Noninvasive Electrocardiography in the Perinatal Mouse

Summary

Here, we present a noninvasive electrocardiography (ECG) protocol, optimized for early postnatal mice, that does not require the use of anesthetics.

Abstract

Electrocardiography (ECG) has long been relied upon as an effective and reliable method of assessing cardiovascular (and cardiopulmonary) function in both human and animal models of disease. Individual heart rate, rhythm, and regularity, combined with quantitative parameters collected from ECG, serve to assess the integrity of the cardiac conduction system as well as the integrated physiology of the cardiac cycle. This article provides a comprehensive description of the methods and techniques used to perform a noninvasive ECG on perinatal and neonatal mouse pups as early as the first postnatal day, without requiring the use of anesthetics. This protocol was designed to directly address a need for a standardized and repeatable method for obtaining ECG in newborn mice. From a translational perspective, this protocol proves to be entirely effective for characterization of congenital cardiopulmonary defects generated using transgenic mouse lines, and particularly for analysis of defects causing lethality at or during the first postnatal days. This protocol also aims to directly address a gap in the scientific literature to characterize and provide normative data associated with maturation of the early postnatal cardiac conduction system. This method is not limited to a specific postnatal timepoint, but rather allows for ECG data collection in neonatal mouse pups from birth to postnatal day 10 (P10), a window that is of critical importance for modeling human diseases in vivo, with particular emphasis on congenital heart disease (CHD).

Introduction

Cardiac function can be measured in different ways, the most common of which includes the use of electrocardiography (ECG) to analyze the conduction of electric current through the heart as well as its overall cardiac cycle and function¹. Electrocardiography continues to be a useful diagnostic tool for identifying and characterizing cardiac anomalies in both human and animal models of disease^1,2. Irregularities in an electrocardiogram reading can be found in abnormal cardiac development (i.e., congenital heart disease (CHD)), and can include arrhythmias manifesting as changes in heart r

Protocol

The following protocol follows the standards of the Institutional Animal Care and Use Committee of the University of New England. Close observation of the protocol should deliver satisfactory ECG reads in all examined neonates (n > 70).

1. Device preparations

1. Plug the device into the USB port of a computer with the ECG software downloaded on it. The measuring device will automatically begin heating up to (37 °C/98.6 °F). The internal heating unit is contained within the measuring unit and heats only the plastic surface. The silver wire electrodes are not heated.
2. Allow approximately 15 min for the surface

Results

An ideal ECG would have a clear, prominent signal that allows all waves to be analyzed in several different time frames (Figure 1). The laboratory initially employed a custom application of an electromyography apparatus to produce ECGs of an unsatisfactory quality, which only allowed us to analyze basic parameters such as heart rate (Figure S1). This inspired work with a company to develop a novel prototype ECG device specifically for the analysis of early postnatal mouse pu...

Discussion

The data points collected in perinatal day 1 mouse pups are slightly below the average expected values for adult mice (500-700 beats per minute).⁸ There is an increase in heart rate as the mouse ages, which falls more in line for the expected values (Table 1). However, it is important to emphasize that neonatal values were on the lower end of this range, supporting the idea that normative values should be documented in an age-specific manner. This method is different than other el...

Materials

Name	Company	Catalog Number	Comments
LabScribe4	iWorx	LabScribe4	Software used to record ECG	https://www.iworx.com/users/teaching.php
Neonatal Mouse ECG & Respiration System	iWorx	RS-NMECG : Neonatal Mouse ECG	ECG device	https://www.iworx.com/research/cardiac-function/rs-nmecg/
Tensive Conductive Adhesive Gel	Parker Laboratories, Inc	22-60	Tac-gel used as conductive gel for ECG	https://www.parkerlabs.com/tensive.asp