ABSTRACT. The purpose of these studies was to evaluate the effects of chronic caffeine ingestion on the myocardium during fetal and neonatal growth and development. The isolated perfused working heart preparation was used to evaluate cardiac function. During gestation and lactation, one group of dams consumed a caffeine supplemented diet (10 mg/kg/day). Their offspring were sacrificed and the hearts analyzed 50 days after birth. We found that the intake of caffeine by the dams resulted in significant increases in the offspring's coronary flow, peak systolic pressure, and myocardial work. A second group of dams ingested a diet containing caffeine (10 mg/kg/day) during lactation only. Their pups continued to consume the caffeine diet until 50 days. Caffeine is extensively used (I, 2) and therefore much concern has arisen concerning its potential for developmental toxicity. Caffeine is known to affect the central nervous system, cardiac muscle, cardiac output (2-4), blood pressure, heart rate (I), catecholamine release, and renin activity (2, 5, 6). Although the exact mechanisms of caffeine's cardiovascular effects are still controversial (7), the reports imply that the organism rapidly develops a tolerance to caffeine's acute actions and that the acute effects do not persist (5,8).Presently, insufficient information is available regarding chronic caffeine administration during early growth and development. Researchers have reported that caffeine and its metabolites readily cross the placenta and distribute evenly in fetal Received June 25, 1986; accepted November 26, 1986 tissue (9-12). During pregnancy, all the caffeine may not be metabolized (13,14) possibly causing an accumulation in maternal and fetal tissues. Caffeine has also been found in mother's milk (15, 16); thus, caffeine is available to the suckling infant. In addition, caffeine is known to activate the sympathetic nervous system, evaluate plasma free fatty acids (17-20), and decrease adipocyte size (2 1).The purposes of the present study were: (a) to determine whether caffeine ingestion by dams during fetal development and lactation had any long-term effect on the offspring's cardiac performance 50 days after birth, (b) to ascertain whether caffeine intake by the offspring during nursing and after weaning resulted in cardiac dysfunction in 50-day-old rats, and (c) to evaluate whether chronic caffeine consumption for 50 days during lactation and postweaning affected adipocyte size and number.
METHODS
Effect of caffeine intake during gestation and lactation.Timed pregnant (known date of conception) Sprague-Dawley rats (Holtzman Co., Madison, WI) were fed Purina Laboratory Chow at our animal facility. On day 13 of pregnancy (sperm positive as day I), randomly selected dams in the control group were fed a 20% protein diet (22). These control dams were fed ad libitum.On delivery, several litters were combined if the delivery time was within an 8-h range. Randomly selected pups were then assigned to each dam and the dams consumed the same diet during lacta...
