Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease

Amanda Fortes Francisco
* ORCID logo ,
Giovane R. Sousa
,
Mhairi Vaughan
,
Harry Langston
,
Archie Khan
,
Shiromani Jayawardhana
,
Martin C. Taylor
ORCID logo ,
Michael D. Lewis
ORCID logo ,
John M. Kelly
Version 1 : Received: 14 October 2023 / Approved: 16 October 2023 / Online: 16 October 2023 (12:36:35 CEST)

A peer-reviewed article of this Preprint also exists.

Francisco, A.F.; Sousa, G.R.; Vaughan, M.; Langston, H.; Khan, A.; Jayawardhana, S.; Taylor, M.C.; Lewis, M.D.; Kelly, J.M. Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease. Pathogens 2023, 12, 1364. Francisco, A.F.; Sousa, G.R.; Vaughan, M.; Langston, H.; Khan, A.; Jayawardhana, S.; Taylor, M.C.; Lewis, M.D.; Kelly, J.M. Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease. Pathogens 2023, 12, 1364.

Abstract

Chronic Chagas Cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilized electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodeling and for examining the potential of anti-parasitic drugs to prevent or alleviate CCC development and progression.

Keywords

Trypanosoma cruzi; electrocardiography (ECG); Chronic Chagas Cardiomyopathy; Chagas heart disease

Subject

Biology and Life Sciences, Parasitology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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