Treatment with dimethylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice - Role of oxidativestress

Oxidative stress might play an important role in the progression of left ve ntricular (LV) remodeling and failure that occur after myocardial infarctio n (MI), We determined whether reactive oxygen species (ROS) are increased i n the LV remodeling and failure in experimental MI with the use of electron spin resonance spectroscopy and whether the long-term administration of di methylthiourea (DMTU), hydroxyl radical ((OH)-O-.) scavenger, could attenua te these changes. We studied 3 groups of mice: sham-operated (sham), MI, an d MI animals that received DMTU (MI + DMTU), Drugs were administered to the animals daily via intraperitoneal injection for 4 weeks,(OH)-O-. was incre ased in the noninfarcted myocardium from MI animals, which was abolished in MI + DMTU. Fractional shortening was depressed by 65%, LV chamber diameter was increased by 53%, and the thickness of noninfarcted myocardium was inc reased by 37% in MI. MI + DMTU animals had significantly better LV contract ile function and smaller increases in LV chamber size and hypertrophy than MI animals. Changes in myocyte cross-sectional area determined with LV mid- free wall specimens were concordant with the wall thickness data. Collagen volume fraction of the noninfarcted myocardium showed significant increases in the MI, which were also attenuated with DMTU, Myocardial matrix metallo proteinase-2 activity, measured with gelatin zymography, was increased with MI after 7 and 78 days, which was attenuated in MI + DMTU. Thus, the atten uation of increased myocardial ROS and metalloproteinase activity with DMTU may contribute, at least in part, to its beneficial effects on LV remodeli ng and failure. Therapies designed to interfere with oxidative stress might be beneficial to prevent myocardial failure.