Comparative Study Among Three Different Models for Induction of Acute Myocardial Infarction in Rats
Authors: Elshaer Ahmed , Sobhy Ahmed Elsaeed , Elalfy Mohammed Mohsen , Ghoneem Alyaa Mohammed , Elhawary Amira Kamal , Attia Mohammed Ahdy 
Published: October 2021

Abstract

Aim
Laboratory study of Acute Myocardial Infarction (AMI) has become of great importance for further investigations about prevention, diagnosis and treatment of the increasing number of patients worldwide. In this study, we are seeking the best experimental AMI model by comparing three methods by which AMI can be experimentally induced in rats to illuminate the most reliable model to use in further studies.

Methods and Results
Experimentally, AMI can be produced by either drug induced methods or surgical methods. Here, we compared two drug induced methods (isoproterenol and doxorubicin) and a surgical model to find out which method is best simulating human AMI.
50 male sprague dowley rats were put into 5 groups, each contained 10 rats as follows. Surgical group in which the proximal left anterior descending coronary artery (LADCA) was dissected and ligated. Isoproterenol group in which Isoproterenol (300 gm/kg) was injected in ten rats subcutaneously on 2 doses a day apart. Doxorubicin group in which doxorubicin (2.5 mg/kg) was given intraperitonially every other day for total cumulative dose of 15 mg/kg. Control group where rats received only 2 ml of saline intraperitonially or subcutaneously. Sham group where rats underwent a similar surgery, but without LADAC ligation.
After the induction, the biochemical parameter (serum Troponin I) at 12, 24, 36, 48 and 72 hours and histopathological changes (using hematoxylin, eosin and Mallory's trichrome stains) in all groups on days 1, 7, 14 and 21 were recorded. Data were statically analyzed, and Troponin curves were designed for each group to be correlated with that of AMI in human.
After 7 days, histopathological studies of the surgical group exhibited wide areas of focal fibrosis at the apex and scattered mononuclear inflammatory cells infiltration. While the isoproterenol group showed moderate degree of inflammation with multifocal areas of fibrosis and scattered mononuclear inflammatory cells. However, the doxorubicin group showed more or less normal histology of cardiomyocytes.
Biochemical studies reflected a significant difference in serum Troponin levels and peak timing among the groups. The surgical and isoproterenol groups Troponin peaked around 24 hours after the intervention, with higher levels in the surgical group. However, the doxorubicin group showed lower peaks around 36 hours post intervention.
Correlations with human AMI histopathology and biochemical markers show more mimicking changes in the surgical group when compared to the other models, followed by the isoproterenol group and least similar in the doxorubicin- induced group.
However, the survival rate of rats in the isoproterenol group was superior, followed by the surgical group and the doxorubicin group showed the lowest survival rates.

Conclusions
Surgical induction of AMI in rats achieves the high similarity to AMI in human but the low survival rates jeopardize the reliability of the model. However, isoproterenol shows sufficient levels of mimicking and higher survival indicating the highest reliability in simulation. Doxorubicin based models are the least reliable.