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

1 Department of Pharmacology, Hokkaido College of Pharmacy, Otaru 047-0264, Japan; and 2 Sigfried and Janet Weis Center for Research, Pennsylvania State University, Danville, Pennsylvania 17822-2614 The pig heart grows rapidly in the first few days after birth. We examined the effects of simvastatin, atorvastatin, and pravastatin on heart growth in 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 administered orally for 6 days, the thoracic cavity was opened, and the heart was removed under pentobarbital sodium (30 mg/kg ip) anesthesia. The heart was perfused to remove residual blood. After the heart was blotted dry, the right and left ventricular free walls were dissected. Each free wall was weighed and used for determination of DNA, RNA, and protein concentrations and mitogen-activated protein (MAP) kinase activity. Simvastatin and atorvastatin resulted in smaller increases with age in the weight, concentrations of RNA and protein, and activity of MAP kinase in the left ventricular free wall, whereas pravastatin did not. The parameters of heart growth in the right ventricular free wall were not appreciably affected by either drug. The blood pressure and heart rate were not changed by the treatments. These results suggest that simvastatin and atorvastatin interfere with heart growth in neonatal piglets after birth, especially in the left ventricular free wall. mitogen-activated protein kinase