Infarct size and post-infarct inflammation determine the risk of cardiac rupture in mice

Background/objectivesInfarct size (IS) is a determinant of pathophysiological events after myocardial infarction (MI), but its relation to the risk of cardiac rupture remains undefined.MethodsMI was induced in 129sv and C57Bl/6 mice. Left ventricular (LV) remodelling was examined by echocardiography prior to the onset of rupture. Changes in muscle tensile strength and expression of inflammatory factors were determined. Autopsy was performed and IS measured.ResultsRupture incidence was higher in 129sv than C57Bl/6 mice (62% vs. 33%, P < 0.001). Rupture occurred in mice with IS over a threshold, which was smaller in 129sv than C57Bl/6 mice (20% vs. 30%). 129sv mice with IS > 30% had a higher incidence of rupture than those with IS 20–30%. Echocardiography revealed IS-dependent LV remodelling and dysfunction and 129sv mice had a better-preserved function compared with C57Bl/6 counterparts. 129sv but not C57Bl/6 mice that subsequently developed rupture showed more severe regional dysfunction and remodelling compared with IS-matched non-ruptured hearts. Tensile strength of the infarcted myocardium was reduced significantly, which was IS-related. 129sv mice had higher expression levels of inflammatory mediators in the infarcted myocardium or circulating inflammatory cells, underlying the higher risk of rupture in this strain than C57Bl/6.ConclusionsA critical IS level is necessary for post-MI rupture and IS correlates with the reduction in muscle tensile strength. Strain differences exist in global function and regional or systemic inflammation that explain the different risk of rupture or heart failure between strains. Limiting IS or minimizing inflammation would lower the risk of ventricular rupture.