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Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring

Yi Xu^*,1, Sarah J. Williams^*,,1, Darryl O’Brien^* and Sandra T. Davidge^*,2

^* Departments of Obstetrics/Gynecology and Physiology, Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada; and

Physiology, Centre for the Early Origins of Adult Health, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia

²Correspondence: 232 HMRC, Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. E-mail: sandra.davidge{at}ualberta.ca

ABSTRACT

Intrauterine growth restriction (IUGR) increases the risk of developing adult-onset cardiovascular disease. We hypothesized that IUGR resulting from maternal hypoxia or nutrient restriction during late gestation will produce cardiac remodeling and impair cardiac recovery after ischemia/reperfusion (I/R) in adult male offspring aged 4 or 7 mo. Sprague-Dawley rats were randomized on day 15 of pregnancy to hypoxia (IUGR-H, 12% oxygen), nutrient restriction (IUGR-NR, 40% of control diet) or control (room air) groups. In 4-mo IUGR-H offspring, left ventricular wt/body wt ratio (LVW/BW) and right ventricular wt/BW ratio (RVW/BW) increased, in association with increased collagen I and III expression, beta and alpha myosin heavy chain (ß/MHC) ratio, and decreased matrix metalloproteinase (MMP)-2 activity compared to the other groups. Left ventricular end diastolic pressure was higher in perfused hearts. Functional recovery after I/R was remarkably reduced (10±3%) compared to both control (39±5%) and IUGR-NR rats (32±4%). At 7 mo, both IUGR-H and IUGR-NR offspring had increased LVW/BW, collagen I and III, ß/ MHC ratio, and decreased cardiac recovery and MMP-2 activity compared to control. These findings suggest that hypoxia or undernutrition during development leads to pathological cardiac remodeling, diastolic dysfunction, and increased sensitivity to ischemic injury during adult life.—Xu, Y., Williams, S. J. O’Brien, D., and Davidge, S. T. Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring.

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