups (all P<0.019).ConclusionComplete high thoracic and cervical SCI causes a reduction in LV contractile function. Combined high thoracic SCI and daily OH impairs ventricular‐vascular coupling via changes in arterial compliance.Support or Funding InformationHeart and Stroke Foundation of Canada (HSFC), International Collaborations on Repair Discoveries (ICORD), Natural Sciences and Engineering Research Council of Canada (NSERC), Blusson Integrated Cures Partnership (BICP).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Revised Pulmonary Artery Constriction Model of Right Ventricle Failure in Adult Ovine
Authors: Nguyen‐Truong Michael , Liu Wenqiang , Boon June , Nelson Brad , Easley Jeremiah , Monnet Eric , Wang Zhijie 
Published: June 2021

IntroductionRight ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients [1]. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models to investigate the pathogenesis that includes biomechanical properties and mechanobiology of the RV [2,3]. In this study, we aim to establish an adult ovine model of RVF to examine the hemodynamic, structural and mechanical adaptations of the RV under chronic pressure overload.MethodsAll procedures were approved by Colorado State University IACUC. To induce RV pressure overload, ~8‐month old male sheep underwent a revised method of pulmonary artery constriction (PAC) by patient‐specific, repeated filling of an adjustable hydraulic occluder (Norfolk Vet Products, IL) with saline at week 0, 1, and 4. The amount of saline injected was determined to acutely elevate the RV pressure to be comparable to its own left ventricle pressure. Healthy, age‐matched male sheep were used as controls (CTL). Echocardiography was performed in awake animals at baseline (week 0) and 2, 4, 6, 8, and 11 weeks post PAC. On week 11, animals were anesthetized and catheterized with Swan‐Ganz and pressure‐volume (PV) catheters to obtain hemodynamic measurements. Finally, hearts were extracted and tissue thickness and weight were measured. RV hypertrophy was quantified by RV wall thickness using a caliper and Fulton's index as the weight of RV/(LV+Septum). One‐way ANOVA with repeated measures and Dunnett's post hoc tests were performed to examine RV changes over time. Unpaired Student's t‐test was performed between the CTL and PAC groups. p<0.05 was considered statistically significant compared to baseline (week 0) or CTL.ResultsThe new PAC methodology resulted in a marked increase in RV systolic pressure (RVSP) and decreases in stroke volume and tricuspid annular plane systolic excursion (TAPSE) at week 11 (Fig. a–c). During the PAC period, impaired ejection dynamics was observed by a gradual decrease of the ratio of acceleration time to ejection time (AT/ET) (Fig. d). Significant increases in Fulton's index and RV free wall thickness suggested RV hypertrophy under PAC (Fig. e–f). The systemic circulation and LV were not affected and functioned normally (data not shown).ConclusionThe revised patient specific, repeated PAC method provided an easy and robust approach to induce RVF secondary to pressure overload. The development of RVF was evident by changes in RV structure and function as described above. The histological and mechanical changes will be further investigated. This ovine model will offer a useful tool to study the progression and treatment of RVF in large animal species.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiac and Renal Function Interactions in Heart Failure with Reduced Ejection Fraction: A Mathematical Modeling Analysis
Authors: Yu Hongtao , Hallow Melissa Karen 
Published: June 2021

Congestive heart failure is characterized by suppressed cardiac output (CO) and arterial filling pressure, leading to renal retention of salt and water, contributing to further volume overload and dysfunction. It remains a challenge to understand or predict the interplay between the heart and kidneys especially when one of them is in a state of dysfunction. Mathematical modeling provides a means to investigate the acute and chronic functional feedback between the organs. In the current work, two mechanistic mathematical models of cardiac and renal function, previously reported separately, were integrated to simulate the physiological relationships between cardiac and renal function. The two models were linked as follows: 1) mean arterial pressure (MAP) and venous pressure determined from the cardiac model serve as input to the renal model, 2) sodium and water excretion in the kidney model determines extracellular fluid volume in the cardiac model, and 3) the exchange of the fluid between the blood volume (BV) and interstitial fluid volume (ISFV) through capillary membrane was considered via starling forces. By adjusting the heart contractility, arterial stiffness, and systemic resistance, the main pathophysiological features of heart failure with reduced ejection fraction (HF‐REF) could be reproduced: decreased ejection fraction, elevated and gradually increasing BV and ISFV, elevated end diastolic pressure of the left ventricle, and loss of cardiac reserve. Quantitatively, agreement with the clinical characteristics of healthy and HF‐REF subjects seemed to support the proposed cardio‐renal model in capturing the physiological features. The cardio‐renal model can also reproduce the improvements in HF‐REF function with Angiotensin‐Converting‐Enzyme inhibitor (ACEi) as reported in the SOLVD clinical trial. This model has the potential to provide insights into the mechanisms by which pharmacologic targets in the kidney alter or improve cardiovascular function in heart failure.Support or Funding InformationThis research was funded by AstraZenecaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ethnic difference in nighttime melatonin can partially explain the ethnic difference in nighttime blood pressure: A study in European Americans and African Americans
Authors: Wang Xiaoling , Zhu Haidong , Harris Ryan , Dong Yanbin , Su Shaoyong , Tingen Martha , Kapuku Gaston , Pollock Jennifer , Pollock David , Harshfield Gregory 
Published: June 2021

