Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats

Abstract

We investigated the role of cardiomyocyte apoptosis in the remodeling of the left ventricle from 24 h to 12 wk after myocardial infarction in the rat. Infarct size planimetry, quantification of cardiomyocyte apoptosis, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) methodology, and echocardiography (left ventricular diastolic diameter and ejection fraction) were performed. Sham-operated animals showed low rates of cardiomyocyte apoptosis (0.03%) and no change in diastolic diameter or ejection fraction during the study. Twenty-four hours after infarction, TUNEL positivity was high in the infarct areas (1.4%) and border zones (4.9%). It declined to 0.34% (P < 0.01 vs. sham) at 4 wk and 0.10% at 12 wk in the border zones. In the remote myocardium, cardiomyocyte apoptosis increased to 0.07% (P = 0.03 vs. sham) on day 1 and remained on the same level up to 4 wk. The increase in diastolic diameter 1-4 wk after infarction correlated (r = 0.60, P < 0.01) with cardiomyocyte apoptosis in the noninfarcted myocardium, which quantitatively contributed most (>50%) to the apoptotic cell loss by 4 wk.

The neuroprotective agent Rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction

“…More specifically, RG significantly preserved LVEDD and LVESD increased almost from 7 days post‐MI in our study. This observation provides a possible association towards apoptosis in the RR which has previously been associated with post‐infarction LVR, cardiac dilation, and increased cardiac fibrosis after MI, respectively 37. In addition, we also observed a shift of the Bcl2/Bax ratio toward the regulator protein Bcl2 in the RR (although not statistically significant).…”

“…It has been shown that in contrast to the BZ, the amount of apoptosis in the RR is correlated with an increase in the ventricular diameter 4 weeks after infarction 37. More specifically, RG significantly preserved LVEDD and LVESD increased almost from 7 days post‐MI in our study.…”

Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes

“…Four weeks after the STZ or citrate buffer injections the animals underwent either sham or MI operation (n=7-11 in each group). MI was produced by ligation of the left anterior descending coronary artery as described [3]. The rats were killed 1, 4 and 12 weeks after the operation, the hearts were weighed, embedded in paraffin, and cut into sections for histology, planimetry, and assessment of apoptosis and connective tissue growth factor (CTGF).…”

“…The presence of signs of acute MI (eosinophilia, karyolysis, and leucocyte infiltration) or collagen scars compatible with MI was verified by examination of Van Gieson stained transverse left ventricular (LV) sections. Infarct size was determined planimetrically [3].…”

“…We and others have shown that cardiomyocyte apoptosis remains increased several months post-MI, correlating with ventricular enlargement [3,4]. As recent studies have shown that diabetes could be associated with enhanced susceptibility to apoptosis [5], we wanted to study in an experimental rat MI model, whether cardiomyocyte apoptosis is increased in diaDiabetic patients have about a two-fold increase in a risk of short-and long-term mortality after myocardial infarction (MI).…”