Mouse models of myocardial infarction: comparing permanent ligation and ischaemia-reperfusion

Abstract

Myocardial infarction (MI) is a disease of major consequence in the modern world, causing permanent, irreversible damage to the heart. Survivors are at risk for developing further cardiovascular pathologies such as heart failure. Further study of MI injury is crucial to improve the understanding and treatment of the post-MI heart. The most commonly used model for MI in vivo is surgical ligation of the left anterior descending coronary artery (LAD). There are two predominant approaches: permanent ligation (PL), where the LAD is permanently occluded with a suture, or ischaemia-reperfusion (IR), where the LAD is temporarily occluded before removing the suture to restore blood flow and tissue reperfusion. PL results in the majority of the area at risk becoming infarcted, leading to significant apoptotic cell death and a large scar. Conversely, IR salvages some of the area at risk; thus, the scar is smaller and includes reperfusion injury, an additional, albeit smaller, second wave of necrotic damage. PL may be a more appropriate model choice for studies of heart tissue injury and wound healing, owing to the larger, more consistent infarcts, while IR enables the study of reperfusion injury. Both are clinically relevant, and the choice of model depends upon the precise pre-clinical research questions to be addressed.

Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment

“…In permanent occlusion models, the lack of blood-flow to the infarct and limited flow to the BZ limits infiltration and myocyte recovery. As such, larger infarcts are more observed in permanent occlusion compared to reperfusion [126]. Post-MI time-course in small-animal models, pre-clinical large-animal models and human MI are different as well [127].…”

“…In the last 20 years, mice have taken centre stage as animal model, mostly due to the power of genetic manipulation [126]. MI has mostly been induced by coronary artery ligation and mice are able to survive large infarcts of up to 40% of the LV.…”

Senescence and senolytics in cardiovascular disease: Promise and potential pitfalls

“…Indeed, it has been previously demonstrated that following acute non-ischaemic myocardial damage, with a single high dose of isoproterenol, the murine heart has a robust cardiac regenerative potential with functional recovery occurring in as little as 28 days ( Ellison et al, 2007 ; Ellison et al, 2013 ). In contrast to the LAD-Ligation model of MI, which results in a severe and segmental loss of approximately 20–30 % of LV CMs ( De Villiers and Riley, 2020 ), high dose isoproterenol causes diffuse tissue damage that more recapitulates normal muscle wear-and-tear and death in only 8–10 % of apical LV CMs ( Ellison et al, 2007 , 2013 ). Therefore, with a diffuse CM death in the absence of an ischaemic insult and with the presence of a patent blood supply, CM regeneration may be sufficient to maintain tissue integrity and function, explaining the observed cardio-beneficial effects of senotherapies in aged mice ( Anderson et al, 2019 ; Lewis-McDougall et al, 2019 ; Walaszczyk et al, 2019 ).…”

Cognitive impairment in myocardial infarction and heart failure

“…For permanent LAD ligation model, it is directly applicable to the approximate 30% of MI patients who do not receive reperfusion therapy or also receive, but progress to heart failure. 90 This model may be a more appropriate model choice for studies of heart tissue injury and wound healing, owing to the larger, more consistent infarcts. The decreasing LVEF after LAD ligation was associated with the reduction of CBFinduced cognitive impairment and dendritic spine loss.…”