scholarly journals In vivo cardiopulmonary impact of skeletal M3Dq DREADD expression: a pilot study

2021 ◽  
Author(s):  
Sandra G. Vincent ◽  
John T. Fisher
Keyword(s):  
Heart Rate ◽  
Cardiac Arrhythmias ◽  
Striated Muscle ◽  
Minute Ventilation ◽  
Control Period ◽  
Designer Drug ◽  
Significant Drop ◽  
Concomitant Reduction ◽  
G Protein Coupled

AbstractThe muscarinic M3 receptor (M3R) is implicated in cardiopulmonary control and many other peripheral physiologic functions. Previous observations report mortality in mice expressing a Gq-linked designer G-protein coupled receptor (Dq) selectively in striated muscle, while M3Dq DREADD (Designer Receptor Exclusively Activated by Designer Drug), selectively expressed in skeletal muscle (SKM) impacts glucose metabolism. We investigated whether activation of SKM M3Dq impacts cardiopulmonary function. Heart rate (HR), body temperature (Tb) and locomotor activity (ACT) were measured in 4 conscious, chronically instrumented M3Dq DREADD mice and 4 wildtype controls. Circadian values of HR, BT and ACT were not different between genotypes (p > 0.05). Activation of the M3Dq DREADD by clozapine N-oxide (CNO; 0.1 mg/kg) resulted in: a significant drop in heart rate, 2 h after injection, compared with a time-matched baseline control period from the same animals (460 ± 28 vs. 532 ± 6, p < 0.05), significantly lower ACT compared to the baseline control (p < 0.05) and reduced pulmonary minute ventilation compared to pre-CNO control (p < 0.05). M3Dq DREADD activation did not cause bronchoconstriction (separate protocol), however, there was a concomitant reduction in HR, Tb and ventilation, accompanied by cardiac arrhythmias. We speculate that reductions in Tb, HR and ventilation reflect a mechanistic link between SKM Gq signaling and the metabolic responses associated with the initiation of torpor. Supported by the Canadian Institutes of Health Research (CIHR MOP-81211).

Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans

1990 ◽  
Vol 69 (3) ◽  
pp. 907-913 ◽  
Author(s):  
N. B. Hampson ◽  
E. M. Camporesi ◽  
B. W. Stolp ◽  
R. E. Moon ◽  
J. E. Shook ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Volume ◽  
Near Infrared ◽  
Cerebral Blood Volume ◽  
Minute Ventilation ◽  
Nir Spectroscopy ◽  
Redox Status ◽  
Total Blood ◽  
Arterial Ph

The effects of mild hypoxia on brain oxyhemoglobin, cytochrome a,a3 redox status, and cerebral blood volume were studied using near-infrared spectroscopy in eight healthy volunteers. Incremental hypoxia reaching 70% arterial O2 saturation was produced in normocapnia [end-tidal PCO2 (PETCO2) 36.9 +/- 2.6 to 34.9 +/- 3.4 Torr] or hypocapnia (PETCO2 32.8 +/- 0.6 to 23.7 +/- 0.6 Torr) by an 8-min rebreathing technique and regulation of inspired CO2. Normocapnic hypoxia was characterized by progressive reductions in arterial PO2 (PaO2, 89.1 +/- 3.5 to 34.1 +/- 0.1 Torr) with stable PETCO2, arterial PCO2 (PaCO2), and arterial pH and resulted in increases in heart rate (35%) systolic blood pressure (14%), and minute ventilation (5-fold). Hypocapnic hypoxia resulted in progressively decreasing PaO2 (100.2 +/- 3.6 to 28.9 +/- 0.1 Torr), with progressive reduction in PaCO2 (39.0 +/- 1.6 to 27.3 +/- 1.9 Torr), and an increase in arterial pH (7.41 +/- 0.02 to 7.53 +/- 0.03), heart rate (61%), and ventilation (3-fold). In the brain, hypoxia resulted in a steady decline of cerebral oxyhemoglobin content and a decrease in oxidized cytochrome a,a3. Significantly greater loss of oxidized cytochrome a,a3 occurred for a given decrease in oxyhemoglobin during hypocapnic hypoxia relative to normocapnic hypoxia. Total blood volume response during hypoxia also was significantly attenuated by hypocapnia, because the increase in volume was only half that of normocapnic subjects. We conclude that cytochrome a,a3 oxidation level in vivo decreases at mild levels of hypoxia. PaCO is an important determinant of brain oxygenation, because it modulates ventilatory, cardiovascular, and cerebral O2 delivery responses to hypoxia.

