[Effects of Ca2+ antagonist on cardiomyocytic apoptosis after experimental myocardial infarction].
OBJECTIVE
To explore the effects of Ca(2+) antagonist on apoptosis of cardiomyocytes after myocardial ischemia.


METHODS
The model of myocardial infarction was made by ligating left coronary artery in SD rats. In experimental group, the rats were administrated with Adalat through oral cavity (1 mg/kg) before operation and through peritoneal cavity (0.4 mg/kg 3 hours after operation. In ischemic control group the rats were injected with placebo and in normal control group the rats were treated with sham operation (no ligating left coronary artery) and placebo. The rats were killed 6 hours after operation, with their left ventricular function had been measured. Apoptotic myocardial cells were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) method, Fas and Bcl-2 proteins by the ABC immunohistochemistry method. Apoptosis indexes were calculated under high magnification field of microscopy.


RESULTS
The systolic pressure, end-diastolic pressure and dp/dt of left ventricle in experiment group were not significant different from those in the ischemic control group, they were 76.7+/-7.5/8.0+/-6.1 mm Hg vs. 74.9+/-11.1/11.6+/-8.3 mm Hg (P>0.05) and (777.3+/-128.6)mm Hg/s vs. (761.8+/-136.4)mm Hg/s (P>0.05) respectively; but those in both the experimental group and the ischemic control group were lower than those in the normal control group, they were 94.9+/-7.5/2.8+/-3.2 mm Hg (P<0.001) and (1131.5+/-112.8)mm Hg/s(P<0.001). There were a lot of positive myocytes with TUNEL stain in the ischemic region of left ventricle in both the experimental and the ischemic control group, apoptosis index in the experimental group was lower than that in the ischemic control group (0.201+/-0.053 vs. 0.261+/-0.045, P<0.05). The positive myocytes of Fas and Bcl-2 protein appeared in the region surrounding ischemic myocytes. There were no positive myocytes with the three types of stain in normal control group.


CONCLUSIONS
Ischemia could induce apoptosis of myocytes and expression of Fas and Bcl-2 gene; Ca(2+) antagonist could protect myocytes from apoptosis.
Feng
Quan-zhou
QZ
Department of Cardiology, General Hospital of Chinese PLA, Beijing 100853, China. fqz301@tom.com
Li
Tian-de
TD
Wang
Zhao-xia
ZX
Yi
Jun
J
Wang
Li
L
Yang
Ting-shu
TS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor
D002121:Calcium Channel Blockers; C491898:Fas protein, rat; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D009543:Nifedipine