scholarly journals Nkx2.5 is essential to establish normal heart rate variability in the zebrafish embryo

2017 ◽  
Vol 313 (3) ◽  
pp. R265-R271 ◽  
Author(s):  
Jamie K. Harrington ◽  
Robert Sorabella ◽  
Abigail Tercek ◽  
Joseph R. Isler ◽  
Kimara L. Targoff

Heart rate variability (HRV) has become an important clinical marker of cardiovascular health and a research measure for the study of the cardiac conduction system and its autonomic controls. While the zebrafish ( Danio rerio) is an ideal vertebrate model for understanding heart development, HRV has only recently been investigated in this system. We have previously demonstrated that nkx2.5 and nkx2.7, two homologues of Nkx2–5 expressed in zebrafish cardiomyocytes, play vital roles in maintaining cardiac chamber-specific characteristics. Given observed defects in ventricular and atrial chamber identities in nkx2.5−/− embryos coupled with conduction system abnormalities in murine models of Nkx2.5 insufficiency, we postulated that reduced HRV would serve as a marker of poor cardiac health in nkx2.5 mutants and in other zebrafish models of human congenital heart disease. Using live video image acquisition, we derived beat-to-beat intervals to compare HRV in wild-type and nkx2.5−/− embryos. Our data illustrate that the nkx2.5 loss-of-function model exhibits increased heart rate and decreased HRV when compared with wild type during embryogenesis. These findings validate HRV analysis as a useful quantitative tool for assessment of cardiac health in zebrafish and underscore the importance of nkx2.5 in maintaining normal heart rate and HRV during early conduction system development.

2014 ◽  
Vol 24 (2) ◽  
pp. 206-214 ◽  
Author(s):  
Wisse P. van der Meijden ◽  
Rolf Fronczek ◽  
Robert H. A. M. Reijntjes ◽  
Eleonora P. M. Corssmit ◽  
Nienke R. Biermasz ◽  
...  

2013 ◽  
Vol 14 ◽  
pp. e205
Author(s):  
W. Van Der Meijden ◽  
R. Fronczek ◽  
R. Reijntjes ◽  
G. Lammers ◽  
G. Van Dijk ◽  
...  

Author(s):  
T. Smuc ◽  
I. Maric ◽  
G. Bosanac ◽  
D. Gamberger ◽  
N. Bogunovic ◽  
...  

Med Phoenix ◽  
2017 ◽  
Vol 2 (1) ◽  
pp. 34-37
Author(s):  
Akhilesh Kumar Jha ◽  
Bikranta Rimal ◽  
Tarannum Khatun

Background: Ultrasonography is the reliable and safe way for the evaluation of pregnancy. Heart rate can be detected more confidently from the Ultrasonography. Heart rate is an important parameter for the evaluation of early pregnancy. The purpose of this study was to evaluate the normal heart rate in embryos/fetuses between 6 and 8 weeks of gestation.Method: In our region people are poor and most of them do not know the benefit of regular follow up examination during pregnancy. So most of pregnant women come to our centre at late stage of pregnancy. The number of pregnancy cases is good in our centre but the number of early pregnancy cases coming to regular follow up examination is low. Thus the study was conducted in 51 normal singleton pregnancies undergoing routine ultrasound examination during the first trimester of pregnancy. The duration of study was 6 weeks.Result: Out of 51 singleton pregnancies, 20 cases (39.2%) heart rate were between 131-150 beat per minute and 25 cases (49.0 %) heart rate were between 151-170 beat per minute. However 4 cases (7.8%) were between 110-120 beat per minute and 2 cases (3.9%) were more than 171 beat per minute. There were zero cases above the 180 beat per minute.Conclusion: The result of this study will help to evaluate abnormal and normal fetal heart rate so that early clinical decision whether to continue the pregnancy or terminate it can be taken, as Ultrasonography is only the method used in screening fetal well being in most of the region of our country.Med Phoenix Vol.2(1) July 2017, 34-37


2021 ◽  
Vol 8 (5) ◽  
pp. 48
Author(s):  
Drew Nassal ◽  
Jane Yu ◽  
Dennison Min ◽  
Cemantha Lane ◽  
Rebecca Shaheen ◽  
...  

The cardiac conduction system is an extended network of excitable tissue tasked with generation and propagation of electrical impulses to signal coordinated contraction of the heart. The fidelity of this system depends on the proper spatio-temporal regulation of ion channels in myocytes throughout the conduction system. Importantly, inherited or acquired defects in a wide class of ion channels has been linked to dysfunction at various stages of the conduction system resulting in life-threatening cardiac arrhythmia. There is growing appreciation of the role that adapter and cytoskeletal proteins play in organizing ion channel macromolecular complexes critical for proper function of the cardiac conduction system. In particular, members of the ankyrin and spectrin families have emerged as important nodes for normal expression and regulation of ion channels in myocytes throughout the conduction system. Human variants impacting ankyrin/spectrin function give rise to a broad constellation of cardiac arrhythmias. Furthermore, chronic neurohumoral and biomechanical stress promotes ankyrin/spectrin loss of function that likely contributes to conduction disturbances in the setting of acquired cardiac disease. Collectively, this review seeks to bring attention to the significance of these cytoskeletal players and emphasize the potential therapeutic role they represent in a myriad of cardiac disease states.


