Frobert Aurélien, Valentin Jérémy, Magnin Jean-Luc, Riedo Erwin, Cook Stéphane, Giraud Marie-Noëlle
Cardiology, Department of Medicine, University and Hospital of Fribourg Fribourg, Switzerland.
Central Laboratory, Hospital Fribourg Fribourg, Switzerland.
Front Physiol. 2015 Nov 27;6:353. doi: 10.3389/fphys.2015.00353. eCollection 2015.
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.
In the present study, we investigated the prognostic value of cTnI for early estimation of the infarct size.
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.
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.
在小鼠和大鼠中进行冠状动脉结扎以诱导心肌梗死(MI)在临床前研究中被广泛应用。然而,心肌缺血损伤及随后的梗死面积高度可变。该模型缺乏标准化损害了有效转化至临床的可能性。心肌肌钙蛋白I(cTnI)是一种主要的临床相关生物标志物。
在本研究中,我们调查了cTnI对梗死面积早期估计的预后价值。
通过随机在冠状动脉的某个部位进行结扎,在小鼠和大鼠中诱导出不同大小的梗死灶。测量血浆cTnI水平的动力学变化。通过超声心动图评估心脏功能,从组织学切片评估梗死左心室的百分比和梗死扩展指数。我们观察到梗死大鼠的血浆cTnI水平在24小时达到峰值,而小鼠则在24至48小时达到峰值。假手术动物的cTnI水平低于15 ng/mL。结扎后4周评估的梗死扩展指数(EI)在大鼠和小鼠中分别显示出63%和71%的较大变异系数。我们显示cTnI水平与EI之间存在显著相关性,证明了其在小动物模型中对心肌损伤的预测价值。
我们证明了cTnI血浆水平作为主要早期标志物对于在实验动物模型中优化和有效管理心肌梗死的重要性。所呈现的结果强调在动物模型和临床试验中需要可比的生物标志物以改善转化。