Abstract
Coronary artery ligations to induce myocardial infarction (MI) in mice and rats are widely used in preclinical investigation. However, myocardial ischemic damage and subsequent infarct size are highly variable. The lack of standardization of the model impairs the probability of effective translation to the clinic. Cardiac Troponin I (cTnI) is a major clinically relevant biomarker.Aim: In the present study, we investigated the prognostic value of cTnI for early estimation of the infarct size.Methods and Results: Infarcts of different sizes were induced in mice and rats by ligation, at a random site, of the coronary artery. Kinetics of the plasma levels of cTnI were measured. Heart function was evaluated by echocardiography, the percentage of infarcted left ventricle and infarct expansion index were assessed from histological section. We observed that plasma cTnI level peaked at 24 h in the infarcted rats and between 24 and 48 h in mice. Sham operated animals had a level of cTnI below 15 ng/mL. Infarct expansion index (EI) assessed 4 weeks after ligation showed a large variation coefficient of 63 and 71% in rats and mice respectively. We showed a significative correlation between cTnI level and the EI demonstrating its predictive value for myocardial injury in small animal models.Conclusion: we demonstrated the importance of cTnI plasma level as a major early marker to assist in the optimal and efficient management of MI in laboratory animals model. The presented results stress the need for comparable biomarkers in the animal model and clinical trials for improved translation.
Highlights
Heart disease remains a major cause of mortality worldwide
The myocardial infarction (MI) group consisted of 22 rats and 16 mice that underwent a left anterior descending coronary artery (LAD) ligation
The LAD ligations resulted in a reduction in heart function, and there was a significant difference between the LAD-ligated groups and the healthy and sham groups
Summary
Heart disease remains a major cause of mortality worldwide. New treatment strategies using gene and cell therapies have gained interest because their efficacy has been established in a preclinical setting. Numerous phase 1 clinical trials have demonstrated cTnI in Infarcted Small Animals the safety and feasibility of new therapies that rely on the delivery of cells to the myocardium, the efficacy of the treatments have not been as convincing or effective as suggested in the preclinical studies. The reasons for these shortcomings are multifactorial, and general recommendations have been proposed to improve translational research in heart failure (Patten and Hall-Porter, 2009). The scientific community believes that the optimization of preclinical studies in small animal models is of utmost importance for developing safe and effective therapies and increasing the probability of effective translation to the clinic (Houser et al, 2012)
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