scholarly journals The Long-Term Effects of Developmental Hypoxia on Cardiac Mitochondrial Function in Snapping Turtles

2021 ◽  
Vol 12 ◽  
Author(s):  
Gina L. J. Galli ◽  
Ilan M. Ruhr ◽  
Janna Crossley ◽  
Dane A. Crossley
Keyword(s):  
Embryonic Development ◽  
Mitochondrial Function ◽  
Hypoxia Tolerance ◽  
Breath Hold ◽  
Ros Production ◽  
Long Term Effects ◽  
Anoxic Environments ◽  
The Common ◽  
Mitochondrial Remodeling

It is well established that adult vertebrates acclimatizing to hypoxic environments undergo mitochondrial remodeling to enhance oxygen delivery, maintain ATP, and limit oxidative stress. However, many vertebrates also encounter oxygen deprivation during embryonic development. The effects of developmental hypoxia on mitochondrial function are likely to be more profound, because environmental stress during early life can permanently alter cellular physiology and morphology. To this end, we investigated the long-term effects of developmental hypoxia on mitochondrial function in a species that regularly encounters hypoxia during development—the common snapping turtle (Chelydra serpentina). Turtle eggs were incubated in 21% or 10% oxygen from 20% of embryonic development until hatching, and both cohorts were subsequently reared in 21% oxygen for 8 months. Ventricular mitochondria were isolated, and mitochondrial respiration and reactive oxygen species (ROS) production were measured with a microrespirometer. Compared to normoxic controls, juvenile turtles from hypoxic incubations had lower Leak respiration, higher P:O ratios, and reduced rates of ROS production. Interestingly, these same attributes occur in adult vertebrates that acclimatize to hypoxia. We speculate that these adjustments might improve mitochondrial hypoxia tolerance, which would be beneficial for turtles during breath-hold diving and overwintering in anoxic environments.

scholarly journals Developmental plasticity of cardiac anoxia-tolerance in juvenile common snapping turtles ( Chelydra serpentina )

2019 ◽  
Vol 286 (1905) ◽  
pp. 20191072 ◽  
Author(s):  
Ilan M. Ruhr ◽  
Heather McCourty ◽  
Afaf Bajjig ◽  
Dane A. Crossley ◽  
Holly A. Shiels ◽  
...  
Keyword(s):  
Developmental Plasticity ◽  
Hypoxia Tolerance ◽  
Anoxia Tolerance ◽  
Ros Production ◽  
Oxygen Species ◽  
Early Exposure ◽  
Cellular Mechanisms ◽  
Isolated Cardiomyocytes ◽  
Intracellular Ca ◽  
The Common

For some species of ectothermic vertebrates, early exposure to hypoxia during embryonic development improves hypoxia-tolerance later in life. However, the cellular mechanisms underlying this phenomenon are largely unknown. Given that hypoxic survival is critically dependent on the maintenance of cardiac function, we tested the hypothesis that developmental hypoxia alters cardiomyocyte physiology in a manner that protects the heart from hypoxic stress. To test this hypothesis, we studied the common snapping turtle, which routinely experiences chronic developmental hypoxia and exploits hypoxic environments in adulthood. We isolated cardiomyocytes from juvenile turtles that embryonically developed in either normoxia (21% O 2 ) or hypoxia (10% O 2 ), and subjected them to simulated anoxia and reoxygenation, while simultaneously measuring intracellular Ca 2+ , pH and reactive oxygen species (ROS) production. Our results suggest developmental hypoxia improves cardiomyocyte anoxia-tolerance of juvenile turtles, which is supported by enhanced myofilament Ca 2+ -sensitivity and a superior ability to suppress ROS production. Maintenance of low ROS levels during anoxia might limit oxidative damage and a greater sensitivity to Ca 2+ could provide a mechanism to maintain contractile force. Our study suggests developmental hypoxia has long-lasting effects on turtle cardiomyocyte function, which might prime their physiology for exploiting hypoxic environments.

Integrating the patient (pt) voice with clinician reports to identify cancer-specific subsets of symptomatic adverse events (SymAE).

2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 155-155
Author(s):  
Jim Shaw ◽  
Rebecca Speck ◽  
William Lenderking ◽  
Caroleen Quach
Keyword(s):  
Clinical Trial Data ◽  
Long Term Effects ◽  
Qualitative And Quantitative ◽  
Medical Oncologists ◽  
Bowel Movements ◽  
Hand Foot Syndrome ◽  
Cancer Care Continuum ◽  
Pugh Class ◽  
The Common

