bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Carotid Body‐mediated Chemoreflex Drive in Heart Failure: a Matter of Flow
Authors: Andrade David C , Schultz Harold D , Marcus Noah J , Toledo Camilo , Lucero Claudia , Del Rio Rodrigo 
Published: November 2023

Enhanced carotid body (CB) chemoreflex function in heart failure (HF) is strongly related to cardiorespiratory disorders and the progression of the disease. Importantly, HF patients with an increased CB chemoreflex drive exhibit a poor prognosis. The mechanisms underlying CB sensitization during HF are not fully understood. We hypothesized that blood flow restrictions to the CB region during the progression of HF severely impact CB chemoreflex function. We sought to determine whether blood flow reductions to the CB in the setting of HF induced chemoreflex potentiation. Myocardial infarcted Sprague‐Dawley rats were used as a low output HF model (LowHF) and aortocaval fistulated rats were used as a high output HF model (HighHF). All experiments were performed 8 weeks after HF induction. Blood flow to the CB region was estimated by carotid artery Doppler imaging. Autonomic function was measured by heart rate variability (HRV) and atropine‐propranolol test. The ventilatory CB‐mediated chemoreflex drive was measured by plethysmography allowing the rats to breathe hypoxic gas (FiO2 10%). Resting breathing recordings were visually inspected to scored apneas and hypopneas (AHI). Expression of the flow sensitive transcription factor, Krupper‐like factor‐2 (KLF2) was assessed by immunofluorescence and immunoblot. LowHF rats and HighHF rats displayed similar degrees of autonomic imbalance (P>.05, HRV and HR response to atropine/propranolol). LowHF rats exhibited a significantly enhanced CB‐mediated hypoxic ventilatory response compared to sham rats (222±20 vs. 112±6 ml/min/100g, LowHF vs. sham, respectively; P<.05) and compared to HighHF rats (222±20 vs. 55±7 ml/min/100g, LowHF vs. HighHF, respectively; P<.05). However, AHI was increased (P<.05) in both LowHF and HighHF rats compared to sham rats (9±1 vs. 16±2 vs. 20±2 events/h, sham vs. LowHF vs. HighHF, respectively). Carotid artery blood flow was decreased in LowHF (P<.05) compared to sham rats and HighHF rats (17±1 vs. 28±4 vs. 35±2 ml/min LowHF vs. sham vs. HighHF, respectively). KLF2 expression in the CB was markedly reduced in LowHF compared to sham rats while no changes in KLF2 expression was found in HighHF. Our results showed that carotid blood flow reductions during the progression of low output HF reduced CB KLF2 expression and enhanced the CB chemoreflex drive. CB chemoreflex sensitivity was not altered in high output HF in which carotid blood flow and KLF2 remained normal.Support or Funding InformationSupported by FONDECYT 1140275 and NIH PO1‐HL62222.
Effect of Six Months of Cardiac Rehabilitation on Autonomic Function in Coronary Artery Disease Patients
Authors: Badrov Mark B , Norton Katelyn N , Lalande Sophie , Suskin Neville , Shoemaker J Kevin 
Published: November 2023

