bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of lactate on intermediary metabolites expression and mitochondrial biogenesis in perfused hearts (864.5)
Authors: Gabriel‐Costa Daniele , Cunha Telma , Bechara Luiz Roberto , Barreto‐Chaves Maria Luiza , Brum Patricia 
Published: June 2021

The aim of this study was to investigate whether lactate would modulates the expression of genes and proteins related to intermediary metabolism and mitochondrial biogenesis, and its impact on cardiac hemodynamic function. The hearts excised from male healthy rats were perfused with or without lactate (20mM) in Krebs‐Henseleit solution along 120 min in a Langendorff apparatus. Hemodynamic values including of perfusion pressure (PP) were acquired during the experiment. PPARδ, PGC1‐α, COXIV, MCT1, MCT4 and LDH mRNA levels were quantified by real time RT‐PCR. Mitochondrial DNA replication was evaluated, comparing COXII mRNA levels, a specific mitochondrial gene.Protein expression was assessed by Western Blot. The activity of hexokinase, lactate dehydrogenase, pyruvate dehydrogenase, citrate synthase, superoxide dismutase (SOD) and catalase were analyzed by colorimetry and spectrophotometry. Significant differences were accepted when P□0.05. The lactate concentration in the heart tissue was elevated in lactate group at 120 min (1.5 ± 1.2 vs. 4.8 ± 0.7 mM). This response was paralleled by a significant increase in mRNA levels of PPARδ (2.3x), PGC1‐α (4.5x), MCT1 (8.0x), MCT4 (4.0x) and LDH (13.7x) when compared to control group. No differences were observed in mitochondrial DNA replication, COX IV mRNA levels and activity of all enzymes, excepted for SOD that was significantly increased in lactate (26.6 ± 12.1 vs 92.3 ± 25.7 µmol/mg/min). PP value reduced after lactate perfusion (74.2 ± 10.3 vs 27.8 ± 6.8 mmHg). Our results provide evidence that lactate up‐regulates the expression of genes involved in cardiac bioenergetics and mitochondrial biogenesis, which might favor cardiac oxygenation.Grant Funding Source: FAPESP
Early life exposure to air pollution induces adult cardiovascular dysfunction in mice (864.9)
Authors: Velten Markus , Gorr Matthew , Nelin Timothy , Wold Loren 
Published: June 2021

The developing fetus is affected by exposure to air pollutants. We hypothesized that intrauterine and postnatal exposure to air pollutants results in cardiac dysfunction. FVB mice were exposed to ambient particles <2.5 μM (PM2.5) or filtered air (FA) beginning at plug confirmation till weaning. Echocardiography, PV‐loops, cardiomyocyte contractility, and molecular analyses were performed at 10 wks of age. Birth weight was lower in PM2.5 exposed pups (1.36 g ± 0.12 FA vs. 1.30 ± 0.16 PM2.5, P=0.03). Echocardiography revealed reduced FS (43.6 % ± 2.1 FA vs. 33.2 % ± 1.6 PM2.5, P=0.001) and PV‐loops a reduced EF (79.1 % ± 3.5 FA vs. 35.5 % ± 9.5 PM2.5, P=0.005), increased ESV (10.4 µl ± 2.5 FA vs. 39.5 µl ± 3.8 µl PM2.5, P=0.001), reduced dp/dt max (11605 ± 200 FA vs. 9569 ± 800 PM2.5, P=0.05) and min (‐9203 ± 235 FA vs. ‐7045 ± 189 PM2.5, P=0.0005) in PM2.5 exposed mice. Isolated cardiomyocytes had reduced peak shortening (%PS, 8.53 ± 2.82 FA vs. 6.82 ± 2.04 PM2.5, P= 0.003) and lengthened calcium reuptake (0.22 s ± 0.09 FA vs. 0.26 ± 0.07 PM2.5, P= 0.048), coupled with reduced contractile reserve. Histological analyses revealed lower PicroSirius‐red stained areas in the PM2.5 group (0.55 % ± 0.09 FA, 0.55 % ± 0.09 PM2.5, P=0.0003). Our study indicated that developmental exposure to PM2.5 results in a heart failure phenotype at adulthood. This study supports the hypothesis that perinatal insults contribute to cardiac disease during adulthood.Grant Funding Source: Supported by NIH
Cardiac regenerative capacity of the American alligator (87.5)
Authors: Yang Johnny , Owerkowicz Tomasz , Elsey Ruth , Lien Ching‐Ling 
Published: June 2021