2007 ◽  
Vol 292 (1) ◽  
pp. H399-H407 ◽  
Author(s):  
Zhu-Shan Zhang ◽  
Joseph Tranquillo ◽  
Valentina Neplioueva ◽  
Nenad Bursac ◽  
Augustus O. Grant

Some mutations of the sodium channel gene NaV1.5 are multifunctional, causing combinations of LQTS, Brugada syndrome and progressive cardiac conduction system disease (PCCD). The combination of Brugada syndrome and PCCD is uncommon, although they both result from a reduction in the sodium current. We hypothesize that slow conduction is sufficient to cause S-T segment elevation and undertook a combined experimental and theoretical study to determine whether conduction slowing alone can produce the Brugada phenotype. Deletion of lysine 1479 in one of two positively charged clusters in the III/IV inter-domain linker causes both syndromes. We have examined the functional effects of this mutation using heterologous expression of the wild-type and mutant sodium channel in HEK-293-EBNA cells. We show that ΔK1479 shifts the potential of half-activation, V1/2m, to more positive potentials ( V1/2m = −36.8 ± 0.8 and −24.5 ± 1.3 mV for the wild-type and ΔK1479 mutant respectively, n = 11, 10). The depolarizing shift increases the extent of depolarization required for activation. The potential of half-inactivation, V1/2h, is also shifted to more positive potentials ( V1/2h = −85 ± 1.1 and −79.4 ± 1.2 mV for wild-type and ΔK1479 mutant respectively), increasing the fraction of channels available for activation. These shifts are quantitatively the same as a mutation that produces PCCD only, G514C. We incorporated experimentally derived parameters into a model of the cardiac action potential and its propagation in a one dimensional cable (simulating endo-, mid-myocardial and epicardial regions). The simulations show that action potential and ECG changes consistent with Brugada syndrome may result from conduction slowing alone; marked repolarization heterogeneity is not required. The findings also suggest how Brugada syndrome and PCCD which both result from loss of sodium channel function are sometimes present alone and at other times in combination.


2019 ◽  
Vol 116 (3) ◽  
pp. 605-618 ◽  
Author(s):  
Beth A Firulli ◽  
Rajani M George ◽  
Jade Harkin ◽  
Kevin P Toolan ◽  
Hongyu Gao ◽  
...  

Abstract Aims To examine the role of the basic Helix-loop-Helix (bHLH) transcription factor HAND1 in embryonic and adult myocardium. Methods and results Hand1 is expressed within the cardiomyocytes of the left ventricle (LV) and myocardial cuff between embryonic days (E) 9.5–13.5. Hand gene dosage plays an important role in ventricular morphology and the contribution of Hand1 to congenital heart defects requires further interrogation. Conditional ablation of Hand1 was carried out using either Nkx2.5 knockin Cre (Nkx2.5Cre) or α-myosin heavy chain Cre (αMhc-Cre) driver. Interrogation of transcriptome data via ingenuity pathway analysis reveals several gene regulatory pathways disrupted including translation and cardiac hypertrophy-related pathways. Embryo and adult hearts were subjected to histological, functional, and molecular analyses. Myocardial deletion of Hand1 results in morphological defects that include cardiac conduction system defects, survivable interventricular septal defects, and abnormal LV papillary muscles (PMs). Resulting Hand1 conditional mutants are born at Mendelian frequencies; but the morphological alterations acquired during cardiac development result in, the mice developing diastolic heart failure. Conclusion Collectively, these data reveal that HAND1 contributes to the morphogenic patterning and maturation of cardiomyocytes during embryogenesis and although survivable, indicates a role for Hand1 within the developing conduction system and PM development.


2020 ◽  
pp. 1-3
Author(s):  
Aslak Widerøe Kristoffersen ◽  
Per Kristian Knudsen ◽  
Thomas Møller

Abstract A four- and a half-month-old girl with severe dilated cardiomyopathy due to neonatal enterovirus myocarditis, treated with diuretics and milrinone for the past 4 months, was infected with SARS-CoV-2. The disease course was characterised by high fever and gastrointestinal symptoms. Cardiac function, as measured by echocardiography, remained stable. The treatment focused on maintaining a normal heart rate and a stable fluid balance. In children with severe underlying cardiac disease, even a mild SARS-CoV-2 infection can require close monitoring and compound treatment.


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