Impaired cardiac functional reserve and left ventricular hypertrophy in adult sheep after prenatal dexamethasone exposure

Miodrag Dodic, Chrishan Samuel, Karen Moritz, E. Marelyn Wintour, John Morgan, Leeanne Grigg, James Wong

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74 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)623-629
Number of pages7
JournalCirculation Research
Volume89
Issue number7
DOIs
Publication statusPublished - 28 Sept 2001
Externally publishedYes

Keywords

  • Dexamethasone
  • Hypertension
  • Left ventricular hypertrophy
  • Sheep

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