In Utero Ventilation Augments the Left Ventricular Response to Isoproterenol and Volume Loading in Fetal Sheep

Abstract

The basis of this limitation in the ability of the fetal left ventricle to greatly increase output (systolic performance) is controversial. Several studies point to myocardial immaturity: incomplete development of sarcomeres (17-21), decreased functioning of {J-receptors (22, 23), and myofibrillar disarray (24,25) have all been implicated. Although fetal myocardium is certainly immature relative to that of the adult, none of these factors have been shown to change immediately at birth. In addition, many indices of systolic performance are increased in the newborn left ventricle relative to that of the adult (11,12), so that myocardial immaturity may not necessarily be associated with impaired ventricular function. It is remarkable that both the prematurely born animal (26-28) and human (29), which have not been exposed to prenatal hormone surges and labor to accelerate myocardial maturation, are capable of greatly increasing left ventricular output in response to a patent ductus arteriosus. In addition, recent studies of fetal sheep undergoing oxygen ventilation in utero have shown a doubling of left ventricular output (3,30), and other determinants of output such as septal compliance (31) have been shown to change in the perinatal period.Thus, left ventricular output may be limited in the fetus more because of its "circulatory environment" (the combination of a parallel circulation with central shunts, a dominant hypertrophied right ventricle that ejects more output and fills under similar pressures, a pulmonary vascular bed that is markedly constricted and that returns a very limited amount of blood to the left atrium and ventricle, and a highly compliant fetoplacental vascular bed that can absorb increases in volume that would otherwise increase left ventricular filling volume) than because of myocardial immaturity. For example, the fetal left ventricle has a very limited ability to increase output via the Frank-Starling mechanism (13), with a plateau occurring at 5-7 mm Hg. However, Hawkins et at.(32) have shown that some of this limitation is caused by a concomitant increase in afterload; if afterload is controlled, left ventricular output continues to rise at filling pressures of 10 mm Hg. In addition, high right ventricular filling and ejecting pressures may constrain left ventricular performance both in diastole and systole (33-36).We undertook the present study to determine whether the near-term (approximately 0.9 gestation) fetal left ventricle, functioning in a simulated "postnatal circulatory environment" (abolition of most central shunts with a small left to right shunt through the ductus arteriosus, a dominant left ventricle ejecting somewhat more blood than the right under higher filling pressures, a dilated pulmonary vascular bed returning a large amount of blood to the left atrium and ventricle, and a decrease in the fetoplacental vascular bed), is capable of increasing its output to levels similar to those seen in the newborn. We simulated the immediate postnatal circulatory environment in ute...

Effects of Lung Distension and Spontaneous Fetal Breathing on Hemodynamics in Sheep

“…There are several possible explanations for this. Although we have previously shown that in utero ventilation with oxygen may increase left ventricular output nearly 3-fold, it does so only when the fetus is supplied with additional blood volume and heart rate is increased by isoproterenol infusion (14). In the present study, plasma catecholamines increased with fetal breathing, but probably not to concentrations comparable to the level of /3-adrenergic receptor activation achieved by isoproterenol infusion.…”

Review article

“…According to TEYYEL et al [75], myocardial immaturity in fetuses of rabbit, cat and lamb includes incomplete development of sarcomeres, low functioning of beta-receptors, and myoflbrillar disarray.…”

Left ventricular torsional mechanics in term fetuses and neonates

“…The fetal heart at term is exposed to significant changes in volume and resistance load due to rapid fetal growth and, as a neonate, to the cardiorespiratory adaptation that occurs at delivery. The resultant changes in myocardial performance have been studied in fetal lambs, but the extent to which these acute cardiovascular changes influence perinatal cardiac adaptation has been explored inadequately in humans. Recent advances in cardiac imaging modalities have facilitated an increased interest in rotational mechanics of the heart.…”