The Actions of Cardioactive Drugs on Developing Myocardium

Abstract

Clinicians have long recognized age related differences in cardiac pharmacology. These phenomena may reflect altered drug metabolism or disposition in the immature organism and/or an altered sensitivity of fetal and neonatal myocardium per se. The latter possibility was examined by studying the responsiveness to cardioactive drugs of heart muscle isolated from a total of 100 fetal, newborn, and adult sheep and swine. The enhancement of cardiac contractility produced by digitalis was significantly greater in newborn than adult heart. However, newborn myocardium required significantly more digitalis to achieve a peal inotropic effect or to demonstrate evidence of toxicity when compared to the adult. Fetal and adult cardiac muscle was equally responsive to isoproterenol, and acetylcholine. Fetal heart was supersensitive to the positive inotropic effects of norepinephrine. At all ages acidosis attenuated the augmentation of contractility produced by norepinephrine. Propranolol exerted a morc profound negative inotropic action on fetal than adult heart, although the effectiveness of beta adrenergic receptor blockade by propranolol was equal in fetal and adult myocardium. Glucagon exerted a negative inotropic effect on fetal cardiac muscle, a small positive inotropic effect in newborns, and a marked augmentation of contractility in the adult. Thus, a marked agedependency of the myocardial resonses to many cardioactive drugs exists that must be considered in any clinical evaluation of cardiac pharmacology in the perinatal period.