Noninvasive assessment of autonomic modulation of heart rate variability in the Ts65Dn mouse model of Down syndrome: A proof of principle study

Autor: Melissa R. Stasko, Mark W. Johnson, Adriano L. Roque, Talita Dias da Silva, Luiz Carlos de Abreu, Alberto C.S. Costa
Rok vydání: 2019
Předmět:
Agonist
Chronotropic
Male
Cardiovascular Conditions
Disorders and Treatments
medicine.medical_specialty
Carbachol
Physiology
medicine.drug_class
Genetic Conditions Disorders and Treatments
Down syndrome
Adrenergic
030204 cardiovascular system & hematology
Cholinergic Agonists
Autonomic Nervous System
Risk Assessment
Ts65Dn
lcsh:Physiology
Neurological Conditions
Disorders and Treatments
03 medical and health sciences
Electrocardiography
Mice
0302 clinical medicine
Heart Rate
Physiology (medical)
Internal medicine
Heart rate
medicine
Heart rate variability
Animals
Original Research
lcsh:QP1-981
business.industry
Isoproterenol
Heart
Adrenergic beta-Agonists
animal models
Mice
Inbred C57BL
Autonomic nervous system
Disease Models
Animal
Cardiology
cardiovascular system
Cholinergic
Female
business
030217 neurology & neurosurgery
medicine.drug
Zdroj: Physiological Reports
Physiological Reports, Vol 8, Iss 12, Pp n/a-n/a (2020)
ISSN: 2051-817X
Popis: Introduction The Ts65Dn mouse is the most widely used animal model of Down syndrome (DS). Differences in autonomic regulation of heart rate variability (HRV) in individuals with DS have been hypothesized. Pharmacological studies in animal models may help us understand mechanisms underlying observed changes in HRV in people with DS. Objective To investigate the use a new, noninvasive technique to assess cardiac autonomic modulation in Ts65Dn mice under the effect of adrenergic and cholinergic agonists. Method We recorded electrocardiograms (ECGs) from 12 Ts65Dn and 12 euploid control mice. A 30‐min baseline recording was followed by the injection of an adrenergic (isoproterenol [Iso]) or cholinergic (carbachol [CCh]) agonist. Heart rate and HRV were analyzed using a series of methods customized for mice. Results and Discussion The ECG apparatus described here allowed us to detect noninvasively long series of heartbeats in freely‐moving animals. During baseline conditions, the yield of detectable heartbeats was 3%–27% of the estimated total number of events, which increased to 35%–70% during the 15‐min period after either Iso or CCh injections. Ts65Dn mice displayed a robust enhanced Iso‐induced negative chronotropic rebound response compared with euploid control mice. We observed a significantly smaller CCh response in Ts65Dn versus control euploid mice in the 6‐ to 10‐min‐interval postcarbachol injection. Conclusion This work showed that the techniques described here are sufficient for this type of study. However, future studies involving the use of more selective pharmacological agents and/or genetic manipulations will be key to advance a mechanistic understanding of cardiac autonomic regulation in DS.
We used a new, noninvasive technique to assess cardiac autonomic modulation in the Ts65Dn mouse model of Down syndrome under the effect of adrenergic and cholinergic agonists. This new ECG recording apparatus has the potential to be very useful to investigators studying heart rate and heart rate variability in rodent models of human disorders. However, future studies involving the use of more selective pharmacological agents and/or genetic manipulations of the mouse models of DS will be necessary to complement this work.
Databáze: OpenAIRE
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