bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerobic Exercise Training Attenuates Differences between Black and White Adults in Left Ventricular-Vascular Coupling and Wasted Pressure Effort
Authors: Maroco Joao , Lane Abbi , Ranadive Sushant , Yan Huimin , Baynard Tracy , Fernhall Bo 
Published: May 2024

Background: Black adults have a higher risk for left-ventricular hypertrophy and heart failure, when compared to white adults. This stems, in part, from their frequent potential alterations in ventricular-vascular coupling indexed by the arterial (Ea) to ventricular elastance (Ev) ratio and heightened wasted pressure effort (Ew). Exercise training preserves ventricular-vascular coupling and attenuates Ew, but whether this applies to black adults is unknown. Purpose: We hypothesized that aerobic training would attenuate reported racial differences in both left ventricular-vascular coupling and Ew. Methods: Fifty-four young adults [blacks= 24 (14 females); whites= 30 (15 females), aged: 19-35 years] completed an 8-week aerobic training intervention (3 times/wk, 65-85% peak oxygen uptake). Pre-and post-training systolic function and ventricular-vascular coupling were assessed via echocardiography. The Ew was estimated from pulse contour analysis. Pre-and-post-training changes were examined with linear mixed models. Results: Pre-training, blacks had higher Ev (difference (d) = 0.49, 95% CI: 0.14 to 0.84 mmHg/ml, p=0.007) and Ew (d= 1130, 95% CI: 477 to 1784 dyne cm−2 s, p<0.001). After training, both groups exhibited similar reductions in Ea (d= -0.22, 95% CI: -0.32 to -0.13 mmHg/ml, p<0.001). In white, but not black adults, Ev increased (dwhite= 0.30, 95% CI: 0.04 to 0.56 mmHg/ml , p=0.027) and Ea/Ev was reduced (dwhite= -0.21, 95% CI: -0.29 to -0.12 mmHg/ml, p<0.001). Conversely, black but not white adults exhibited reductions in Ew after training (dblack= -699, 95% CI: -1209 to -189 dyne cm−2 s, p=0.008). Systolic function markers (i.e., race-independent increases in ejection fraction) supported ventricular-vascular coupling results. Controlling for cardiorespiratory fitness, and body mass index attenuated training-induced changes in Ev and Ew, while controlling for sex did no change results. Conclusions: In black adults, Ew was reduced following 8 weeks of aerobic training, while Ea was reduced in both black and white adults. Although ventricular-vascular coupling was only altered in white adults, there was no difference between white and black adults in coupling or its components following training. Despite not controlling for social determinants of health shown to partly explain biological racial disparities, our data suggests a positive effect of aerobic training on risk factors associated with the development of left ventricular hypertrophy and heart failure in black adults. This study was funded by the National Instituteof Health (NHLBI 1R01HL093249-01A1 awarded to Bo Fernhall). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Vitamin B1 supplementation ameliorates high-fat diet induced exercise fatigue and improves grip strength in male mice
Authors: Luna Crystal , Leano John , Kozlova Elena , Raut Gayatri , Martinez-Lomeli Jose , Degnan Patrick , Deol Poonamjot 
Published: May 2024

Dietary deficiencies in vitamins such as thiamine (Vitamin B1) are common even in developed countries and can have a range of deleterious health effects. This trend in Vitamin B1 deficiency coincides with increased fat consumption in the American diet, particularly of soybean oil, the most widely consumed cooking oil in the U.S. which is also present in many processed foods. Here, we hypothesize that the concurrent malnutrition caused by a soybean oil-based high fat diet (SO-HFD) and a physiological deficiency in thiamine can impact regional gene expression in the brain and behavior. To test this, C57BL/6N male mice (N=10-12 per group) were fed either a low-fat chow (OSD) or an SO-HFD, with or without supplementation with 640 mg/kg of the thiamine analog thiamine tetrahydrofurfuryl disulfide (TTFD), for 18 weeks. Mice were subjected to a series of behavioral tests designed to evaluate cognition (passive avoidance test, PAT), strength (modified grip strength test, MGS), exercise endurance (treadmill test, EE), and locomotor/habituation activity (open field test, OFT). Our results showed no difference across groups on the PAT. On the MGS test, the force generated when normalized to body weight was lesser on all test days for SO-HFD as compared to OSD (p<0.05-0.0001). The TTFD supplementation improved MGS only in the SO group (p<0.05). On EE, OSD ran significantly longer before exhaustion as compared to SO (p<0.05-0.001). For one subset of animals TTFD supplementation improved the EE score in SO but not OSD (p<0.05-0.001). During the one-hour OFT, distance traveled decreased over time for both TTFD-supplemented groups only (p<0.05-0.01), indicating improvement in habituation/learning. Transcriptomic analysis of the hypothalamus and hippocampus from these mice revealed differentially expressed genes (p<0.05) that may contribute to alterations observed in the behavioral tests. Our results indicate that TTFD supplementation ameliorates HFD-induced deficits in strength and exercise endurance. TTFD supplementation improved habituation/learning on OFT regardless of diet. The Thiamine Advocacy Foundation, NIH R01DK127082 (FMS), DOD GW180072 (MCC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Inspiratory Pressure Threshold Loading: Effects on Inspiratory Pattern, Perception and Prefrontal Cortical Activity
Authors: Miranda Andre , Burt Juliana , Davenport Paul , Davenport Matthew 
Published: May 2024