We investigated the effects of a 6‐month exercise training‐based cardiac rehabilitation (CR) program on autonomic function in patients with coronary artery disease (CAD). Twenty‐two CAD patients (4 women; 62 ± 8 yrs, 172 ± 9 cm, 86 ± 13 kg) were studied prior‐to and following six months of aerobic and resistance training‐based CR. Seventeen healthy aged‐matched controls were also studied (6 women; 60 ± 9 yrs, 169 ± 8 cm, 73 ± 14 kg). We evaluated resting blood pressure (BP; manual sphygmomanometry), muscle sympathetic nerve activity (MSNA; microneurography; CAD, n = 14), heart rate variability (HRV; time‐ and frequency‐domain), and cardiovagal baroreflex sensitivity (BRS; sequence method). At baseline, prior to CR, CAD patients had greater burst frequency (48 ± 8 vs. 36 ± 8 bursts/min; P < 0.01) and burst incidence (81 ± 7 vs. 62 ± 10 bursts/100 heart beats; P < 0.01) in comparison to healthy controls. No differences at baseline between CAD patients and healthy controls were found for resting BP, any index of HRV, or cardiovagal BRS (all P > 0.05). Six months of exercise‐based CR lowered resting mean arterial BP (86 ± 10 to 83 ± 7 mmHg; P < 0.05) and systolic BP (122 ± 16 to 116 ± 11 mmHg; P < 0.05) in CAD patients. In CAD patients, CR reduced burst frequency (48 ± 8 to 39 ± 11 bursts/min; P < 0.01; d = 0.95) and burst incidence (81 ± 7 to 66 ± 17 bursts/100 heart beats; P < 0.01; d = 1.32). Also, following CR, and in contrast to pre‐CR, levels of MSNA were not significantly different between CAD and healthy controls for burst frequency (P = 0.43) and burst incidence (P = 0.39). No index of HRV (all P > 0.05) or cardiovagal BRS (P = 0.78) was changed in CAD patients following CR. In conclusion, six months of exercise training‐based CR reduced baseline BP and sympathetic outflow in CAD patients to levels observed in healthy controls.Support or Funding InformationCanadian Institutes for Health Research (CIHR) Team Grant “Physical Activity, Mobility, and Neural Health” (Grant #217532).
Hypertension Impairs Peripheral and Cerebrovascular Reactivity to Isocapnic Hypoxia in Humans
Authors: Fernandes Igor Alexandre , Campos Monique Opuszcka , Mansur Daniel Elias , Mattos João Dario , Rocha Marcos Paulo , Nóbrega Antonio Claudio Lucas 
Published: November 2023

Hypertensive animal models indicate impairment in both peripheral and cerebrovascular reactivity to isocapnic hypoxia. However, it is still uncertain whether these findings could be translated to a setting of human hypertension. Therefore, the main purpose of this investigation was to determine the impact of hypertension on peripheral and cerebrovascular reactivity to isocapnic hypoxia in humans. Six normotensive (NT, 44 ± 11yrs, mean arterial pressure (MAP) 87 ± 6 mmHg) and 5 hypertensive men (HT, 46 ± 11yrs, MAP 110 ± 9 mmHg) were exposed to 5‐min bouts of: (1) Normoxia (21% O2) and (2) isocapnic‐Hypoxia (10%O2). Oxygen saturation (pulse oxymetry), beat‐to‐beat MAP (photoplethysmography), muscle sympathetic nerve activity (MSNA [microneugraphy]) and partial pressure of end‐tidal carbon dioxide (PETCO2) were monitored throughout the study. Clamping of PETCO2 was also performed through a rebreathing system and blood flow in the femoral (FA), internal carotid (ICA) and vertebral arteries (VA) was simultaneously quantified via Doppler ultrasound at the last 30s of each condition. Both experimental groups showed similar reductions in oxygen saturation as a result of isocapnic‐hypoxia exposure (NT −25.7 ± 3.3 vs. HT −21.2 ± 4.0%, p > 0.05). No substantial changes on MAP and PETCO2 were observed during isocapnic hypoxia. While comparable increases in ICA perfusion were observed (NT +204.4 ± 32.7 vs. HT +134.8 ± 65.5 ml.min−1, p > 0.05), only NT exhibited a significant increment in VA blood flow (+78.1 ± 24.5 vs. HT +8.3 ± 7.9 ml.min−1, p < 0.05). At the peripheral circulation, HT presented a drastic drop in FA blood flow (−110.2±43.0 ml.min−1) while NT showed a significant increase in the FA perfusion (+73.9 ± 37.4 ml.min−1, p < 0.05). MSNA recordings revealed greater increases in sympathetic activation of hypertensive individuals (HT +12.7 ± 6.7 vs. NT +3.6 ± 1.6 bursts/min, p < 0.05). In conclusion, hypertension impairs both peripheral and cerebrovascular reactivity to isocapnic hypoxia and MSNA recordings may suggest a contribution of a sympathetic overdrive to this response.Support or Funding InformationGrant Funding Source: CNPq, FAPERJ, CAPES e FINEP
Effects of Acute Hypoxia on Human Adipose Tissue Lipoprotein Lipase Activity and Lipolysis
Authors: Mahat Bimit , Chassé Étienne , Mauger Jean‐François , Imbeault Pascal 
Published: November 2023