Contractile parameters and occurrence of alternans in isolated rat myocardium at supra-physiological stimulation frequency

2012 ◽  
Vol 302 (11) ◽  
pp. H2267-H2275 ◽  
Author(s):  
Jessica L. Slabaugh ◽  
Lucia Brunello ◽  
Sandor Gyorke ◽  
Paul M. L. Janssen
Keyword(s):  
Heart Rate ◽  
Steady State ◽  
Refractory Period ◽  
Striated Muscle ◽  
Stable Steady State ◽  
Maximal Heart Rate ◽  
Force Frequency ◽  
Mechanical Instability ◽  
Continuous Increase

The cardiac refractory period prevents the heart from tetanic activation that is typically used in noncardiac striated muscle tissue. To what extent the refractory period prevents successive action potentials to activate the excitation-contraction coupling process and contractile machinery at supra-physiological rates, such as those present during ventricular fibrillation, is unknown. Using multicellular trabeculae isolated from rat hearts, we studied amplitude and kinetics of contraction at rates well above the normal in vivo rat heart range. We show that even at twice the maximal heart rate of the rat, little or no mechanical instability is observed; twitch contractions are at steady state, albeit with an elevated active diastolic force. Although the amplitude of contraction increased within in vivo heart rates (positive force-frequency response), at frequencies beyond the maximal heart rate (10–30 Hz) a steady decline of contractile amplitude is observed. Not until 30 Hz do the majority of the isolated muscle preparations show mechanical alternans, where strong and weak beats alternate. Interestingly, unlike striated limb skeletal muscle, fusing of twitch contractions did not cause a continuous increase in peak force: at frequencies of 10 Hz and above, systolic force declines with relatively little elevation in diastolic force. Contractile kinetics continued to accelerate, from 1 Hz up to 30 Hz, whereas the relative speed of contraction and relaxation remained closely coupled, reflected by a singular linear relationship between the maximal and minimal derivative of force (dF/d t). We conclude that cardiac muscle can produce mechanically stable steady-state contractions at supra-physiological pacing rates, while these contractions continue to decline in amplitude and increase in diastolic force past maximal heart rate.

scholarly journals G protein-coupled estrogen receptor regulates heart rate by modulating thyroid hormone levels in zebrafish embryos

2016 ◽  
Author(s):  
Shannon N Romano ◽  
Hailey E Edwards ◽  
Xiangqin Cui ◽  
Daniel A Gorelick
Keyword(s):  
Heart Rate ◽  
Estrogen Receptor ◽  
Thyroid Hormone ◽  
G Protein ◽  
Sex Differentiation ◽  
Zebrafish Embryos ◽  
Basal Heart Rate ◽  
Normal Heart Rate ◽  
G Protein Coupled

AbstractEstrogens act by binding to estrogen receptors alpha and beta (ERα, ERβ), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos. Acute exposure to estrogens increased heart rate in wildtype and in ERα and ERβ mutant embryos but not in GPER mutants. GPER mutant embryos exhibited reduced basal heart rate, while heart rate was normal in ERα and ERβ mutants. We detected gper transcript in discrete regions of the brain and pituitary but not in the heart, suggesting that GPER acts centrally to regulate heart rate. In the pituitary, we observed gper expression in cells that regulate levels of thyroid hormone triiodothyronine (T3), a hormone known to increase heart rate. GPER mutant embryos showed a mean 50% reduction in T3 levels compared to wildtype, while exposure to exogenous T3 rescued the reduced heart rate phenotype in GPER mutants. Our results demonstrate that estradiol plays a previously unappreciated role in the acute modulation of heart rate during zebrafish embryonic development and suggest that GPER regulates basal heart rate by altering total T3 levels.

scholarly journals The Impact of COVID-19 Pandemic and Lockdown Restrictions on Cardiac Implantable Device Recipients with Remote Monitoring

2021 ◽  
Vol 10 (23) ◽  
pp. 5626
Author(s):  
Igor Diemberger ◽  
Alessandro Vicentini ◽  
Giuseppe Cattafi ◽  
Matteo Ziacchi ◽  
Saverio Iacopino ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Negative Impact ◽  
Control Period ◽  
Cardiac Resynchronization ◽  
Infection Prevalence ◽  
Healthcare Organizations ◽  
Significant Drop ◽  
Low Prevalence ◽  
The Impact

