Intrauterine growth restriction coupled with hyperglycemia: effects on cardiac structure in adult rats

Abstract

Results Growth TrajectoriesBody weight. The offspring born to pregnant rats that were fed a low-protein diet (LPD) to induce IUGR are referred to here as "LPD offspring. " Offspring born to rats that had a normal-protein diet (NPD) are referred to as "NPD offspring. " At 3 d of age, the LPD offspring had body weights (BWTs) of 4.44 ± 0.13 g which were 24% lower than the weights of NPD offspring (5.74 ± 0.16 g) (P < 0.001). At 32 wk of age, the BWTs of the LPD offspring remained significantly lower than those of the NPD offspring (10% lower, P value relating to maternal diet (P D ) < 0.0001) (Figure 1a). When type 1 diabetes was induced, the increasing levels of blood glucose reduced (P value relating to hyperglycemic treatment (P T ) < 0.0001) the BWTs in LPD offspring as well as in NPD offspring. The maintenance of blood glucose levels at a mildly hyperglycemic level attenuated the effects of hyperglycemia on BWT in NPD offspring ( Figure 1a); however, the LPD offspring with mild hyperglycemia remained significantly smaller than the LPD control offspring. Articles IUGR combined with hyperglycemiaHeart weight. There was no significant difference in absolute heart weight in LPD offspring as compared with NPD offspring (1.95 ± 0.07 and 1.98 ± 0.04, respectively). However, when heart weights were adjusted to BWTs, LPD offspring exhibited significantly higher (P D = 0.05) relative heart weights as compared with NPD offspring at 32 wk of age (Figure 1b). The induction of hyperglycemia led to a marked increase (P T = 0.0002) in absolute heart weight in both LPD and NPD offspring. Furthermore, relative heart weight was also higher in all groups with hyperglycemia (P T < 0.0001), with moderately hyperglycemic LPD offspring exhibiting the highest heart weight relative to BWT (Figure 1b). Blood PressureBlood pressure remained constant throughout the measurement period, from 24 to 32 wk of age, in both LPD and NPD offspring (Figure 2a). There was no significant effect of hyperglycemia on blood pressure over the experimental period (Figure 2a). Echocardiographic AnalysesHeart rate. Heart rate was not affected by maternal protein restriction or the induction of hyperglycemia in either LPD or NPD offspring at 32 wk of age (Figure 2b).End-diastolic internal diameter of the left ventricle. Maternal protein restriction during pregnancy and lactation led to a significant reduction (P D < 0.0001) in the end-diastolic internal diameter of the left ventricle (LVIDd) of LPD offspring as compared with control NPD offspring (Figure 3a). There was a marked increase in the LVIDd in response to the induction of hyperglycemia (P T = 0.0008). However, the response to hyperglycemia was not significantly different between LPD and NPD offspring (P D×T = 0.2). Post hoc analyses demonstrated a significant increase (P < 0.05) in the LVIDd in LPD offspring with moderate hyperglycemia as compared with LPD control offspring; however, the LVIDd was normalized when blood glucose levels were reduced to mildly hyperglycemic levels.When the LVIDd was ad...

Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy

“…These permanent alterations become detrimental when the individual is exposed to a relative overabundance of nutrients in the postnatal period, predisposing to the metabolic syndrome and type 2 diabetes mellitus, adding to the cardiovascular risk (79). In support of this hypothesis, in a rat model of IUGR, cardiac interstitial fibrosis was not only greater in growth resticted compared to AGA rats, but greatest in those growth restricted exposed to hyperglycemia, demonstrating a synergistic effect of IUGR and metabolic derangement (80).…”

Impaired myocardial performance in a normotensive rat model of intrauterine growth restriction

“…Accordingly, Tintu et al (5) described the phenotype of a dilated cardiomyopathy and an increased expression of VEGF in chick embryos after hypoxia-induced IUGR. In contrast to our findings, Lim et al (7) did not detect any changes in myocardial capillarization in female IUGR rats. These conflicting data might arise from gender differences, different modes of low protein feeding, or different time points investigated.…”

“…At least a trend toward reduced cardiac output was also observed in another low protein model of IUGR (16). Lim et al (7) studied cardiac function in IUGR rats at an older age and in contrast to Cheema et al (8) found reduced LVEDD and normal ejection fraction. The reasons for this discrepancy remain unclear but may include different modes of low protein feeding (during pregnancy only vs. during pregnancy and lactation) and different time points investigated (8).…”

“…Crispi et al (6) showed that overt changes of myocardial structure and functionality occurred in IUGR patients already in childhood. There are, however, conflicting reports on myocardial functionality in rat models of IUGR: Lim et al (7) detected cardiac hypertrophy without impairment of myocardial performance in adult individuals after IUGR, while Cheema et al (8) described a reduced cardiac output in juvenile IUGR animals.…”

When early life growth restriction in rats is followed by attenuated postnatal growth: effects on cardiac function in adulthood

“…It is possible that as the LPD offspring grow older, overt cardiac dysfunction may become apparent. However, in a recent study, echocardiographic analysis in male LPD offspring at 32 weeks of age showed no evidence of cardiac dysfunction [34]; female LPD offspring were not examined in that study.…”