ContextAdipose tissue regulates postprandial lipid metabolism by storing dietary fat through lipoprotein lipase (LPL)‐mediated hydrolysis of dietary triglycerides, and by inhibiting non‐esterified fatty acid (NEFA) delivery to nonadipose tissues. Studies conducted in animal showed that acute intermittent hypoxia, a model of obstructive sleep apnea, reduce adipose tissue LPL activity and increase NEFA release, adversely affecting postprandial lipemia. These observations remain to be tested in humans.ObjectiveTo investigate the effects of acute hypoxia on human adipose tissue LPL activity and lipolysis.MethodsDifferentiated human preadipocytes were exposed to hypoxia (3% O2) for 24h and adipose tissue biopsies were obtained from 10 healthy men exposed for 6 hours to either normoxia or intermittent hypoxia following an isocaloric high‐fat meal.ResultsIn differentiated human preadipocytes, acute hypoxia induced a 6‐fold reduction in LPL activity (p<0.001). In humans, the rise in postprandial triglyceride levels did not differ between normoxia and intermittent hypoxia. NEFA levels were significantly higher during intermittent hypoxia session (condition effect, p<0.05). Intermittent hypoxia did not affect subcutaneous abdominal adipose tissue LPL activity. No difference in lipolytic‐induced responses of isolated subcutaneous abdominal adipocytes were observed between normoxia and intermittent hypoxia sessions.ConclusionsAcute hypoxia strongly inhibits LPL activity in differentiated subcutaneous abdominal preadipocytes. Acute intermittent hypoxia increases circulating plasma NEFA in young healthy men, but does not seem to affect postprandial triglyceride levels, nor subcutaneous abdominal adipose tissue LPL activity and adipocyte lipolysis.Support or Funding InformationThe study is dedicated to the memory of our colleague Michaël Babinsky. We are grateful to Mrs. Ann Beninato and Sabrina Ait‐Ouali for their technical assistance. Bimit Mahat is a recipient of a Ontario Graduate scholarship. Étienne Chassé is a recipient of a Institut de recherche de l'Hôpital Montfort scholarship. This study was supported by the Natural Sciences and Engineering Research Council of Canada as well as the University of Ottawa.
Beneficial Effects of Physical Training on the Vascular Dysfunction Induced by Intermittent Hypoxia during Apnea
Authors: ESTEVE Eric Jean‐Claude , El Dirani Zeinab , Lemarie Emeline , Daher Ahmad , Joumaa Wissam , Faury Gilles 
Published: November 2023

Obstructive sleep apnea syndrome (OSA) is characterized by multiple breathing interruptions during sleep due to transient closing of the superior airways. This induces chronic intermittent hypoxia (IH), which enhances cardiovascular dysfunction and remodeling, potentially leading to hypertension and cardiac infarct. Since physical training has previously been described as limiting the extent and occurrence of several cardiovascular diseases, the aim of this study was to evaluate the beneficial effect of intensive training on the reactivity of arteries and calcium signaling in vascular smooth muscle cells (SMC) of rats submitted to IH.Four groups of Wistar rats were randomly assigned: N (normoxic sedentary rats), NIE (normoxic intensively exercised rats), IH (intermittent hypoxic sedentary rats) and IHIE (intermittent hypoxic intensively exercised rats). IH consisted in alternating normoxia (21%O2) and hypoxia (5%O2) every 30 sec in the cages for 8 h/day during 3 weeks. Exercise sessions were conducted 5 times/week in NIE and IHIE rats as a double fast 24 min walk with a speed progressively rising from 16 to 30 m/min. After 21 days of normoxia or IH (with/without training), the aortic ring tone in response to increasing doses of vasoactive agonists has been investigated by tension arteriography. Also, calcium imaging of cultured aortic SMC and protein expression of calcium channels were performed to examine the effects of lack of oxygen and/or training at the cellular and molecular levels respectively.21 days of exposure to IH had no impact on the aortic response to tested vasoconstrictors (10−11 to 10−4 M endothelin‐1 and 10−12 to 10−5 M phenylephrine). IH also reduced by up to 20% the vasorelaxant effect of acetylcholine (at 10−6 M), which is in accordance with the previously shown endothelial dysfunction generated by IH. On the contrary, intensive training increased by ~20% the vasodilatory effect of acetylcholine (10−10 to 10−3 M), compared to aortic responses of sedentary animals, while it decreased by ~50% the aortic response to the vasoconstrictors endothelin‐1 and phenylephrine in both normoxic and IH groups. Intensive training also increased the caffeine‐induced elevation of cytoplasmic calcium level in aortic SMC. At the molecular level, the protein expressions of major calcium channels like RyR or TRP were altered during hypoxia and/or exercise modulating SMC calcium signaling. Our results suggest that intensive exercise training could decrease the adverse effects of IH on the cardiovascular physiology trough calcium homeostasis. This could lead to improvements in the treatment of OSA patients.Support or Funding InformationUGA, INSERM, Agir@Dom, AUF (PCSI)
Effect of Electrical Stimulation on Grasshopper Jumping Muscle
Authors: Yazdani Ariella A. , Broadwell Randi C. , Kirkton Scott D. 
Published: November 2023

