PROGRAMMED MYOCYTE CELL-DEATH AFFECTS THE VIABLE MYOCARDIUM AFTER INFARCTION IN RATS

To determine whether apoptotic and necrotic myocyte cell death occur a cutely and chronically after infarction, the formation of DNA strand b reaks and the localization of myosin monoclonal antibody labeling were analyzed in the surviving myocardium from 20 min to 1 month. DNA stra nd breaks in myocyte nuclei were detected as early as 3 h following co ronary artery occlusion and were still present at 1 month. This cellul ar process was characterized biochemically by internucleosomal DNA fra gmentation which produced DNA laddering on agarose gel electrophoresis . Quantitatively, 155 myocyte nuclei per 10(6) cells exhibited DNA str and breaks in the portion adjacent to the infarcted tissue at 3-12 h. This parameter increased to 704 at 1-2 days and subsequently decreased to 364 at 7 days, 188 at 14 days, and 204 at 1 month. In the remote m yocardium, the number of myocyte nuclei with DNA strand breaks was 84 per 10(6) at 3-12 h and remained essentially constant up to 1 month. P rogrammed myocyte cell death was accompanied by a decrease in the expr ession of bcl-2 and an increase in the expression of bar. The changes in the expression of these genes were present at 1 and 7 days after co ronary artery occlusion. In conclusion, the mechanical load produced b y myocardial infarction and ventricular failure may affect the regulat ion of bcl-2 and bar in the viable myocytes, triggering programmed cel l death and the remodeling of the ventricular wall. (C) 1996 Academic Press, Inc.