Neonatal glucocorticosteroid treatment causes systolic dysfunction and compensatory dilatation in early life: Studies in 4-week-old prepubertal rats

Glucocorticosteroid treatment is widely used to prevent chronic lung disease in premature infants, Recent studies in adult rats, treated with dexamethasone in the neonatal period, report negative long-term effects on the heart and severely reduced life expectancy. We treated neonatal rats with dexamethasone and studied cardiac function after 4 wk (prepubertal age) to investigate whether the late effects as previously described are preceded by detectable alterations in cardiac function at a younger age. Male rat pups (n = 12) were injected intraperitoneally with dexamethasone on d 1, 2, and 3 (0.5, 0.3, and 0.1 mu g/g) of life. Control pups (n = 10) received saline. At 4 wk the animals were anesthetized, and a pressure-conductance catheter was introduced into the left ventricle to measure pressure-volume loops. Cardiac function was measured and pressure-volume relations were determined to quantify intrinsic systolic and diastolic function. Subsequently, hearts were excised for histologic examination. Compared with saline-treated animals, dexamethasone-treated rats had a reduced ventricular weight (270 +/- 40 Versits 371 +/- 23 mg, p < 0.001) and reduced systolic function (endsystolic elastance: 1.24 +/- 0.43 versus 2.50 +/- 1.39 min Hg/mu L, p = 0.028). Cardiac output was maintained and end-diastolic volume was increased (84 +/- 23 vervits 59 +/- 19 mu L p = 0.012) indicating it state of compensalory dilatation. Heart rate, diastolic function, and systemic vascular resistance were unchanged. Neonatal dexamethasone treatment causes cardiac alterations that can be detected in the prepubertal period and that may precede severe cardiac dysfunction later in life. If our findings are confirmed in humans. this may have consequences for a large patient population and cardiac screening at young age may be indicated to enable secondary prevention.