Cognitive awareness of breathing can lead to behavioral ventilatory compensation, respiratory interoception and activation of brain regions associated with decision processes, including the dorsal prefrontal cortex (dPFC). The dPFC is a critical cortical region mediating executive functions and dPFC activity is modulated during increased breathing load. This study investigated load compensation and perception response to sustained breathing against inspiratory pressure threshold (PT) loads. We hypothesized that increasing magnitudes of PT loads require increasing time to valve opening resulting in; greater inspiratory motor drive, increased perception of breathing effort (INT), increased perception of unpleasantness (UPL) and increased dPFC oxygen consumption (OXY, a measure of increased neural activity). Functional near-infrared spectroscopy (fNIRS) was used to measure OXY changes in the dPFC. Healthy subjects were exposed to 5 cmH2O (LoPT) and 20 cmH2O (HiPT) inspiratory PT loads for 1 minute load-on and 1 minute load-off trials. A total of 8 trials for each load were presented, 4 INT trials and 4 UPL trials. Perception of inspiratory INT and UPL was rated with a 0-10 modified Borg scale. There was a significant PT magnitude dependent increase in valve opening duration (0.18±0.15 LoPT vs 0.57±0.17 HiPT) and pressure (-4.4±0.75 LoPT vs -21.3±2.2 HiPT, p<0.001). The pressure-time-product (PtP), a measure of inspiratory motor drive, significantly (p<0.001) increased with PT magnitude. A significant PT magnitude dependent increase in INT (2.8±1.3 vs 7.9±1.2, p<0.001) and UPL (1.9±1.4 vs 7.8±1.4, p<0.001) ratings occurred but perception ratings did not significantly change throughout the 1-minute trial. The average 1-minute trial OXY LoPT was significantly (p<0.02) less than HiPT. The right dPFC OXY did not significantly change between trial Breath 1 and Breath 10. The left dPFC OXY significantly (p<0.01) increased from trial Breath 1 to Breath 10. These results suggest increased PT load magnitude required greater inspiratory drive to breathe. Breathing against a HiPT load was perceived as highly effortful and unpleasant. Sustained breathing against PT loads progressively increased left dPFC neural activity. Supported by the University of Florida, College of Veterinary Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Day-to-day repeatability of total and regional cerebral blood flow
Authors: Ortiz Andrés , Muer Jessica , Didier Kaylin , Wannebo Brett , Sanchez Sophie , Wieben Oliver , Eldridge Marlowe 
Published: May 2024

Background: Measuring cerebral blood flow (CBF) has been crucial in understanding brain function and health. Most studies use a resting CBF value for comparison when testing different experimental conditions on different days; however, it is unclear whether resting condition values can be repeated between days. This has important implications for intervention or mechanistic studies. We hypothesize that resting CBF will be repeatable across different days in a well-controlled setting using MRI based pseudo-continuous arterial spin labeling (pcASL). Methods: Seven subjects (1F, 6M) were studied on two separate occasions after abstaining from caffeine, NSAIDs and exercise for 24 hours, and fasting for 8 hours. The end tidal CO2 had to be within 2mmHg between visits. Female subjects were on days 1-7 of their menstrual cycle and were not taking any hormonal contraception. CBF was quantified via MRI based pseudo-continuous Arterial Spin Labeling (pcASL) during both visits and expressed relative to gray and white matter (mL/min/100g). Data focuses on total grey matter, total white matter, and 8 emotional and memory regions. The repeatability of all CBF values was tested between both MRI visits using linear regression. Results: Scans were completed 113± 81 days apart. R2 values showed a weak effect size for grey matter (R2 =0.454) and a moderate effect size for white matter (R2 =0.527). When measuring for the 8 regions of the brain, there were no significant p-values, and weak R2 effect size for the accumbens (p=0.107, R2 =0.454), amygdala (p=0.204, R2 =0.299), anterior cingulate (p=0.092, R2 =0.463), caudate (p=0.122, R2 =0.409) hippocampus (p=0.175, R2 =0.332), and parahippocampus (p=0.183, R2 =0.323). In brain regions involved with memory, the entorhinal cortex indicated a R2 value of moderate effect size (p=0.068, R2 =0.519) t (p=0.068), as well as the precuneus (p=0.060, R2 =0.54) Conclusion: The results suggest that resting CBF demonstrates low repeatability between days. Noteworthy trends exist in the entorhinal cortex and precuneus, which both are involved in memory. These findings suggest that when comparing resting CBF, researchers may want to consider collecting new resting CBF measurements every time they are testing for reactivity since there might be variability in areas such as the accumbens, amygdala, anterior cingulate, caudate, hippocampus and parahippocampus. Funding: NIH R01 HL150361. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
A Timeline of Cardiac Maturation
Authors: Mikkila Jennifer , Wang Ruchen , Torniainen Andrea , Nelson Gabrielle , Rajvansh Neal , Meyer Markus , van Berlo Jop 
Published: May 2024