Skeletal muscles can undergo biochemical and physiological changes due to exercise training. For example, aerobic exercise training may lead to an increased mitochondria volume, a higher proportion of slow twitch myosin ATPase, and a reduced rate of lactic acid production. Similar changes in mammalian muscle have also been demonstrated using electrical stimulation. However, it is unclear if invertebrate muscle also responds to training or electrical stimulation. We examine whether Schistocerca americana grasshopper jumping muscles are affected by electrical stimulation. Grasshopper jumping muscle is one of the few invertebrate muscles to produce lactic acid during locomotion. Electrical probe leads are placed near the coxa on the ventral side of the animal. The muscle was stimulated with a single pulse width of 2 ms at 0.075 V and repeated at a frequency of 100 Hz. We electrically stimulate the entire jumping muscle, including both the flexor and the extensor, to elicit continuous muscle contractions in a single metathoracic leg. To invoke a training response, a grasshopper is stimulated for 5 hours daily for 5 consecutive days. The lactate production rate of trained and untrained grasshopper muscle will then be fluorometrically measured after 5 min, 30 min, 60 min, 180 min, or 300 min of electrical stimulation. We predict that repeated stimulation would alter the rate of lactic acid production. Since grasshopper jumping muscle is similar to human muscle, this research may provide insight into fundamental questions about muscle plasticity.Support or Funding InformationUnion College Undergraduate Research Committee
Age‐Related Decline of Anoxia Tolerance in Adult Drosophila melanogaster
Authors: Sargent James C. , Campbell Jacob B. , Harrison Jon F. 
Published: November 2023

Cell death occurring from anoxia is considered to be the cause of many human diseases such as heart attack and stroke. Though much is known about the cause of anoxia in such conditions, we still have a poor understanding of the mechanisms causing cell death and the genetic and physiological processes responsible for variation in survival of anoxia. Drosophila melanogaster are particularly interesting models for studying responses to anoxia as they can survive many hours of anoxia and most of their metabolic pathways are similar to those of humans. We hypothesized, based on studies with humans, that younger adults would have a higher anoxia tolerance than older adults. We exposed adult Drosophila, ages 1, 3, 5, 7, 9, and 12 days old, to six hours of anoxia. Survival was assessed 24 hours post‐treatment; surviving individuals exhibited movement if stimulated. Survival declined with age in a linear fashion for females and in a more exponential fashion for males. Seventy nine percent of adults one day past eclosion survived six hours of anoxia; while only 10% of twelve‐day‐old adults survived. Additionally, we measured ATP in 1 and 12 day old Drosophila indifferent durations of anoxia. In anoxia, ATP levels declined rapidly to near‐zero levels in both 1 and 12 day old adults; thus the better capacities of young adults to survive anoxia are not due to a better capacity to keep ATPelevated. This age‐related decline in anoxia tolerance may be due to loss of capacities to prevent or repair anoxia‐related damage. Overall, these data show that patterns of gender‐ and age‐associated variation in tolerance to anoxiaare similar in Drosophila and mammals, suggesting that Drosophila may be underutilized models for studies of the genetic and biochemical mechanisms of pathology of stroke and heart disease.Support or Funding InformationThis research was partially supported by NSF IOS 1256745 and the School of Life Sciences Undergraduate Research (SOLUR) Program at Arizona State University, Tempe Campus.
Using confocal imaging to understand the effect of atmospheric oxygen on insect respiratory systems
Authors: Gstrein Gregory , Arthur Kathryn , Parker Greg , Friedman Jessica , Brooks John Vanden 
Published: November 2023