From 2020, many countries have adopted several restrictions to limit the COVID-19 pandemic. The forced containment impacted on healthcare organizations and the everyday life of patients with heart disease. We prospectively analyzed data recorded from implantable defibrillators and/or cardiac resynchronization devices of Italian patients during the lockdown (LDP), post-lockdown period (PLDP) and a control period (CP) of the previous year. We analyzed device data of the period 9 March 2019–31 May 2020 of remotely monitored patients from 34 Italian centers. Patients were also categorized according to areas with high/low infection prevalence. Among 696 patients, we observed a significant drop in median activity in LDP as compared to CP that significantly increased in the PLDP, but well below CP (all p < 0.0001). The median day heart rate and heart rate variability showed a similar trend. This behavior was associated during LDP with a significant increase in the burden of atrial arrhythmias (p = 0.0150 versus CP) and of ventricular arrhythmias [6.6 vs. 1.5 per 100 patient-weeks in CP; p = 0.0026]; the latter decreased in PLDP [0.3 per 100 patient-weeks; p = 0.0035 vs. LDP]. No modifications were recorded in thoracic fluid levels. The high/low prevalence of COVID-19 infection had no significant impact. We found an increase in the arrhythmic burden in LDP coupled with a decrease in physical activity and heart rate variability, without significant modifications of transthoracic impedance, independent from COVID-19 infection prevalence. These findings suggest a negative impact of the COVID-19 pandemic, probably related to lockdown restrictions.

A Review on Melatonin’s Effects in Cancer: Potential Mechanisms

2018 ◽  
Vol 18 (7) ◽  
pp. 985-992 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Ertan Kucuksayan ◽  
Rana Cagla Akduman ◽  
Tomris Ozben
Keyword(s):  
Systematic Review ◽  
Antioxidant Activity ◽  
Membrane Receptors ◽  
Cancer Development ◽  
Secretory Product ◽  
Prevention And Treatment ◽  
G Protein Coupled

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.

scholarly journals Gpr1 is an active chemerin receptor influencing glucose homeostasis in obese mice

2014 ◽  
Vol 222 (2) ◽  
pp. 201-215 ◽  
Author(s):  
Jillian L Rourke ◽  
Shanmugam Muruganandan ◽  
Helen J Dranse ◽  
Nichole M McMullen ◽  
Christopher J Sinal
Keyword(s):  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Stromal Vascular Fraction ◽  
Tolerance Test ◽  
Glucose Levels ◽  
Brown Adipose ◽  
Elevated Glucose ◽  
And Function ◽  
G Protein Coupled

Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murineGpr1mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) andCmklr1,Gpr1expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygousGpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lackingGpr1exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects ofGpr1deficiency on adiposity, energy balance, and glucose homeostasisin vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity.

scholarly journals A Region of the Myosin Rod Important for Interaction With Paramyosin in Caenorhabditis elegans Striated Muscle

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 631-643
Author(s):  
Pamela E Hoppe ◽  
Robert H Waterston
Keyword(s):  
Caenorhabditis Elegans ◽  
Heavy Chain ◽  
Molecular Interaction ◽  
Striated Muscle ◽  
Genetic Interaction ◽  
Specific Interaction ◽  
Thick Filament ◽  
Parallel Arrangement ◽  
Myosin Rod

Abstract The precise arrangement of molecules within the thick filament, as well as the mechanisms by which this arrangement is specified, remains unclear. In this article, we have exploited a unique genetic interaction between one isoform of myosin heavy chain (MHC) and paramyosin in Caenorhabditis elegans to probe the molecular interaction between MHC and paramyosin in vivo. Using chimeric myosin constructs, we have defined a 322-residue region of the MHC A rod critical for suppression of the structural and motility defects associated with the unc-15(e73) allele. Chimeric constructs lacking this region of MHC A either fail to suppress, or act as dominant enhancers of, the e73 phenotype. Although the 322-residue region is required for suppression activity, our data suggest that sequences along the length of the rod also play a role in the isoform-specific interaction between MHC A and paramyosin. Our genetic and cell biological analyses of construct behavior suggest that the 322-residue region of MHC A is important for thick filament stability. We present a model in which this region mediates an avid interaction between MHC A and paramyosin in parallel arrangement in formation of the filament arms.

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