Human hearts lack regenerative capacity and form scars after myocardial infarction. While teleost fish and urodele amphibians are able replace lost or damaged cardiomyocytes even as adults, mice are only able do so as neonates. Whether regenerative capacity exists in other vertebrate clades (reptiles and birds) has not yet been described. In order to determine if reptile hearts have regenerative potential following tissue damage, we developed injury models similar to those used in zebrafish and mice—ventricular resection and cryoinjury—and tested them in a non‐traditional animal model, the American alligator.Hatchling alligators were injured or sham operated, and allowed to recover over periods of time up to 4 months. Preliminary data from hatchlings 1, 3, and 14 days post‐injury show appearance of regenerative cardiomyocytes around the injury area. Whether this is a significant increase over background proliferation of sham operated hearts, as well as the ability to replace scar tissue with cardiomyocytes, remains to be determined. Results from this study will demonstrate whether the alligator— with its four‐chambered heart, and independent systemic and pulmonary pressure generation—can be a useful model in studies of cardiac regeneration, and serve to further elucidate the phylogenetic and evolutionary relationship between the aforementioned clades with regard to regenerative capacity.Grant Funding Source: Supported by California Institute for Regenerative Medicine
The effects of developmental nicotine exposure on hypoglossal motoneuron morphology and electrophysiology (871.2)
Authors: Powell Gregory , Levine Richard , Fregosi Ralph 
Published: June 2021

Developmental nicotine exposure (DNE) is known to have significant effects on motoneuron electrophysiology and morphology. Previous work in hypoglossal motoneurons (XIIMN) of neonatal rats exposed to nicotine in utero has shown decreased excitatory synaptic input, desensitized nicotinic acetylcholine receptors, increased input resistance, a left‐shifted frequency‐current curve as well as increased gain, and preliminary evidence for a decreased soma size. To further examine the effects that DNE has on XIIMNs, we have used whole‐cell patch clamp techniques to record responses to injected sine‐wave currents while neurobiotin passively fills the neurons. Filled cells were visualized using a DAB reaction followed by a detailed morphological reconstruction using the Neurolucida system. Response to sinusoidal current injection was used to record spike firing resonance, which is indicative of spike‐timing precision and variability. These measurements are useful for examining potential changes of the input‐output efficiency of XIIMNs by DNE. Preliminary data indicate significantly increased size of dendritic surface area in DNE cells (n=8 control; 2 DNE). Nicotine exposed cells also appear to be less responsive to sine wave inputs, and more variable in their response as well (n=4 control; 7 DNE).Grant Funding Source: Supported by NIH R01HD071302, AHA 12GRXIT120S0345
Calorie restriction as a new approach for resetting carotid body chemoreflex control in heart failure (873.11)
Authors: Del Rio Rodrigo , Marcus Noah , Schultz Harold 
Published: June 2021

