title: Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring.
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 (beta/alphaMHC) 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.
authors.affiliation: Department of Obstetrics/Gynecology, 232 HMRC, Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Williams
authors.forename: Darryl
authors.initials: D
authors.lastname: O'Brien
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D048070:Fetal Nutrition Disorders / Q000209:etiology; D024022:Fibrillar Collagens / Q000378:metabolism / Q000648:ultrastructure; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology; D000860:Hypoxia / Q000150:complications; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
chemical_list: D024022:Fibrillar Collagens; D007770:L-Lactate Dehydrogenase; D020778:Matrix Metalloproteinase 2; D018995:Myosin Heavy Chains