Abstract

ObjectiveAnimal models are important to study basic mechanism of ischemic heart failure (HF). The objective of the study was to create rabbit models of myocardial infarction to investigate the structure‐function remodeling of the left ventricle (LV) and coronary arterial trees and the therapeutic effects of Tongxinluo Capsule.MethodNew Zealand white rabbits were randomly divided into sham group, model group and therapeutic group. The rabbit models were created through multiple coronary artery ligations. Echocardiographic, Micro‐CT and histological measurements were performed at postoperative 6 weeks and postoperative 12 weeks, respectively.ResultEchocardiographic measurements of the model group showed an approximately monotonic slope of ejection fraction and fractional shortening from 73% and 40% to 58% and 28% as well as persistent enlargement of LV cavity and slight mitral regurgitation at postoperative 12 weeks. Measurements of micro‐CT and histology revealed that coronary vascular sparseness and cardiac fibrosis related to inflammation occurred concurrently in adjacent zone of MI at postoperative 12 weeks although there was compensatory vascular growth at postoperative 6 weeks. Compared with the model group, the therapeutic group presented significant improvements in ejection fraction, fractional shortening, LV end‐systolic dimension and volume of cardiac output. The number of capillary vessels increased distinctly, while the infarct area decreased correspondingly.ConclusionsIn conclusion, these findings validate the proposed rabbit model and prove that the interaction of the degenerated coronary vasculature and increased ventricle wall stress relevant to cardiac fibrosis in vicinity of myocardial infarction (MI) facilitates the occurrence and development of ischemic HF. Furthermore, Tongxinluo Capsule has been proved in our study to play an essential role in protecting myocardium, improving blood supply of myocardium and relieving myocardial injury. To summarize, the post‐MI rabbit model can serve as a reference to test various drugs for treatment of ischemic HF, and contributes to the clinical application of Tongxinluo Capsule in the future.Support or Funding InformationThis research is supported in part by the National Natural Science Foundation of China Grant 11372010, 11672006 (Y Huo); Shenzhen Science and Technology Innovation Institution (China) Grant JCYJ20160427170536358 (Y Huo); and Hebei University (China) Grant 2015A1002 (Y Huo).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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