GW24-e3624 Myocardial regeneration in acute myocardial infarction rat model

Objectives To investigate the myocardial proliferation/regeneration and myocardial cell apoptosis during different time points and in different parts of the heart in acute myocardial infarction (AMI) young and aged rat model. Methods young and aged Sprague-Dawley (SD) rats were respectively randomly divided into four groups, young and aged AMI groups and sham-operated groups. All animals underwent a left thoracotomy at the fourth intercostal space. A typical AMI model was created by ligaturing left anterior descending coronary. While in the sham-operated group, rats underwent the same process excepting coronary artery ligation. All the rats were sacrificed on day 1, 3, 5, 7, 10, 14, 30 and 60 respectively after the operation and ventricle tissues were harvested. 12 and 24 hours before sacrifice 5-Bromo-2-deoxyUridine (Brdu) (50 mg/kg) was injected intraperitoneally. Morphological and pathological changes of the myocardium were observed. Brdu-positive and c-kit and Brdu double-positive myocardial cells were calculated. The myocardial cell apoptosis indexes (AI) were tested by TUNEL, and proliferation cells were identified with α-sarcomeric actin antibody. Results In young rats, Brdu-positive myocardial cells were significantly increased in AMI rats 5 days after surgery. The Brdu-positive myocardial cells showed greatest increases and was 2.1 times that of the young group rats (1.26% ± 0.15% vs. 0.22 ± 0.06%, p < 0.05) on the 7th day. While in the right ventricle it was 2.4 times that of the young rats (0.75% ± 0.12% vs. 0.18% ± 0.07%, p < 0.05) on the 7th day. There was no significant difference between the two groups on 60th day. Around infarct border zone Brdu-positive cells were 1.7-fold more than that in the right ventricle (p <0.01) on the 7th day and was 1.4-fold (p <0.01) on the 14th day. In the aged rats, Brdu-positive myocardial cells significantly increased more than that of young rats both in infarct border zone and non infarct zone 5 days after surgery (p < 0.05). The Brdu-positive myocardial cells were markedly increased and was 2.1 times more than that in the young group rats (2.63% ± 0.12% vs. 1.26 ± 0.15%, p < 0.05) around infarct border zone on the 7th day. While in the right ventricle it was 2.4 times more than that of the young rats (1.82% ± 0.57% vs. 0.75% ± 0.12%, p < 0.05) on the 7th day. There was no significant difference between the two groups on the 30th day. AI in aged rats on the 1th day after infarction were 1.35 times (41.7% ± 1.6% vs. 30.9% ± 3.8%, p < 0.05) higher than that of the youth group. There was no significant difference between the two groups on the 30th day. Some of Neonatal cardiomyocytes were α-sarcomeric actin positive. The c-kit and Brdu double-positive myocardial cells were also observed. Mostly, these myocardial nuclear were small and round. Conclusions Our primary study indicated that The myocardial proliferation/regeneration increased significantly after AMI both in infarct and was time-dependent. New myocardial cells in aged rats after MI were more than that in young rats, and the AI was higher too. Neonatal cells had characteristics of myocardial cell. Some of the Brdu-positive cells also expressed c-kit and indicated that these new cells had some characteristics of cardiac stem cells.