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Physiology of the Developing Heart Helena M Gardiner Keywords Fetal; Cardiovascular; physiology Introduction The heart is the first organ to become fully functional in the developing embryo, providing the circulatory system necessary for embryogenesis and subsequent fetal development when growth cannot be sustained by diffusion of nutrients Rapid advances in genetics and molecular biology have revolutionized our knowledge of the developing embryonic heart Furthermore, technical improvements in imaging and noninvasive physiologic recording of the early human fetus have enabled us to build on information from studies of animal models.1 Improved technology has also provided new insights into human cardiovascular development in disease states, and fetal responses to intrauterine challenges can be measured noninvasively This chapter reviews current understanding of the physiology and pathophysiology of the fetal cardiovascular system and discusses current evidence for the longer-term impact of fetal adaptations on subsequent development in childhood and beyond Embryonic Circulation In the chick embryo, rhythmic pulsations of approximately 50 Hz begin in the ventricle, coincident with fusion of cushions in the ventriculoarterial segment These pulsations are insufficiently forceful to set blood in motion or to generate recordable pressures.2 This is because the organization of intracellular contractile proteins is incomplete at this stage, the functional contractile units are not fully assembled, and the matrix of collagen has not yet formed.3 Once cardiac rhythm is established, the myofibrils within the myocytes become aligned and, as the heart rate rises, the direction of flow of blood is established to provide a circulation for the growing embryo Growth of the atriums and ventricles is associated with an increase in the rate of pulsation of the primitive heart tube This establishes the direction of propagation of the peristaltic waves of contraction from atrium to ventricle Cardiac myocytes isolated from the venous sinus, atrium, and ventricle at this developmental stage in the chick embryo all exhibit automaticity with different intrinsic rates of contraction The ventricle is slowest, at approximately 50 to 60 Hz, whereas cells from the venous sinus have the fastest rate, with the atrium being intermediate The earliest recordings of human fetal cardiac activity were obtained using high-frequency transvaginal ultrasound at 25 days after fertilization The mean heart rate at this stage of gestation is approximately 90 beats per minutes and regular This most likely represents atrial rhythm The mechanism responsible for the characteristic early increase in heart rate between the fifth and eighth weeks of gestation is uncertain but is comparable to that occurring in the chick embryo In chicks, it is associated with the transition of the pacemaker, first from ventricle to atrium as fusion occurs between the two, and then to the venous sinus as this segment becomes incorporated into the right atrium The precursor of the sinus node, which assumes the role of the cardiac pacemaker subsequently, forms at the junction of the developing superior caval vein with the atrium By 8 to 10 weeks, the mean heart rate in the human fetus varies between 160 and 170 beats/min, declining to an average of 150 beats/min at 15 weeks After this, the rate declines progressively toward term (Fig 6.1).4 This pattern of change in heart rate, seen during embryonic and fetal life in the human, also parallels that occurring in the chick, in which cardiac action begins between 33