Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals

The analysis of beating rate provides information on the modulatory action of the autonomic nervous system on the heart, which mediates adjustments of cardiac function to meet hemodynamic requirements. In patients with myocardial infarction, alterations of heart rate variability (HRV) have been corr...

Full description

Bibliographic Details
Main Authors: Emanuele Pizzo, Silvia Berrettoni, Ridhima Kaul, Daniel O. Cervantes, Valeria Di Stefano, Sudhir Jain, Jason T. Jacobson, Marcello Rota
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2022.843144/full
_version_ 1811302494592040960
author Emanuele Pizzo
Silvia Berrettoni
Ridhima Kaul
Daniel O. Cervantes
Valeria Di Stefano
Sudhir Jain
Jason T. Jacobson
Jason T. Jacobson
Marcello Rota
author_facet Emanuele Pizzo
Silvia Berrettoni
Ridhima Kaul
Daniel O. Cervantes
Valeria Di Stefano
Sudhir Jain
Jason T. Jacobson
Jason T. Jacobson
Marcello Rota
author_sort Emanuele Pizzo
collection DOAJ
description The analysis of beating rate provides information on the modulatory action of the autonomic nervous system on the heart, which mediates adjustments of cardiac function to meet hemodynamic requirements. In patients with myocardial infarction, alterations of heart rate variability (HRV) have been correlated to the occurrence of arrhythmic events and all-cause mortality. In the current study, we tested whether experimental rodent models of myocardial infarction recapitulate dynamics of heart rate variability observed in humans, and constitute valid platforms for understanding mechanisms linking autonomic function to the development and manifestation of cardiovascular conditions. For this purpose, HRV was evaluated in two engineered mouse lines using electrocardiograms collected in the conscious, restrained state, using a tunnel device. Measurements were obtained in naïve mice and animals at 3–∼28 days following myocardial infarction, induced by permanent coronary artery ligation. Two mouse lines with inbred and hybrid genetic background and, respectively, homozygous (Homo) and heterozygous (Het) for the MerCreMer transgene, were employed. In the naïve state, Het female and male mice presented prolonged RR interval duration (∼9%) and a ∼4-fold increased short- and long-term RR interval variability, with respect to sex-matched Homo mice. These differences were abrogated by pharmacological interventions inhibiting the sympathetic and parasympathetic axes. At 3–∼14 days after myocardial infarction, RR interval duration increased in Homo mice, but was not affected in Het animals. In contrast, Homo mice had minor modifications in HRV parameters, whereas substantial (> 50%) reduction of short- and long-term RR interval variation occurred in Het mice. Interestingly, ex vivo studies in isolated organs documented that intrinsic RR interval duration increased in infarcted vs. non-infarcted Homo and Het hearts, whereas RR interval variation was not affected. In conclusion, our study documents that, as observed in humans, myocardial infarction in rodents is associated with alterations in heart rhythm dynamics consistent with sympathoexcitation and parasympathetic withdrawal. Moreover, we report that mouse strain is an important variable when evaluating autonomic function via the analysis of HRV.
first_indexed 2024-04-13T07:29:05Z
format Article
id doaj.art-44fe757a6c204c239d91091179d281e2
institution Directory Open Access Journal
issn 2297-055X
language English
last_indexed 2024-04-13T07:29:05Z
publishDate 2022-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cardiovascular Medicine
spelling doaj.art-44fe757a6c204c239d91091179d281e22022-12-22T02:56:24ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-05-01910.3389/fcvm.2022.843144843144Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental AnimalsEmanuele Pizzo0Silvia Berrettoni1Ridhima Kaul2Daniel O. Cervantes3Valeria Di Stefano4Sudhir Jain5Jason T. Jacobson6Jason T. Jacobson7Marcello Rota8Department of Physiology, New York Medical College, Valhalla, NY, United StatesDepartment of Physiology, New York Medical College, Valhalla, NY, United StatesDepartment of Physiology, New York Medical College, Valhalla, NY, United StatesDepartment of Physiology, New York Medical College, Valhalla, NY, United StatesDepartment of Physiology, New York Medical College, Valhalla, NY, United StatesDepartment of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United StatesDepartment of Physiology, New York Medical College, Valhalla, NY, United StatesDepartment of Cardiology, Westchester Medical Center, Valhalla, NY, United StatesDepartment of Physiology, New York Medical College, Valhalla, NY, United StatesThe analysis of beating rate provides information on the modulatory action of the autonomic nervous system on the heart, which mediates adjustments of cardiac function to meet hemodynamic requirements. In patients with myocardial infarction, alterations of heart rate variability (HRV) have been correlated to the occurrence of arrhythmic events and all-cause mortality. In the current study, we tested whether experimental rodent models of myocardial infarction recapitulate dynamics of heart rate variability observed in humans, and constitute valid platforms for understanding mechanisms linking autonomic function to the development and manifestation of cardiovascular conditions. For this purpose, HRV was evaluated in two engineered mouse lines using electrocardiograms collected in the conscious, restrained state, using a tunnel device. Measurements were obtained in naïve mice and animals at 3–∼28 days following myocardial infarction, induced by permanent coronary artery ligation. Two mouse lines with inbred and hybrid genetic background and, respectively, homozygous (Homo) and heterozygous (Het) for the MerCreMer transgene, were employed. In the naïve state, Het female and male mice presented prolonged RR interval duration (∼9%) and a ∼4-fold increased short- and long-term RR interval variability, with respect to sex-matched Homo mice. These differences were abrogated by pharmacological interventions inhibiting the sympathetic and parasympathetic axes. At 3–∼14 days after myocardial infarction, RR interval duration increased in Homo mice, but was not affected in Het animals. In contrast, Homo mice had minor modifications in HRV parameters, whereas substantial (> 50%) reduction of short- and long-term RR interval variation occurred in Het mice. Interestingly, ex vivo studies in isolated organs documented that intrinsic RR interval duration increased in infarcted vs. non-infarcted Homo and Het hearts, whereas RR interval variation was not affected. In conclusion, our study documents that, as observed in humans, myocardial infarction in rodents is associated with alterations in heart rhythm dynamics consistent with sympathoexcitation and parasympathetic withdrawal. Moreover, we report that mouse strain is an important variable when evaluating autonomic function via the analysis of HRV.https://www.frontiersin.org/articles/10.3389/fcvm.2022.843144/fullheart rate variability (HRV)myocardial infarctionautonomic regulation of heartmouseelectrocardiogram
spellingShingle Emanuele Pizzo
Silvia Berrettoni
Ridhima Kaul
Daniel O. Cervantes
Valeria Di Stefano
Sudhir Jain
Jason T. Jacobson
Jason T. Jacobson
Marcello Rota
Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals
Frontiers in Cardiovascular Medicine
heart rate variability (HRV)
myocardial infarction
autonomic regulation of heart
mouse
electrocardiogram
title Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals
title_full Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals
title_fullStr Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals
title_full_unstemmed Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals
title_short Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals
title_sort heart rate variability reveals altered autonomic regulation in response to myocardial infarction in experimental animals
topic heart rate variability (HRV)
myocardial infarction
autonomic regulation of heart
mouse
electrocardiogram
url https://www.frontiersin.org/articles/10.3389/fcvm.2022.843144/full
work_keys_str_mv AT emanuelepizzo heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT silviaberrettoni heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT ridhimakaul heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT danielocervantes heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT valeriadistefano heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT sudhirjain heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT jasontjacobson heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT jasontjacobson heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals
AT marcellorota heartratevariabilityrevealsalteredautonomicregulationinresponsetomyocardialinfarctioninexperimentalanimals