Limitation of heart growth in neonatal piglets by simvastatin and atorvastatin: comparison with pravastatin

The pig heart grows rapidly in the first few days after birth. We examined the effects of simvastatin, atorvastatin, and pravastatin on heart growth i n piglets. After vehicle, 2 mg . kg(-1) . day(-1) simvastatin, 2 mg . kg(-1 ) . day(-1) atorvastatin, or 4 mg . kg(-1) . day(-1) pravastatin were admin istered orally for 6 days, the thoracic cavity was opened, and the heart wa s removed under pentobarbital sodium (30 mg/kg ip) anesthesia. The heart wa s perfused to remove residual blood. After the heart was blotted dry, the r ight and left ventricular free walls were dissected. Each free wall was wei ghed and used for determination of DNA, RNA, and protein concentrations and mitogen-activated protein (MAP) kinase activity. Simvastatin and atorvasta tin resulted in smaller increases with age in the weight, concentrations of RNA and protein, and activity of MAP kinase in the left ventricular free w all, whereas pravastatin did not. The parameters of heart growth in the rig ht ventricular free wall were not appreciably affected by either drug. The blood pressure and heart rate were not changed by the treatments. These res ults suggest that simvastatin and atorvastatin interfere with heart growth in neonatal piglets after birth, especially in the left ventricular free wa ll.