The carotid body (CB) plays a pivotal role in the increased chemosensitivity following chronic heart failure (CHF). The mechanisms underlying the CB potentiation in CHF are not fully understood. However, it is known that oxidative stress contributes to the exaggerated CB function. Since calorie restriction (CR) has been shown to reduce oxidative stress we hypothesized that CR normalizes CB afferent activity and restores normal chemoreflex drive in CHF. Male rats (200g) were subjected to coronary artery ligation or sham surgery. CHF and sham animals were randomly allocated into 2 groups: Ad libitum calorie intake (AL) or CR (30% less caloric intake compared to AL). Ventilatory chemoreflex responses to hypoxia (FiO2~10%) were measured 4 weeks after AL or CR. CB chemoreceptor afferent neural activity was recorded and Mn‐superoxide dismutase (SOD2) protein expression was assessed in CB chemoreceptor cells. CHF‐AL rats compared to sham‐AL rats displayed exaggerated ventilatory chemoreflex response to hypoxia, potentiation of CB afferent discharge, and reduced SOD2 expression in CB chemoreceptor cells (21±1 vs. 73±3 a.u., CHF‐AL vs. sham‐AL, p<.05). CR reduced ventilatory chemoreflex function in CHF rats to levels comparable to the ones obtained in sham‐AL rats. CR in sham rats had no effect on chemoreflex function. Compared to CHF‐AL rats, CHF‐CR rats displayed reduced CB afferent discharge during hypoxia (150±13 vs. 262±21 Hz, CHF‐CR vs. CHF‐AL, p<.05) and a 3‐fold increase in SOD2 protein expression in CB chemoreceptor cells. Our results show that CR increases SOD2 expression in CB chemoreceptor cells, prevents abnormal CB afferent function, and normalizes chemoreflex control in CHF rats.Grant Funding Source: Supported by NIH PO1‐HL62222
Unilateral renal denervation decreases adrenergic and angiotension II type I receptors in the PVN of rabbits with chronic heart failure (875.15)
Authors: Schiller Alicia , Haack Karla , Zucker Irving 
Published: June 2021

Hallmarks of chronic heart failure (CHF) are increased sympathetic tone and blunted baroreflex sensitivity. Renal denervation (DNx) improves these symptoms in hypertensive patients and in experimental models of CHF. However, the mechanism(s) underlying the protective effects of renal DNx are unknown. The paraventricular nucleus (PVN) is a cardiovascular control region of the brain known to influence all sympathetic nerve beds. Both α‐ and β‐adrenergic (α1cAR, β1AR) and angiotensin II type 1 (AT1) receptors in the PVN contribute to baroreflex sensitivity. Changes in α1cAR, β1AR and AT1 expression in the PVN following renal DNx are unclear. We hypothesized that renal DNx would attenuate the adrenergic and AT1 alterations in the PVN in CHF. 13 New Zealand White rabbits either underwent DNx (stripping the left renal artery of all visible fibers) / sham(INV) surgery. Four weeks post‐surgery, animals were then either not paced (Sham‐INV), or paced at 380 BPM to induce CHF (CHF‐INV or CHF‐DNx), which was confirmed by echocardiography. Western blot analyses of PVN micropunch lysates indicated that CHF‐INV rabbits had a significant increase in β1AR compared to Sham‐INV (0.17 ± 0.01 vs 0.11 ± 0.02, p < .05) and this was attenuated in CHF‐DNx rabbits (0.09 ± 0.001, p < .05). Compared to CHF‐INV rabbits, CHF‐DNx rabbits showed a decrease in both α1cAR (0.56 ± 0.17 vs 0.23 ± 0.01) and AT1 (0.38 ± 0.09 vs 0.15 ± 0.03) protein. These results suggest that withdrawal of the renal nerves by DNx decreases receptors within the PVN that impact sympathetic outflow in CHF.Grant Funding Source: Supported by AHA PREDOC14700045 and PO1HL62222
The effects of ketamine on the immune response in the fetal ovine brain in response to hypoxic hypoxia (877.8)
Authors: Thomas Brandi , Chang Eileen , Miguel Zarate , Arndt Thomas , Wood Charles 
Published: June 2021

