scholarly journals Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age‐associated alterations in heart rate variability in vivo

Aging Cell ◽  
2016 ◽  
Vol 15 (4) ◽  
pp. 716-724 ◽  
Author(s):  
Yael Yaniv ◽  
Ismayil Ahmet ◽  
Kenta Tsutsui ◽  
Joachim Behar ◽  
Jack M. Moen ◽  
...  
2019 ◽  
Vol 64 ◽  
pp. 16-23
Author(s):  
Jennifer Lara Maria Mumm ◽  
Lena Pyrkosch ◽  
Jens Plag ◽  
Patrick Nagel ◽  
Moritz Bruno Petzold ◽  
...  

2002 ◽  
Vol 282 (2) ◽  
pp. H445-H456 ◽  
Author(s):  
Josef Gehrmann ◽  
Michael Meister ◽  
Colin T. Maguire ◽  
Donna C. Martins ◽  
Peter E. Hammer ◽  
...  

Acetylcholine released on parasympathetic stimulation slows heart rate through activation of muscarinic receptors on the sinus nodal cells and subsequent opening of the atrial muscarinic potassium channel (KACh). KACh is directly activated by G protein βγ-subunits. To elucidate the physiological role of Gβγ for the regulation of heart rate and electrophysiological function in vivo, we created transgenic mice with a reduced amount of membrane-bound Gβ protein by overexpressing nonprenylated Gγ2-subunits in their hearts using the α-myosin heavy chain promoter. At baseline and after muscarinic stimulation with carbachol, heart rate and heart rate variability were determined with electrocardiogram telemetry in conscious mice and in vivo intracardiac electrophysiological studies in anesthetized mice. Reduction of the amount of functional Gβγ protein by >50% caused a pronounced blunting of the carbachol-induced bradycardia as well as the increases in time- and frequency-domain indexes of heart rate variability and baroreflex sensitivity that were observed in wild types. In addition, sinus node recovery time and inducibility of atrial arrhythmias were reduced in transgenic mice. Our data demonstrate in vivo that Gβγ plays a crucial role for parasympathetic heart rate control, sinus node automaticity, and atrial arrhythmia vulnerability.


Shock ◽  
2010 ◽  
Vol 33 (4) ◽  
pp. 363-368 ◽  
Author(s):  
Badar U. Jan ◽  
Susette M. Coyle ◽  
Marie A. Macor ◽  
Michael Reddell ◽  
Steve E. Calvano ◽  
...  

Shock ◽  
2009 ◽  
pp. 1 ◽  
Author(s):  
Badar U. Jan ◽  
Susette M. Coyle ◽  
Marie A. Macor ◽  
Michael Reddell ◽  
Steve E. Calvano ◽  
...  

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Björn Kralemann ◽  
Matthias Frühwirth ◽  
Arkady Pikovsky ◽  
Michael Rosenblum ◽  
Thomas Kenner ◽  
...  

Author(s):  
Rama Lakshman ◽  
Ana-Mishel Spiroski ◽  
Lauren B. McIver ◽  
Michael P. Murphy ◽  
Dino A. Giussani

Work in preclinical animal models has established that pregnancy complicated by chronic fetal hypoxia and oxidative stress programmes cardiovascular dysfunction in adult offspring. Translating this to the human condition comes with challenges, including the early diagnosis of affected individuals to improve clinical outcomes. We hypothesize that components of programmed cardiovascular dysfunction in offspring can be identified in vivo via analysis of blood pressure variability and heart rate variability and that maternal treatment with the mitochondria-targeted antioxidant MitoQ is protective. Pregnant rats were exposed to normoxia or hypoxia (13% O 2 ) ±MitoQ (500 μM in water), from 6 to 20 days gestation. Offspring were maintained in normoxia postnatally. At 16 weeks of age, 1 male per litter was instrumented with vascular catheters and a femoral blood flow probe under isoflurane anesthesia. After recovery, arterial blood pressure and femoral flow were recorded in conscious, free-moving rats and analyzed. Offspring of hypoxic pregnancy had (1) increased very-low-frequency blood pressure variability (A) and heart rate variability (B), indices consistent with impaired endothelial function and (2) increased heart rate variability low/high-frequency ratio (C) and low-frequency blood pressure variability (D), indices of cardiac and vascular sympathetic hyperreactivity, respectively. MitoQ ameliorated A and B but not C and D. We show that asymptomatic cardiovascular dysfunction in adult offspring programmed by hypoxic pregnancy can be diagnosed in vivo by blood pressure variability and heart rate variability, suggesting that these noninvasive biomarkers could be translated to the clinical setting. MitoQ protected against programmed endothelial dysfunction but not sympathetic hyperreactivity, highlighting the divergent programming mechanisms involved.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Stefanie Fenske ◽  
Vanessa Marks ◽  
Stefanie Koenigsbauer ◽  
Sami I Hassan ◽  
Tilman Ziegler ◽  
...  

The heart beat is initiated by the generation of spontaneous action potentials in pacemaker cells of the sinoatrial node (SAN) region. The maintenance of a stable heart beat requires mechanisms which protect the SAN pacemaker cells from potential perturbing influences which arise from inside and outside the sinoatrial network. Our previous work suggests that the hyperpolarization-activated cyclic nucleotide gated channel subtype 1 (HCN1) protects against such perturbations and thereby increases the stability, the precision and the safety of the sinoatrial network. Here, we investigate the role of HCN4 channels within this context. Using genetic mouse models deficient for HCN channels as well as mouse models expressing engineered HCN channels, we performed a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparations, with telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology. We provide evidence that HCN4 has a critical role in counteracting and balancing potentially destabilizing effects of the autonomic nervous system on the regulation of the heart rate. Specifically, HCN4 channels smooth the transition of the heart rate to a new equilibrium. Furthermore, we provide evidence that the cAMP- dependent fine tuning of HCN4 channel activity could provide the exact dosage of current to balance and counteract overshooting responses of the heart rate to autonomic regulation. In the absence of such a protecting effect, mice display a brady- tachy syndrome.


2019 ◽  
Author(s):  
William Ryan ◽  
James Conigrave ◽  
Geetanjali Basarkod ◽  
Joseph Ciarrochi ◽  
Baljinder K. Sahdra

Objective: Recent technological advances have led to the proliferation of ambulatory devices for non-invasively assessing cardiac activity. While these devices have exciting implications for conducting research outside the laboratory, it is critical that this increased mobility does not compromise data quality. As a test case, we assess the efficacy of Empatica’s E4, a high-end wristband device designed to assess Heart Rate Variability (HRV) through the use of photoplethysmography. Approach: We compare the E4 to traditional, wired electrocardiogram measures across a variety of conditions, including seated, supine, and standing baselines, as well as typing and grip strength tasks. Most importantly, we introduce and demonstrate the efficacy of a new method for determining the amount of error in HRV estimates derived from the E4 and a technique for adjusting error tolerance. Main Results: Results indicate that the E4 is severely compromised by motion artifact, resulting in a high percentage of missing data across all conditions except seated and supine baselines. Employing error adjustment yielded more robust results, but at the cost of significantly reducing sample size where motion artifact was present. Significance: These results call into question the wristband’s efficacy as an HRV measurement tool in most in-vivo conditions. We recommend that researchers interested in using photoplethysmography-based HRV devices use caution and evaluate the data quality using methods for error detection and tolerance, such as the one presented here.Keywords: heart rate variability, ambulatory photoplethysmography, electrocardiogram.


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