Impaired cardiac functional reserve and left ventricular hypertrophy in adult sheep after prenatal dexamethasone exposure.
We have shown that exposure of pregnant ewes to dexamethasone (11.5 mg/d for 2 days) at 27 days of gestation (term, 150 days) led to increased blood pressure and cardiac output in adult offspring. In this study, we hypothesized that dexamethasone-induced hypertension is associated with left ventricular hypertrophy and a reduced cardiac functional reserve (CO(max-0)). Six control animals (group C) and five dexamethasone-exposed animals (group D) were volume-loaded with Hemaccel until the wedge pressure was 13 mm Hg (baseline). The wedge pressure was held constant during an infusion of dobutamine at incremental doses (0.4 to 12 microgram/kg/min) while blood pressure and cardiac output were measured. The same protocol was repeated in each animal 5 days later under mild general anesthesia (1.5% isoflurane), when transthoracic echocardiography (M-mode) was obtained. Group D showed a reduced CO(max-0) in response to dobutamine during both conscious (89+/-22 versus 150+/-25 mL/kg/min in control; P<0.01) and anesthetized states (91+/-38 versus 156+/-56 mL/kg/min in control; P<0.05). Reduced CO(max-0) in group D was associated with higher left ventricular mass index compared with group C (2.6+/-0.67 versus 1.8+/-0.51 g/kg; P<0.05). In addition, group D showed a reduced cardiac contractility reserve (FS(max-0)) in response to dobutamine (21+/-22% versus 54+/-34% in group C; P<0.05). An impaired cardiac functional reserve in group D was associated with increased left ventricular type I collagen content. In conclusion, brief prenatal exposure to dexamethasone led to the development of hypertension, left ventricular hypertrophy, and reduced cardiac functional reserve in adult life.
Dodic
M
M
Howard Florey Institute, University of Melbourne, Department of Cardiology, Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia. m.dodic@hfi.unimelb.edu.au
Samuel
C
C
Moritz
K
K
Wintour
E M
EM
Morgan
J
J
Grigg
L
L
Wong
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003094:Collagen / Q000032:analysis; D003907:Dexamethasone / Q000009:adverse effects*; D004195:Disease Models, Animal; D004280:Dobutamine; D004452:Echocardiography; D005260:Female; D005780:Gelatin / Q000008:administration & dosage; D005938:Glucocorticoids / Q000009:adverse effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D007262:Infusions, Intravenous; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011108:Polymers / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011651:Pulmonary Artery / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012756:Sheep
D005938:Glucocorticoids; C115675:Hemaccel; D011108:Polymers; D004280:Dobutamine; D003907:Dexamethasone; D005780:Gelatin; D003094:Collagen