Fetal hypoxia is a reduction in oxygen supply to the fetus. HH occurs when maternal and fetal partial pressure of oxygen is decreased due to maternal partial ventilatory restriction. Recently, our lab reported that HH increased inflammatory genes in the fetal brain, and KET reduced the expression by microarray analysis. We hypothesized that HH causes an inflammatory reaction in the fetal ovine brain, and KET attenuates this response. We examined fetal ovine brain (n=3‐5/group) where mother and baby were chronically catheterized, and tracheostomy was performed on the ewe. A 50 % decrease in partial pressure of oxygen was induced by administering nitrogen gas directly to the ewe for 30 min. KET was administered intravenously to the fetus 10 min prior to the induction of HH. Brains were collected 24 hrs post HH stimulus, fixated in 4% paraformaldehyde, and then embedded in paraffin blocks for hematoxylin and eosin staining. After tissue examination under light microscope, lymphocytic infiltration, congestion in blood vessels, and the presence of proteinaceous substances were evaluated by a 5‐point scoring criteria in the HH brains. KET produced a decrease in inflammatory response in tissues subjected to HH, and the induction of HH produced a higher inflammatory response when compared to normoxia group (P<0.05, Friedman test). We conclude that KET decreases the level of inflammation in the fetal ovine brain exposed to HH.Grant Funding Source: Supported by NIH grants HD033053 and HD05761 and by the APS STRIDE program.
Plasticity of adenosine and endothelin I tone on cardiovascular function in embryonic chickens (Gallus domesticus): effects of developmental hypoxia (879.5)
Authors: Crossley Dane , Iversen Nina , Baatrup Erik , Wang Tobias 
Published: June 2021

Chronic hypoxic incubation of embryonic chickens is a common environmental challenge used to assess plasticity in the development of cardiovascular function in vertebrates. Hypoxic stress increases vascular growth, circulating catecholamines, and cholinergic tone while decreasing resting arterial pressure, adrenergic tone, and sensitivity to exogenous nitric oxide in some chicken breeds. Given the limited contribution of the central nervous system to cardiovascular homeostasis throughout the majority of chicken development hypoxia may also alter regulatory elements if they exhibit plasticity. We investigated the plasticity of key local regulatory ligands, adenosine and endothelin I in embryonic chickens induced by hypoxia (15%O2). At day 15 (70%) and 19 (90%) of a 21 day incubation period embryos from normoxic and hypoxic conditions were instrumented to measure arterial pressure and heart rate. Adenosine produced a dose dependent hypotensive bradycardia that increased in intensity with age. Endothelin I produced a pronounced hypertension at the maximal dose on day 15 and a dose dependent hypertension at day 19. Chronic hypoxic incubation blunted the adenosine response while it intensified the pressure response to endothelin I. Finally, the embryonic cardiovascular response adenosine receptor blockade with theophylline on day 19, a sustained hypertension, was absent in embryos incubated in 15% O2. These findings indicate embryonic chickens utilize adenosine and endothelin I to maintain cardiovascular homeostasis. Further both responses exhibit regulatory factor specific plasticity.Grant Funding Source: Supported by NSF CAREER IBN IOS‐0845741 to DAC
Effect of posture on heart rate control prior to and following dynamic leg exercise (881.8)
Authors: White Daniel , Kay Victoria , Moralez Gilbert , Benson Tyler , Carlton Joshua , Eubank Wendy , Raven Peter 
Published: June 2021

Reflex control of cardiovascular function is paramount in maintaining homeostasis both before and after exercise. We investigated the influence of posture on arterial baroreflex function both before and after prolonged moderate to high intensity exercise.9 healthy subjects (1 female) aged 24.4 years (±1.16) volunteered for protocol 1 of the study and 13 healthy subjects (3 female) aged 25.5 years (±0.88) volunteered for protocol 2. Each subject underwent graded exercise test either upright (UR) (protocol 1) or semi‐recumbent (SR) (protocol 2). During both protocols 1 and 2 neck pressure/neck suction protocols were performed at rest, exercising HRs of 120 and 150 bpm, and recovery. Reflex data for HR and MAP were analyzed and baroreflex curves were calculated. Repeated measure ANOVAs was performed and Neuman‐Keuls post hoc analysis was used when differences were detected. Significance was set at P<0.05.Significant differences were identified in operating point values of HR between SR and UR at rest (P<0.001), and between rest and recovery in both SR and UR (p<0.001). Differences were also identified in Carotid‐cardiac baroreflex response range and maximum gain between and within all conditions (p<0.05).Differences in the neural reflexive control of HR at rest and during recovery are related to postural changes in cardiopulmonary loading.Grant Funding Source: Supported by TACSM SRDA
Breathing heliox reduces expiratory flow limitation and improves exercise performance in adult survivors of extreme preterm birth (882.4)
Authors: Duke Joseph , Mangum Tyler , Elliott Jonathan , Gladstone Igor , Lovering Andrew 
Published: June 2021

