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Control of the heart rate of rat embryos during the organogenic period

Authors Ritchie HE, Ragnerstam C, Gustafsson E, Jonsson JM, Webster WS

Received 15 June 2016

Accepted for publication 26 August 2016

Published 8 November 2016 Volume 2016:4 Pages 147—159

DOI https://doi.org/10.2147/HP.S115050

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Dörthe Katschinski


Helen E Ritchie,1 Carolina Ragnerstam,2 Elin Gustafsson,2 Johanna M Jonsson,2 William S Webster2

1Discipline of Biomedical Science, Sydney Medical School, University of Sydney, Lidcombe, 2Department of Anatomy and Histology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia

Abstract: The aim of this study was to gain insight into whether the first trimester embryo could control its own heart rate (HR) in response to hypoxia. The gestational day 13 rat embryo is a good model for the human embryo at 5–6 weeks gestation, as the heart is comparable in development and, like the human embryo, has no functional autonomic nerve supply at this stage. Utilizing a whole-embryo culture technique, we examined the effects of different pharmacological agents on HR under normoxic (95% oxygen) and hypoxic (20% oxygen) conditions. Oxygen concentrations ≤60% caused a concentration-dependent decrease in HR from normal levels of ~210 bpm. An adenosine agonist, AMP-activated protein kinase (AMPK) activator and KATP channel opener all caused bradycardia in normoxic conditions; however, putative antagonists for these systems failed to prevent or ameliorate hypoxia-induced bradycardia. This suggests that the activation of one or more of these systems is not the primary cause of the observed hypoxia-induced bradycardia. Inhibition of oxidative phosphorylation also decreased HR in normoxic conditions, highlighting the importance of ATP levels. The β-blocker metoprolol caused a concentration-dependent reduction in HR supporting reports that β1-adrenergic receptors are present in the early rat embryonic heart. The cAMP inducer colforsin induced a positive chronotropic effect in both normoxic and hypoxic conditions. Overall, the embryonic HR at this stage of development is responsive to the level of oxygenation, probably as a consequence of its influence on ATP production.

Keywords:
embryonic heart rate, embryo, bradycardia, in vitro, ATP, hypoxia

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