Experimentally induced intrauterine growth restriction in rabbits leads to differential remodelling of left versus right ventricular myocardial microstructure

Abstract

BACKGROUND: Intrauterine growth restriction (IUGR) affects up to 7-10% of pregnancies and is associated with fetal cardiac remodelling and dysfunction in utero together with increased risk of cardiovascular disease in adulthood. Experimental data concerning the effects of IUGR on cardiomyocyte and microvascularization anatomy are inconsistent and it is unknown whether both ventricles are similarly susceptible to in utero undersupply. METHODS AND RESULTS: IUGR was induced in pregnant New Zealand rabbits at 25 days of gestation by selective ligation of the uteroplacental vessels. Fetal echocardiography showed systolic and diastolic dysfunction of both ventricles in response to IUGR. Birth weight and heart weight were significantly reduced in the IUGR offspring. Design-based stereology revealed a decrease in cardiomyocyte number in both ventricles which was only in the left ventricle accompanied by a significantly higher cardiomyocyte mean volume. The proportion of mono- and bi-nucleated cardiomyocytes was unaltered between the groups indicating a similar maturation status. The number of cardiac capillaries in IUGR offspring was significantly diminished in left but not in right ventricles. CONCLUSIONS: We conclude that left and right ventricles are differently affected by placental insufficiency. While cardiomyocyte numbers are diminished in both ventricles, hypertrophic remodelling of cardiomyocytes and alterations in microvascularization is rather a left ventricular adaptation to IUGR. These unequal structural changes in response to IUGR may be related to developmental differences of the left and right ventricle.