Francisco Amanda Fortes, Sousa Giovane R, Vaughan Mhairi, Langston Harry, Khan Archie, Jayawardhana Shiromani, Taylor Martin C, Lewis Michael D, Kelly John M
Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
Harvard Medical School, Section on Immunobiology, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA.
Pathogens. 2023 Nov 17;12(11):1364. doi: 10.3390/pathogens12111364.
Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite 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 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 utilised electrocardiography (ECG) to monitor -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 remodelling and for examining the potential of antiparasitic drugs to prevent or alleviate CCC development and progression.
慢性查加斯心肌病(CCC)由原生动物寄生虫感染引起,是流行国家心脏病的常见病因。我们之前发现,长期感染JR株的C3H/HeN小鼠的心脏纤维化差异很大,反映了人类心脏病的范围。在本研究中,我们检查了这种宿主-寄生虫组合中的心脏功能异常,以确定其作为CCC实验模型的潜力。我们利用心电图(ECG)监测感染小鼠,并确定心电图指标是否与心脏功能异常相关。我们发现,C3H/HeN:JR组合在急性期经常出现早期发作的CCC指标,如窦性心动过缓和右束支传导阻滞,以及PQ、PR、RR、ST和QT间期延长。我们的模型在急性期表现出高水平的心脏炎症和增强的诱导型一氧化氮合酶(iNOS)表达,但去神经支配似乎在病理过程中不起作用。这些结果证明了C3H/HeN:JR宿主-寄生虫组合作为CCC模型的潜力,可用于筛选针对心脏重塑的新化合物,以及研究抗寄生虫药物预防或减轻CCC发展和进展的潜力。