BackgroundBlood pressure (BP) follows a diurnal pattern which is regulated by circadian clock. Epidemiological studies have demonstrated that nighttime BP is a stronger predictor of cardiovascular morbidity and mortality compared to daytime BP. Ethnic differences in nighttime BP have long been documented with African Americans (AAs) having higher pressures than European Americans (EAs). Recently, lower nighttime melatonin, a neurohormone in the superachiasmatic nucleus and key regulator of the central circadian clock, has been associated with higher nighttime BP levels in EAs. However, whether or not ethnic difference exists in nighttime melatonin secretion is unknown. This study sought to test the hypothesis that AAs will have a lower nighttime melatonin secretion compared with EAs and this ethnic difference in melatonin can at least partially explain the ethnic difference in nighttime BP.MethodsA total of 150 young adults (71 AA and 79 EA; mean age: 27.7 years old; age range: 20.5–35.9 years old, 46% females) enrolled in visit 15 of the Georgia Stress and Heart study provided an overnight urine sample for the measurement of 6‐sulfatoxymelatonin, the major metabolite of melatonin. Urine melatonin excretion (UME) was calculated as the ratio between 6‐sulfatoxymelatonin concentration and creatinine concentration. Twenty‐four‐hour ambulatory BP was measured in all participants and nighttime systolic BP (SBP) was used as a major outcome of BP regulation.ResultsAfter adjustment of age, sex and body mass index, AAs had significantly lower UME (AAs vs EAs: 0.26±0.20 vs 0.34±0.33; P=0.002) and higher nighttime SBP than EAs (AAs vs EAs: 110.0±10.2 vs 107.2±8.9 mmHg; P=0.036). Lower UME rate was significantly associated with higher nighttime SBP and this relationship did not depend on ethnicity. With a tertile increase in UME, mean nighttime SBP decreased 2.6 mmHg (P‐value for trend=0.011). The ethnicity difference in nighttime SBP was significantly attenuated after adding UME into the model (P for ethnicity=0.193). Mediation testing showed that 35.5% of ethnicity difference in nighttime SBP could be explained by UME (P=0.035).ConclusionThe present study is the first to document the ethnic difference in nighttime melatonin excretion, suggesting that AAs have an impaired circadian rhythm and low melatonin secretion compared with EAs. Furthermore, the ethnic difference in nighttime melatonin can partially explain the established ethnic difference in nighttime SBP.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebrovascular Consequences of Chronic Orthostatic Hypotension
Authors: Suraj Rejitha , Hodge Sarah , Spence Emma E.M. , Walsh Emma J. , Zhu Hai‐Lei , Sutherland Cindy , Turnbull Jeannine , Belke Darrell , Rosentreter Ryan E. , Soriano Jan Elaine , Scott Berkeley A. , Saddiq Ibrahim A. , Cole William C. , West Christopher , Phillips Aaron A. 
Published: June 2021

Population‐level data indicates that people who chronically experience orthostatic hypotension have an elevated risk of cerebrovascular disease. We are unaware of experimental data to support these observations, and the mechanistic underpinnings of this population‐level association are yet to be understood. Here, we aimed to evaluate if chronic exposure to orthostatic hypotension impairs cerebrovascular function and structure.We first developed a rodent model of orthostatic hypotension that resulted in a clinically‐relevant reduction in systolic blood pressure that was accompanied by hypo‐perfusion of the brain. Next, a group of animals were chronically exposed to repetitive orthostatic hypotension for five weeks, while a control group received standard care. Cerebrovascular function and structure were then evaluated using a variety of in vivo and in vitro methods.Our results suggest that chronic exposure to orthostatic hypotension may impair the function and structure of the cerebrovasculature. More work is needed to understand the mechanisms underlying the cerebrovascular consequences of chronic orthostatic hypotension.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Clinical Neurosciences Pilot Research Fund Program, Libin Cardiovascular Institute, Hotchkiss Brain Institute, Compute CanadaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Carbonic Anhydrase II Deletion Confers Salt Appetite and Elicits Adaptive Regulation of Salt and Water Transporters in the Kidney
Authors: Soleimani Manoocher , Kia Mujan Varasteh , Barone Sharon , Brooks Marybeth , Zahedi Kamyar 
Published: June 2021

BackgroundSalt appetite, which is salt craving or salt intake in excess of physiological needs, is regulated by a number of physiological mechanisms including neuronal and hormonal pathways. Excess salt intake is a major health problem and a risk factor for many diseases, including hypertension. Few genetic factors are implicated in the pathogenesis of salt appetite.Methods and ResultsHere we demonstrate that mice with the genetic inactivation of carbonic anhydrase 2 (CAII) display significant salt appetite as judged by their preference for salted water (280 mM NaCl added to the drinking water) over regular tap water, when both options are provided (average daily salted water intake of 2.80 ml in WT and 5.2 ml in CAII KO mice, p<0.01, n=5 while daily tap water intake was 4.2 ml in WT and 2.8 ml in CAII KO mice, p<0.03, n=5). The excess salt intake was observed in the absence of any vascular volume depletion or kidney dysfunction, as judged by comparable kidney renin expression and blood creatinine and BUN concentration levels in WT and CAII KO mice, and was more profound in male mice. When only provided the salted water (280 mM salt added to the drinking water), CAII null animals showed a robust increase in daily water intake vs. WT mice (20.54 ml in KO mice vs. 11.83 ml in WT, p<0.001, n=5) as well as an increase in sodium excretion (0.192 mmol/g in CAII KO vs. 0.0716 mmol/g in WT, p<.01, n=5). The expression levels of kidney sodium and water absorbing channels ENaC and AQP‐2, determined by western blotting and northern hybridization, showed robust increases (ranging from 100 to 200%) in response to enhanced salt intake in CAII KO mice vs. wild type littermates. The AVP expression levels in pituitary gland significantly increased in CAII KO mice vs. WT littermates when receiving salted water for 10 days (p<0.05), despite their comparable expression levels at baseline conditions. We propose that CAII plays an important role in regulating salt intake and its inactivation can cause salt appetite, specifically in male animals.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.