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/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.
Xu
Yi
Y
Department of Obstetrics/Gynecology, 232 HMRC, Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Williams
Sarah J
SJ
O'Brien
Darryl
D
Davidge
Sandra T
ST
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
D024022:Fibrillar Collagens; D007770:L-Lactate Dehydrogenase; D020778:Matrix Metalloproteinase 2; D018995:Myosin Heavy Chains