Background: Much is known about the differences between adult and immature fetal cardiac myocytes. For example, the switch from glycolysis to oxidative phosphorylation, the increase in sarcomere distance and cell size, along with changes in mitochondrial structure and organization are all known to occur at some point between late embryonic development and adulthood. However, the precise timing of when these changes take place is ill-defined. Here, we report in high temporal resolution when hallmarks of maturation develop to provide a timeline and the order of events that are necessary for structural and physiological cardiomyocyte maturation. Methods and Results: Using murine samples from embryonic day 15 all the way to adulthood, we performed characterization of basic organelles, contractile machinery, and extracellular matrix composition, all shown to be necessary for cardiac maturation. We observed clear differences in when maturation hallmarks became established. Features that increased continuously include growth of the size of the heart and cardiomyocytes. Accompanying cell size changes, an increase in endothelial cell count was observed, although cardiomyocyte growth continued after the endothelial cell population reached a plateau. Seahorse assays revealed that mitochondrial respiration increased continuously over time for Complex 1 and 2 until about postnatal day 15, with complex 4 being relatively stable throughout maturation. Lipid droplets appeared at a higher frequency in ventricular tissue starting at postnatal day 5, coinciding with an increase in sarcomere length. T-tubules began to appear at postnatal day 7 alongside changes in calcium handling genes. Mitochondrial size was found to increase rapidly at postnatal day 19. Discussion: Overall, we found that multiple stages of development seem important to target for enhancing maturation as not all changes occur in a linear fashion. Ultimately, knowledge of when maturational hallmarks develop might inform strategies to enhance maturation of human induced pluripotent stem cell derived cardiomyocytes. T32 Minnesota Muscle Training Grant; Summer’s Wish; Regenerative Medicine Minnesota; Stem Cell Institute Predoctoral Infuse Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sudden Death Induced by Rapid Intravenous Injection of Fentanyl in Conscious Rats
Authors: Zhuang Jianguo , Gao Xiuping , Shi Shan , Xu Fadi 
Published: May 2024

The sudden death induced by rapid intravenous (IVr) injection of overdose FNT in clinical settings is commonly observed in conscious humans and more often in the males than females. Our previous study has shown that IVr injection of FNT induces a long-lasting apnea associated with bradycardia and hypotension in anesthetized rats (Zhuang et al. 2023 EB). This study aimed to determine whether a lethal dose of FNT could cause sudden death with the mortality being higher in male rats than female ones and whether the FNT-induced respiratory disorder, especially ventilatory arrest, but not cardiac arrest, was the trigger of the death. The rat previously instrumented with ECG electrodes and jugular vein cannulation was placed in a restraint tube that was connected to a plethysmograph chamber to record cardiorespiratory activities. We found that FNT at doses <2 mg/kg induced an immediate persistent apnea, lasting less than 1 min, associated with bradycardia. Following restoration of respiratory rhythm, the rats showed depressed VE and bradycardia for several hours and the cardiorespiratory variables recovered next day. A lethal dose of FNT at 3 mg/kg, compared to FNT at <2 mg/kg, induced an even longer apnea (lasting >1.5 min) accompanied with more severe bradycardia. This sustained apnea was usually interrupted by brief restoration of breathing, which was followed by ventilatory and cardiac arrest occurring at approximately 5 min and 10 min post injection respectively. Although the initial cardiorespiratory response to FNT appeared to be similar in both genders, the death rate was relatively higher in male rats than female ones. In conclusion, our study establishes an animal model of IVr injection of overdose FNT-induced sudden death occurring within minutes. The sudden death is the result of ventilatory, but not cardiac, arrest following a brief restoration of respiratory activity from a sustained apnea. Supported by NIH R01 grants HL163512 and DA059063. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Pressure regulation of L-type Ca2+ channels and its role in myogenic response
Authors: Mironova Galina Yu. , Baudel Miguel Martín-Aragón , Flores-Tamez Victor A. , Brett Suzanne E. , Navedo Manuel F. , Welsh Donald G. 
Published: May 2024