155 Background: The Pt-Reported Outcomes Version of the Common Terminology Criteria for AE (PRO-CTCAE) was developed for pts to report on the frequency, severity, and interference of SymAE. A study was conducted to identify a hepatocellular carcinoma (HCC)-relevant subset of the PRO-CTCAE's 124 items to enhance evaluation of SymAE in HCC trials and long-term effects in survivorship. Methods: Qualitative and quantitative data were collected from medical oncologists specializing in HCC and pts diagnosed with HCC stratified by Child-Pugh class and treatment. Oncologists were asked about HCC diagnosis, treatment, and SymAE and provided ratings (ranging from 0 = unimportant to 10 = very important) of the following: 1) importance to pts of 34 prevalent SymAE from past HCC trials (all phases); 2) importance to pts of each PRO-CTCAE item; and 3) their own perceived importance of each PRO-CTCAE item with regard to tolerability. Pts were asked about their diagnosis, treatment, and experience of SymAE after which they completed the PRO-CTCAE and were debriefed on the importance of each item. Results: Four medical oncologists from Spain, Taiwan, Korea, and Hong Kong with ≥ 20 years of experience completed interviews. SymAE from prior trials rated highly important to pts (mean rating across oncologists ≥ 7) included hand-foot syndrome, diarrhea, fatigue, decreased appetite, rash, vomiting, and weight loss. PRO-CTCAE items rated highly important to pts included diarrhea, vomiting, shivering or shaking chills, hand-foot syndrome, rash, fatigue, difficulty swallowing, and loss of control of bowel movements. Items rated highly for tolerability included diarrhea, shivering or shaking chills, and hand-foot syndrome. Pt interviews (planned up to 24) are ongoing. Conclusions: Oncologists identified 10 clinically relevant items from sponsor SymAE data and the PRO-CTCAE for use in HCC trials. Findings from pt interviews will compare provider and pt perspectives about SymAE and strengthen the set of selected items. Combining clinician and pt ratings with clinical trial data may be a promising method for identifying cancer-specific PRO-CTCAE item sets for use throughout the cancer care continuum.

scholarly journals Phenotypic plasticity in the common snapping turtle (Chelydra serpentina): long-term physiological effects of chronic hypoxia during embryonic development

2016 ◽  
Vol 310 (2) ◽  
pp. R176-R184 ◽  
Author(s):  
Oliver H. Wearing ◽  
John Eme ◽  
Turk Rhen ◽  
Dane A. Crossley
Keyword(s):  
Chronic Hypoxia ◽  
Common Garden ◽  
Physiological Effects ◽  
Chelydra Serpentina ◽  
Long Term Effects ◽  
Snapping Turtle ◽  
Snapping Turtles ◽  
The Common ◽  
Hypoxic Incubation

Studies of embryonic and hatchling reptiles have revealed marked plasticity in morphology, metabolism, and cardiovascular function following chronic hypoxic incubation. However, the long-term effects of chronic hypoxia have not yet been investigated in these animals. The aim of this study was to determine growth and postprandial O2 consumption (V̇o2), heart rate ( fH), and mean arterial pressure ( Pm, in kPa) of common snapping turtles ( Chelydra serpentina) that were incubated as embryos in chronic hypoxia (10% O2, H10) or normoxia (21% O2, N21). We hypothesized that hypoxic development would modify posthatching body mass, metabolic rate, and cardiovascular physiology in juvenile snapping turtles. Yearling H10 turtles were significantly smaller than yearling N21 turtles, both of which were raised posthatching in normoxic, common garden conditions. Measurement of postprandial cardiovascular parameters and O2 consumption were conducted in size-matched three-year-old H10 and N21 turtles. Both before and 12 h after feeding, H10 turtles had a significantly lower fH compared with N21 turtles. In addition, V̇o2 was significantly elevated in H10 animals compared with N21 animals 12 h after feeding, and peak postprandial V̇o2 occurred earlier in H10 animals. Pm of three-year-old turtles was not affected by feeding or hypoxic embryonic incubation. Our findings demonstrate that physiological impacts of developmental hypoxia on embryonic reptiles continue into juvenile life.

scholarly journals Physiology, pathophysiology and (mal)adaptations to chronic apnoeic training: a state-of-the-art review

2021 ◽  
Author(s):  
Antonis Elia ◽  
M. Gennser ◽  
P. S. Harlow ◽  
Matthew J. Lees
Keyword(s):  
Preliminary Evidence ◽  
Breath Holding ◽  
Breath Hold ◽  
Long Term Effects ◽  
Diving Response ◽  
Recreational Sport ◽  
Modern Times ◽  
Military Campaigns ◽  
World Records

