Postnatal Development Shapes the Cardiac Response to Milrinone

Milrinone, a medication that expands the heart's pumping capacity, is commonly used in both children and adults. However, the way the heart responds to milrinone can differ based on how mature the heart is. This study investigated this by examining guinea pig hearts at different ages - neonatal (up to two days old), juvenile (four to ten days old), and adult (six months old).

The researchers found that as the guinea pig hearts matured, certain measurements such as left ventricular developed pressure, action potential duration, and calcium transient duration all increased. These changes are consistent with the heart's remodeling and improvement in its ability to convert electrical signals into muscle contractions as it matures.

When milrinone was introduced, it caused an increase in heart rate across all age groups, but the effect was most noticeable at high doses. Milrinone also enhanced the heart's contractility and relaxation, but the strength of this effect depended on the heart's age and was lessened when the heart was being paced at a high frequency.

Adult hearts showed the greatest increase in left ventricular pressure during normal rhythm and had a robust response to high doses of milrinone, which was less marked in neonatal hearts. The action potential duration and calcium transient duration were shorter in both neonatal and adult hearts, but showed minimal changes in juveniles, indicating a non-uniform developmental pattern.

The study concludes that milrinone has positive effects on the heart's rate, strength, and relaxation in all age groups, but the extent and sensitivity to milrinone's effects can vary with age. This suggests that the heart's maturity plays a significant role in how it responds to milrinone, highlighting the importance of considering a child's age when choosing and dosing this medication.