Recent geochemical models suggest that over geologic time atmospheric oxygen has varied from as low as 12kPa and as high as 31kPa. These changes in atmospheric oxygen would have had strong effects on the physiology and evolution of organisms living at those times including insects and other arthropods. Insects transport oxygen completely in the gas phase through hollow tubes known as tracheae. We have hypothesized that this unique respiratory system of insects made them more susceptible to changes in atmospheric oxygen. Previously, it has been shown that as insects increase in body size, their tracheal system increases at a faster rate and may eventually limit the maximum body size of insect species. As a corollary, we have shown that rearing oxygen is inversely correlated with tracheal system density in some insects; with hyperoxia decreasing tracheal investment and hypoxia increasing tracheal investment. Therefore, a hyperoxic rearing environment may remove the spatial constraint of the tracheal system and allow insects to achieve larger body sizes. However, a limit to these studies has been a focus on the large conducting tracheae which drive bulk flow of gases through the system. Previous research has largely ignored the final oxygen delivery component of the tracheal systems.Here we look at the effect of rearing oxygen on the smallest components of the tracheal system – the blind ended tracheoles across which the actual oxygen delivery to the tissues occurs. To this end, we have developed a new confocal imaging technique to image and analyze insect tracheoles in 3D, which allows for increased resolution and spatial imaging capability. The density of tracheoles, tracheolar diameters, and network properties of the tracheolar branching all affect oxygen delivery and may be a major driver in the control of insect body size. To understand these effects, we reared Drosophila melanogaster under three different oxygen partial pressures (12kPa ‐ hypoxia, 21kPa ‐ normoxia, and 31kPa hyperoxia) that match the range of variation seen over geologic time. We then carried out confocal imaging of the tracheolar network in the flight muscle dissected out of the thorax of these D. melanogaster. The tracheolar network auto‐fluoresces under the confocal microscope excitation allowing us to obtain high resolution 3D reconstructions of the respiratory system. By using ImageJ and AVIZO, we were able to measure tracheal and tracheolar diameters and characterize the network branching patterns of these D. melanogaster reared under the varying oxygen levels. By measuring these two components of the insect respiratory system, we have shown that oxygen does effect tracheolar diameters and has a strong effect on branching pattern and tracheolar investment in the flight muscle of D. melanogaster.Support or Funding InformationMidwestern University College of Veterinary Medicine Fellowship Program
Metabolic and Genetic Implications of Survival in Anoxic Drosophila
Authors: Campbell Jacob B , Harrison Jon F 
Published: November 2023

Anoxia or severe hypoxia is a fundamental component of pathologies associated with heart disease, stroke and many other human pathologies; yet we still lack a fundamental understanding of how anoxia/severe hypoxia kills and the mechanisms responsible for the wide variation in anoxia tolerance across animals. Drosophila larvae feed on the yeasts of rotting fruits in a semi liquid environment, and as a consequence, the larvae regularly experience episodes of hypoxia/anoxia whereas adults live in air and are likely to experience hypoxia on rare occasions. Perhaps surprisingly, larvae are much less tolerant of anoxia than adults; nearly 100% of adults survive up to 4 hours of anoxia while less than 50% of third in star larvae survive anoxic bouts greater than 90 minutes. We used biochemical and physiological methods to assess stage‐related variation in the ability to match ATP supply and demand, and in addition, we conducted a genome‐wide association study to find and then verify candidate genes responsible for variation in anoxia survival within populations of larvae and adults. Anoxia induced strong decreases in glycogen levels in both larvae and adults; however, both stages also showed strong increases in free glucose indicating that carbohydrate depletion is likely not a cause of death. Both larvae and adults accumulated lactate, but larvae did so at a higher rate during the first hour of anoxic exposure which suggests that high locomotion of larvae during initial exposure to hypoxia requires high rates of anaerobic metabolism that may be functionally linked to mortality. Preliminary measures of ATP show that ATP declines to near zero at the first measured time points—2 hours for adults and 30 minutes for larvae. Survival of a 1 hour anoxia exposure was highly repeatable but varied greatly across 178 lines from the Drosophila Genetics Reference Panel ranging from 25–95%. Thirty‐two SNPs and 23 genes were associated with the variation in survival across lines, all with P values less than 0.00001. Gene ontology enrichment analysis implicates differential genes in classes involved in vertebrate angiogenesis, cell proliferation, membrane/cytoskeletal remodeling, and fatty acid metabolism associated with differential survival across lines. Several of the identified genes linked to survival across the DGRP lines have human orthologs that have been linked to oxygen‐mediated cancer pathways and Alzheimer's progression in humans.Support or Funding InformationThis research was supported by NSF IOS 1256745.