Cardiovascular Susceptibility to Acute Myocardial Ischemic Injury in Male And Female Rat Offspring Born Growth Restricted

Abstract

BackgroundIschemic heart disease causes the greatest mortality in the world today. Epidemiological and animal studies have shown that populations who suffer intrauterine growth restriction (IUGR), one of the most common consequences of complicated pregnancies, are more susceptible to develop cardiovascular disorders in later life. We tested the hypothesis that adult male and female IUGR rat offspring are more susceptible to develop cardiac dysfunction following acute myocardial ischemic injury.MethodsMale and female control or IUGR rat offspring (created by exposing pregnant dams to hypoxia, 11.0±0.5% O2, for the last third of pregnancy) were randomly assigned to undergo sham or myocardial infarction (MI) surgery (by ligation of the left anterior descending coronary artery) at the age of 12 weeks. Thus the experimental groups consisted of: Control‐sham, Control‐MI, IUGR‐sham, and IUGR‐MI. One week after MI surgery, echocardiography was performed to assess cardiac morphometry, systolic function and diastolic function.ResultsFemale, but not male, IUGR offspring had lower body weight compared to controls at 12 weeks of age post 1 week of MI. Anterior left ventricular (LV) wall thickness was decreased whereas LV internal diameter during diastole was significantly increased in both control‐MI and IUGR‐MI groups independent of sex or IUGR; indicating wall thinning and LV dilatation due to MI. Ejection fraction, fractional shortening and fractional area change were significantly decreased in both control‐MI and IUGR‐MI groups in male and female offspring. The Tei index was significantly increased in both control‐MI and IUGR‐MI male groups. Interestingly, E/E’ ratio, an index of ventricular filling pressure, was significantly increased in only male IUGR‐MI group compared to IUGR‐Sham (IUGR‐Sham vs IUGR‐MI: 19.84 ± 2.13 vs 35.21 ± 3.66, P<0.05) and control‐MI (Control‐MI vs IUGR‐MI: 22.37 ± 1.73 vs 35.21 ± 3.66, P<0.01).ConclusionIschemic heart disease such as MI was shown to alter LV wall morphometry leading to LV dilatation in both sexes. MI impaired systolic function independent of being born growth‐restricted or sex. However, male IUGR offspring were more susceptible to develop diastolic dysfunction following acute MI. These studies indicate a susceptibility of the male IUGR population to develop diastolic heart failure due to acute myocardial ischemia.Support or Funding InformationThis work is funded by grants from the Canadian Institutes of Health Research (CIHR); and the Women and Children's Health Research Institute (WCHRI) through the generous contributions of the Stollery Children's Hospital Foundation (SCHF) and the Royal Alexandra Hospital Foundation (RAHF). A shah is supported by fellowships from the Heart and Stroke Foundation of Canada.