Neonatal glucocorticosteroid treatment causes systolic dysfunction and compensatory dilation 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 mug/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 versus 371 +/- 23 mg, p < 0.001) and reduced systolic function (end-systolic elastance: 1.24 +/- 0.43 versus 2.50 +/- 1.39 mm Hg/muL, p = 0.028). Cardiac output was maintained and end-diastolic volume was increased (84 +/- 23 versus 59 +/- 19 microL, p = 0.012) indicating a state of compensatory 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.
Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Miriam P
MP
Bal
Willem B
WB
de Vries
Feike R
FR
van der Leij
Matthijs F M
MF
van Oosterhout
Rolf M F
RM
Berger
Jan
J
Baan
Ernst E
EE
van der Wall
Frank
F
van Bel
Paul
P
Steendijk
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology; D004452:Echocardiography; D005938:Glucocorticoids / Q000494:pharmacology*; D006339:Heart Rate; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology; D013599:Systole / Q000187:drug effects; D013997:Time Factors
D005938:Glucocorticoids; D012965:Sodium Chloride; D003907:Dexamethasone