[Myocardial proliferation/regeneration in rats with experimental acute myocardial infarction]

Abstract

Objective: To investigate the myocardial proliferation/regeneration capacities at different time points and at different parts of the heart post acute myocardial infarction (AMI) in rats.

Methods: A total of 64 adult Sprague-Dawley (SD) rats were randomly divided into AMI group (left anterior descending coronary ligation, n = 44) and sham-operated group (n = 20). Rats were sacrificed on day 3, 5, 7, 14 and 60 respectively post operation (n = 5-9 at each time point) and ventricular tissues were harvested. 5-Bromo-2-deoxyUridine (Brdu, 50 mg/kg) was injected intraperitoneally at 12 and 24 hours before sacrifice. Morphological and pathological changes of the myocardium were observed after HE staining. Brdu-positive and c-kit and Brdu double-positive cardiomyocytes were analyzed post immunohistochemistry and immunofluorescence staining. Striated structure of new cells was detected by PTAH staining. Alpha-sarcomeric actin antibody was used to identify new cardiomyocytes.

Result: Brdu-positive cardiomyocytes at border zone and non-ischemic zone were significantly increased at 5 days post AMI and peaked at 7th day post operation (Border zone, AMI: 1.26% ± 0.15% vs.Sham: 0.22% ± 0.06%, P < 0.01; right ventricle, AMI: 0.75% ± 0.12% vs.Sham: 0.18% ± 0.07%, P < 0.01). There was no significant difference between the two groups on the 60th post-operation day. Brdu-positive cells were 1.7-fold higher in infarct border zone than in the right ventricular area of AMI rats on the 7th post operation day (1.26% ± 0.15%, vs.0.75% ± 0.12%, P < 0.01) and was 1.4-fold higher on the 14th post operation day (0.77% ± 0.09%, vs.0.54% ± 0.11%, P < 0.01). PTAH staining evidenced myocardial striated structure inside the new cells. Immunofluorescent assay showed that parts of Brdu positive cells were myocardial actin positive, and the c-kit and Brdu double-positive myocardial cells were also observed. Most nuclei of tehse new cardiomyocytes were small and round-shaped.

Conclusions: Myocardial proliferation/regeneration increased significantly after AMI in rats, especially around the infarct border zone. The myocardial proliferation/regeneration was time-dependent. Parts of the new cardiomyocytes had some characteristics of cardiac stem cells. This study suggests that myocardial proliferation/regeneration may be activated after acute myocardial injury.