Response of the neonatal heart to a new inotropic agent, RO2-2985 (X537A)

The ionophore RO2-2985 did not produce a positive inotropic response in 1-day-old canine isolated ventricle. A gradual increase in inotropic response was seen with age. Isolated atria, however, exhibited a positive inotropic response at birth (50% increased dF/dt), which became progressively greater with age (100% increase in dF/dt at 15 days of age). In the neonatal heart in situ there was a positive inotropic response in 1-day-old puppies (40% increase in left ventricular dF/dt) with progressively greater responses with age (135% increase in left ventricular dF/dt at 11 days of age). There was a positive chronotropic (75-125% increase) response to RO2-2985 at all ages studied. The drug elevated systemic arterial pressure (150% increase in mean arterial pressure) to a similar degree in all ages studied. RO2-2985 depressed total calcium binding by both neonatal and adult isolated cardiac sarcoplasmic reticulum approximately 50%.