Published online before print September 13, 2001, doi: 10.1161/hh1901.097086
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© 2001 American Heart Association, Inc.
Integrative Physiology |
Impaired Cardiac Functional Reserve and Left Ventricular Hypertrophy in Adult Sheep After Prenatal Dexamethasone Exposure
From the Howard Florey Institute (M.D., C.S., K.M., E.M.W.), University of Melbourne and Department of Cardiology (J.M., L.G., J.W.), Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
Correspondence to Dr Miodrag Dodic, Howard Florey Institute, University of Melbourne, Parkville 3052, Victoria, Australia. E-mail m.dodic{at}hfi.unimelb.edu.au
Abstract — 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 (COmax-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 µg/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 COmax-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 COmax-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 (FSmax-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.
Key Words: dexamethasone • hypertension • left ventricular hypertrophy • sheep
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