Effects of isoproterenol on the developing heart in rats

Many clinical clues suggest a link between abnormal catecholamine function during a phase of rapid cardiac development and hypertrophic cardiomyopathy. However, experimental investigation focusing on abnormal catecholamine function during the fetal period as the pathogenesis of hypertrophic cardiomyopathy has not yet been carried out. In this study, isoproterenol (ISO) was administered to pregnant female rats and the effects of the drug on the hearts of their offspring were studied morphologically. Fifty micrograms/kg/day of ISO was administered subcutaneously to 15 pregnant female rats 5 days a week for 3 weeks and the offspring were killed at 2 days, 4 weeks or 7 weeks after birth. Isotonic saline was administered to 15 pregnant female rats as control. The hearts of the offspring were removed and weighed immediately. The ventricles were cut in two, parallel to the atrio-ventricular groove. Left and right ventricular free wall thickness and interventricular septal thickness were measured. Under light-microscope, myocardial fiber diameter was measured and myocardial fiber disarray was assessed. Fine structural alterations of the cardiac muscle cells were observed by an electron microscope. The hearts of newborn offspring from pregnant rats treated with ISO showed disproportionate septal hypertrophy and frequent inter- and intra-cellular disarray in the interventricular septum. However, these changes were not prominent at 7 weeks after birth. These results suggest that abnormal catecholamine function during the fetal period may result in disproportionate septal hypertrophy.