Extreme preterm birth (<32 weeks gestational age) results in arrested development of the lung characterized by abnormal alveologenesis and pulmonary vasculogenesis causing obstructive lung disease that persists into adulthood. We have recently shown that adults with a history of extreme preterm birth (PRE) have reduced aerobic exercise capacity relative to full term controls (CONT) that is not explained by pulmonary gas exchange inefficiency during exercise. These PRE subjects also have significant exercise‐induced flow limitation (EIFL), which has been suggested to be associated with a reduction in exercise capacity in healthy humans and in COPD subjects. Therefore, we hypothesized that reducing EIFL by breathing heliox (21% O2, 79% He) would improve exercise performance. Both PRE (n = 4) and CONT (n = 4) subjects performed two cycle ergometer exercise tests to exhaustion at 80% of their maximum power output; one breathing room air and one breathing heliox. Measurements breathing heliox were compared to those breathing room air at iso‐time. Flow‐volume loops were measured at rest and during both exercise tests to quantify EIFL. EIFL significantly decreased in PRE from room air (57% of tidal volume; VT) to heliox (9% VT), while CONT did not exhibit EIFL in either condition. Time to exhaustion significantly increased in PRE (38%), but not CONT (9%), breathing heliox compared to room air. These data suggest that excessive EIFL, may lead to an excessive work of breathing and/or mechanical constraints to increasing tidal volume during exercise, thereby significantly limiting exercise performance in PRE subjects.Grant Funding Source: Supported by AHA Scientist Development Grant and OHSU Early Clinical Investigator Grant
Heat balance in SHR is impaired during exercise until fatigue in warm environment (884.1)
Authors: da Cunha Daise , Campos Helton , Leite Laura , Drummond Lucas , Coimbra Cândido , Natali Antônio , Prímola‐Gomes Thales 
Published: June 2021

Heat balance in SHR is impaired during exercise until fatigue in warm environment Daise N.Q. Cunha1, Helton O. Campos1, 3, Laura H.R. Leite2, Lucas R. Drummond1, Cândido C. Coimbra3, Antônio J. Natali1, Thales N. Prímola‐Gomes1. Department of Physical Education, UFV, Viçosa, Brazil1. Department of Physiology, UFJF, Juiz de Fora, Brazil2. Department of Phvsiology and Biophysics, UFMG, Belo Horizonte, Brazil3.To investigate thermal balance in SHR subjected to submaximal exercise until fatigue (SMEF) in warm environment. Male SHR and Wistar rats (WIS) were submitted to SMEF at 60% VO2max and 5º inclination in thermoneutral (25°C, TE) and warm (32°C, WE) environments. Body (Tb) and tail skin (Ttail) temperatures, and oxygen consumption (VO2), were registered during exercise. Total time of exercise (TTE), workload (W), mechanical efficiency (ME) and heat storage (HS) were determined. SHR‐WE showed higher heat production in comparison to WIS‐WE (from 15‐17 min). Baseline Ttail was greater in WE, but demonstrated an equal increase among SHR and WIS in both environments. Animals exercising in the WE had higher Tb in comparison to TE (from 4‐17 min), while SHR‐WE showed higher Tb in comparison to SHR‐TE after 8 min of exercise. SHR had lower ME compared to WIS in TE and WE. Moreover, SHR‐WE showed higher HS compared to SHR‐TE. In conclusion SHR exhibited an increase in heat production and heat storage during exercise until fatigue in warm environment resulting in aggravated hyperthermia linked to lower mechanical efficiency. We used FASEB Statement of Principles for the use of animals in research.Grant Funding Source: CAPES
A single bout of moderate intensity resistance exercise improves neural mechanisms of arterial pressure control in L‐NAME hypertensive rats (884.14)
Authors: Barreto André , Mota Marcelo , da Silva Tharciano , Fontes Milene , Santana‐Filho Valter , Santos Márcio 
Published: June 2021

