Ontogenetic differences in cardiac sensitivity to verapamil in rats.

The degree of a negative inotropic response of the isolated right ventricle to verapamil as well as the mortality rate were studied in rats during their postnatal development. Male Wistar rats aged 3, 15, 30, and 90 days were used. The isolated right ventricle was incubated in a glucose-free solution with a mixture of 95% O2 and 5% CO2 and electrically stimulated. The amplitude of isotonic contractions (AIC) was registered. In 90-day-old rats, AIC was 74.1 +/- 6.2% of initial amplitude 45 min after administration of verapamil; in 30-day-old, 41.1 +/- 6.4%; in 15-day-old, 38.2 +/- 4.1%; and in 3-day-old rats, only 2.6 +/- 1.5. The difference between the 3-day-old rats and all older groups was statistically highly significant. The mortality rate of verapamil-treated rats increased with decreasing age of animals. It is concluded that the sensitivity of the rat myocardium to verapamil is age dependent: the negative inotropic effect of this drug increases with decreasing age of the animal. This indicates a possible risk in the therapeutic use of verapamil when given to newborns and infants.