Progressive left ventricular remodeling and apoptosis late after myocardial infarction in mouse heart

We tested the hypothesis that left ventricular (LV) remodeling late after m yocardial infarction (MI) is associated with myocyte apoptosis in myocardiu m remote from the infarcted area and is related temporally to LV dilation a nd contractile dysfunction. One, four, and six months after MI caused by co ronary artery ligation, LV volume and contractile function were determined using an isovolumic balloon-in-LV Langendorff technique. Apoptosis and nucl ear morphology were determined by terminal deoxynucleotidyl transferase-med iated nick end-labeling (TUNEL) and Hoechst 33258 staining. Progressive LV dilation 1-6 mo post-MI was associated with reduced peak LV developed press ure (LVDP). In myocardium remote from the infarct, there was increased wall thickness and expression of atrial natriuretic peptide mRNA consistent wit h reactive hypertrophy. There was a progressive increase in the number of T UNEL-positive myocytes from 1 to 6 mo post-MI (2.9-fold increase at 6 mo; P < 0.001 vs. sham). Thus LV remodeling late post-MI is associated with incre ased apoptosis in myocardium remote from the area of ischemic injury. The f requency of apoptosis is related to the severity of LV dysfunction.