AbstractBreath-hold diving is an activity that humans have engaged in since antiquity to forage for resources, provide sustenance and to support military campaigns. In modern times, breath-hold diving continues to gain popularity and recognition as both a competitive and recreational sport. The continued progression of world records is somewhat remarkable, particularly given the extreme hypoxaemic and hypercapnic conditions, and hydrostatic pressures these athletes endure. However, there is abundant literature to suggest a large inter-individual variation in the apnoeic capabilities that is thus far not fully understood. In this review, we explore developments in apnoea physiology and delineate the traits and mechanisms that potentially underpin this variation. In addition, we sought to highlight the physiological (mal)adaptations associated with consistent breath-hold training. Breath-hold divers (BHDs) are evidenced to exhibit a more pronounced diving-response than non-divers, while elite BHDs (EBHDs) also display beneficial adaptations in both blood and skeletal muscle. Importantly, these physiological characteristics are documented to be primarily influenced by training-induced stimuli. BHDs are exposed to unique physiological and environmental stressors, and as such possess an ability to withstand acute cerebrovascular and neuronal strains. Whether these characteristics are also a result of training-induced adaptations or genetic predisposition is less certain. Although the long-term effects of regular breath-hold diving activity are yet to be holistically established, preliminary evidence has posed considerations for cognitive, neurological, renal and bone health in BHDs. These areas should be explored further in longitudinal studies to more confidently ascertain the long-term health implications of extreme breath-holding activity.

scholarly journals Tissue-Specific Effects of Bariatric Surgery Including Mitochondrial Function

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Simon N. Dankel ◽  
Vidar Staalesen ◽  
Bodil Bjørndal ◽  
Rolf K. Berge ◽  
Gunnar Mellgren ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Mitochondrial Function ◽  
Metabolic Regulation ◽  
Protein Profile ◽  
Metabolic Parameters ◽  
Acute Effects ◽  
Long Term Effects ◽  
Short Term ◽  
Specific Effects

A better understanding of the molecular links between obesity and disease is potentially of great benefit for society. In this paper we discuss proposed mechanisms whereby bariatric surgery improves metabolic health, including acute effects on glucose metabolism and long-term effects on metabolic tissues (adipose tissue, skeletal muscle, and liver) and mitochondrial function. More short-term randomized controlled trials should be performed that include simultaneous measurement of metabolic parameters in different tissues, such as tissue gene expression, protein profile, and lipid content. By directly comparing different surgical procedures using a wider array of metabolic parameters, one may further unravel the mechanisms of aberrant metabolic regulation in obesity and related disorders.

scholarly journals Testing the short-and long-term effects of elevated prenatal exposure to different forms of thyroid hormones

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10175
Author(s):  
Tom Sarraude ◽  
Bin-Yan Hsu ◽  
Ton Groothuis ◽  
Suvi Ruuskanen
Keyword(s):  
Oxidative Stress ◽  
Embryonic Development ◽  
Thyroid Hormones ◽  
Hatching Success ◽  
Long Term Effects ◽  
Short Term ◽  
Short And Long Term ◽  
Long Term Consequences ◽  
And Oxidative Stress

Maternal thyroid hormones (THs) are known to be crucial in embryonic development in humans, but their influence on other, especially wild, animals remains poorly understood. So far, the studies that experimentally investigated the consequences of maternal THs focused on short-term effects, while early organisational effects with long-term consequences, as shown for other prenatal hormones, could also be expected. In this study, we aimed at investigating both the short- and long-term effects of prenatal THs in a bird species, the Japanese quail Coturnix japonica. We experimentally elevated yolk TH content (the prohormone T4, and its active metabolite T3, as well as a combination of both hormones). We analysed hatching success, embryonic development, offspring growth and oxidative stress as well as their potential organisational effects on reproduction, moult and oxidative stress in adulthood. We found that eggs injected with T4 had a higher hatching success compared with control eggs, suggesting conversion of T4 into T3 by the embryo. We detected no evidence for other short-term or long-term effects of yolk THs. These results suggest that yolk THs are important in the embryonic stage of precocial birds, but other short- and long-term consequences remain unclear. Research on maternal THs will greatly benefit from studies investigating how embryos use and respond to this maternal signalling. Long-term studies on prenatal THs in other taxa in the wild are needed for a better understanding of this hormone-mediated maternal pathway.

scholarly journals Angiotensin II Type 1 Receptor Agonistic Autoantibody Blockade Improves Postpartum Hypertension and Cardiac Mitochondrial Function in Rat Model of Preeclampsia

2021 ◽  
Author(s):  
George W. Booz ◽  
Daniel Kennedy ◽  
Michael Bowling ◽  
Taprieka Robinson ◽  
Daniel Azubuike ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Rat Model ◽  
Mitochondrial Function ◽  
Type I ◽  
Sprague Dawley ◽  
Long Term Effects ◽  
Amino Acid Peptide ◽  
Uterine Perfusion

Abstract Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2 years postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence (‘n7AAc’) improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into 3 groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP+‘n7AAc’ (n = 16). Gestational day 14, RUPP surgery was performed and ‘n7AAc’ (144 µg/day) administered via osmotic minipump. At 10 weeks PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs NP (126 ± 4 vs. 116 ± 3 mmHg, p < 0.05), but was normalized in in RUPP+‘n7AAc’ (109 ± 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP+’n7AAc’ vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs NP rats which was prevented with ‘n7AAc’. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP.

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