Moderate preterm birth affects right ventricular structure and function and pulmonary artery blood flow in adult sheep.

Abstract

Preterm birth occurs when the heart muscle is immature and ill-prepared for the changes in heart and lung function at birth. MRI imaging studies show differences in the growth and function of the heart of young adults born preterm, with the effects more pronounced in the right ventricle. The findings of this study, conducted in sheep, showed that following moderate preterm birth the right ventricular wall was thinner in adulthood, with a reduction in the number and size of the heart muscle cells; in addition, there was impaired blood flow in the main artery leading from the right ventricle to the lungs. The findings indicate that being born only a few weeks early adversely affects the cellular structure of the right ventricle and blood flow to the lungs in adulthood. The reduced number of heart muscle cells has the potential to deleteriously affect right ventricular growth potential and function. Preterm birth prematurely exposes the immature heart to the haemodynamic transition at birth, which has the potential to induce abnormal cardiac remodelling. Magnetic resonance imaging studies in young adults born preterm have shown abnormalities in the gross structure of the ventricles (particularly the right ventricle; RV), but the cellular basis of these alterations is unknown. The aim of this study, conducted in sheep, was to determine the effect of moderate preterm birth on RV cellular structure and function in early adulthood. Male singleton lambs were delivered moderately preterm (132±1days; n=7) or at term (147±1days; n=7). At 14.5months of age, intra-arterial blood pressure and heart rate were measured. Pulmonary artery diameter and peak systolic blood flow were determined using ultrasound imaging, and RV stroke volume and output calculated. Cardiomyocyte number, size, nuclearity and levels of cardiac fibrosis were subsequently assessed in perfusion-fixed hearts using image analysis and stereological methods. Blood pressure (systolic, diastolic and mean), heart rate, levels of myocardial fibrosis and RV stroke volume and output were not different between groups. There was, however, a significant reduction in RV wall thickness in preterm sheep, and this was accompanied by a significant reduction in peak systolic blood flow in the pulmonary artery and in RV cardiomyocyte number. Cellular changes in the RV wall and reduced pulmonary artery blood flow following preterm birth have the potential to adversely affect cardiac and respiratory haemodynamics, especially when the cardiovascular system is physiologically or pathologically challenged.