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

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 (beta/alpha 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, beta/alpha 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.