L-type calcium (Ca2+) channels hold a pivotal position in governing intracellular Ca2+ concentration within smooth muscle and the establishment of myogenic tone. Their primary regulatory mechanism has historically been linked to voltage. Nevertheless, it remains a subject of inquiry whether voltage represents the exclusive modulator or whether these channels also exhibit mechanosensitivity. This study seeks to elucidate the influence of pressure stimuli on L-type Ca2+ channels in the resistance arteries of rodents (rats and mice). The investigative approach spans from the scrutiny of individual smooth muscle cells employing methodologies such as whole-cell and cell-attached patch-clamp electrophysiology, immunohistochemistry, proximity ligation assay, and super-resolution microscopy to the evaluation of intact arteries utilizing pressure myography. The findings obtained through whole-cell patch-clamp electrophysiology unveil a notable augmentation in L-type Ca2+ current in response to pressure stimuli. Subsequent scrutiny at the level of single-channel activity discloses that this augmentation is ascribed to an enhancement in functional coupling. Further inquiry reveals that the intensified functional coupling in response to pressure is contingent upon two principal factors: 1) the facilitation of cooperative gating mediated by protein kinase C (PKC), and 2) the traffcking of subunits to caveolae. Notably, functional experiments, involving depolarization elicited through the application of 30 mM KCl, underscore that arterial tone and cytosolic Ca2+ concentration responses are markedly more pronounced when the arteries are subjected to a pressure of 80 mmHg, as opposed to 20 mmHg. The culmination of these observations from both patch-clamp experiments and functional investigations supports the assertion that L-type Ca2+ channels are indeed amenable to mechanosensory influences, in addition to their well-documented voltage-dependent behavior. In summation, this investigation underscores that the regulatory landscape of L-type Ca2+ channels transcends the confines of voltage control, emphasizing the significance of considering pressure sensitivity in both physiological and pathological contexts. Ongoing research endeavors aim to delineate with precision the signaling complexes within vascular smooth muscle that respond to mechanical forces. Supported by the Canadian Institute for Health Research, National Institute of Health and the Rorabeck Chair in Vascular Biology and Neuroscience. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Cross-sexual Effects of Testosterone on Mesenteric Arterial Reactivity in Ovariectomized Female Rats
Authors: Rahman Mohammad Moshiur , Islam Rifat Ara , Razan Md Rahatullah , Esfandiarei Mitra , Felmlee Melanie , Rahimian Roshanak 
Published: May 2024

The number of transgender individuals is on the rise in the United States. Although there are studies on the effects of sex hormones on cardiovascular function of cisgender male and female, still much is not known about the effects of cross-sex hormone therapy (CSHT) on cardiovascular function in transgender individuals. It has been shown that the risk factors of cardiovascular diseases (CVD) are increased in transgenders after they undergo CSHT. Epidemiological studies suggest that transgender females (male to female, MtF) on estrogen therapy develop higher risk of CVD compared to transgender males (female to male, FtM) taking testosterone. This study investigates the effects of testosterone or estrogen treatment on the third branch of mesenteric arterial reactivity in ovariectomized female rats. Briefly, 8-10 weeks old female Sprague Dawley (SD) rats were ovariectomized (OVX) and subcutaneously implanted with placebo (OVX + PL) or testosterone (OVX + T, 7.5 mg) or 17β- estradiol (OVX + E2, 1.5 mg) pellets for about 35 days. Age matched intact female SD rats were also included in the experimental groups. Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh) was measured in the precontracted mesenteric arteries with phenylephrine (PE), using wire myography. Responses to sodium nitroprusside (SNP)-induced vasorelaxation, and PE- and endothelin-1 (ET-1) induced vasocontraction were also determined. We demonstrated that the responses to ACh in rat mesenteric arteries were not altered by either ovariectomy or estrogen treatment. However, testosterone treatment of OVX female rats significantly enhanced the sensitivity to ACh-induced vasorelaxation compared with those in other experimental groups. Moreover, the mesenteric arteries of OVX + T exhibited a trend of reduced sensitivity to PE responses compared to other groups. Furthermore, the maximum tension to ET-1 was significantly reduced in mesenteric arteries of OVX + T compared to OVX+E2 and OVX+PL groups. The vasorelaxation responses to SNP were not altered in any of experimental groups studied. These data suggest that elevated sensitivity to ACh in testosterone-treated ovariectomized female rats might be, in part, due to reduced vessel responses to contractile agents, but not altered sensitivity of smooth muscle to nitric oxide (NO) in this group. Additional studies are needed to investigate the underlying mechanisms and document the consequences for the improvement of EDV observed in OVX + T rats. NIDA/NIGMS, 1SC1DA052120-01 to MF, Bridge Grant from University of the Pacific to RR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.