Resistance training has been used as non‐pharmacological approach for control hypertension. A single bout of exercise can lead to a post exercise decreased blood pressure especially in hypertensive individuals. However neural central mechanisms involved in this modality of exercise remain unclear. Therefore the aim of this study was to evaluate the acute effects of a single bout of resistance exercise (RE) on blood pressure, baroreflex sensitivity (BRS) and cardiac autonomic balance in L‐NAME hypertensive rats. The resistance exercise (RE) consisted of 10 sets of 10 repetitions with 1 minute of interval between sets performed at 60% of one repetition maximum test, in squat‐training apparatus. Mean arterial pressure (MAP) was measured by a catheter placed in the carotid artery and recorded 15 before (baseline) and during 120 minutes post exercise. BRS was analyzed by sequence method and cardiac autonomic balance by heart rate variability in the frequency domain. Hypertension decreased BRS (from 2.03 ± 0.3 to 1.05 ± 0.2 mmHg/s, p<0.05) and increased both LF/HF ratio (from 0.12 ± 0.03 to 0.34 ± 0.05 nu, p<0.01) and LFsys (from 2.69 ± 0.1 to 5.19 ± 0.5 mmHg2, p<0.05) in baseline time. A single bout of moderate RE reduced MAP between 45’ to 120’ (p<0.001) and heart rate (HR) from 75’ to 120’ (p<0.05). Furthermore increased BRS from 15’ to 105’ (p<0.01) and both LF/HF ratio (p<0.05) and LFsys (p<0.001) were reduced. These results suggest that a single bout of moderate RE promotes a better hypertension control by improved BRS and cardiac autonomic balance in L‐NAME hypertensive rats.Grant Funding Source: Supported by FAPITEC/SE
Metabolic profile and inflammatory markers in an endurance trained and untrained population (884.20)
Authors: Vera Desiree , Castillo Micaela , Oliver Kari , Rosario Emily , Granquist Megan , Dunn Sarah 
Published: June 2021

Obesity is reaching epidemic proportions worldwide. Studies have now shown that obesity is the result of an imbalance in metabolic factors that have been triggered by a physiological stress resulting in an inflammatory state. Physical activity may positively impact metabolic dysfunction (insulin, glucose) and inflammatory markers, C‐reactive protein (CRP) and Interluekin‐6 (IL‐6), in adults, ultimately influencing one's risk for disease. With training, IL‐6 has been shown to elicit a pro‐ or anti‐inflammatory like state within the muscle; therefore it is a multi‐factorial cytokine. Whether there is a significant difference between endurance trained and untrained male and female adults in association to metabolic profile and inflammation markers is unknown. Therefore, the purpose was to examine the differences between body composition and metabolic profile (insulin, CRP, IL‐6, etc.) in trained (n=15, age 26.9 ± 14.4 yr) and untrained (n=19, age 36.7 ± 19.2 yr) adults. Fasting venous whole blood (40 ml) and body composition measurements (percent body fat, fat mass, etc.) were obtained from apparently healthy individuals. Enzyme‐linked immunosorbent assays were conducted to analyze fasting blood plasma concentrations of insulin, CRP, and IL‐6. An Independent T‐test was used to identify significant differences (p < 0.05) between trained and untrained (N=35). Significant differences exist in body composition (p < 0.05) and CRP (p < .001). Although fasting plasma insulin and IL‐6 were elevated in the untrained group, no significant differences were found. In conclusion, a significant difference exists between trained and untrained individuals for body composition and CRP suggesting that physical activity may decrease one’s risk of developing disease. Despite a significant difference with CRP in the trained versus untrained individuals, IL‐6 may elicit an anti‐inflammatory like property with endurance training ultimately protecting the trained individuals.Grant Funding Source: Supported by STEM