CARDIOVASCULAR SYSTEM

Circulation

Circulatory well-being in infants and children is dependent on progression of structural and functional maturation (see Chapter 59 and Chapter 60 ). An understanding of this age-dependent process is essential for the diagnosis and treatment of circulatory failure in infants and children.

Structural and Functional Development

The external shape of the heart is complete by 6 weeks' gestation, but an increase in myofibrillar density and maturation continues at least through the first year of postnatal life.^[5] During this time, myocytes are engaged in rapid protein synthesis and rapid cell growth, which requires a high intracellular concentration of nuclei, mitochondria, and endoplasmic reticulum. This greater number of nonelastic and noncontractile elements makes the neonatal myocardium stiffer (less compliant) and less efficiently contractile than adult myocardium.^[6] In the fetus and newborn infant, because of this decreased ventricular compliance, even small changes in end-diastolic volume cause large changes in end-diastolic pressure. In addition, augmentation of stroke volume

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Development of the Circulation

The adult and fetal circulation differs in many ways. The fetal circulation is distinguished by (1) the placenta as the organ of respiration, (2) high pulmonary vascular resistance (PVR), (3) low systemic vascular resistance (SVR), and (4) the fact that the fetal ventricles pump in parallel with a dominant right ventricle.^[9] In addition, the fetus exists in a remarkably hypoxic environment compensated for by a relatively high cardiac output and hemoglobin with a high affinity for oxygen.^[10] The fetus compensates for placement of the placenta in the systemic circulation by several shunts: the ductus arteriosus, ductus venosus, and foramen ovale. When the fetus becomes an extrauterine being, the following important changes occur to bring the circulation to an adult form:

1. With the first breath, the increase in oxygen saturation, as well as other potential neurohumoral mediators and nitric oxide (NO), relaxes the pulmonary vasospasm that existed in utero. Pulmonary blood flow then increases as PVR decreases.^{[11] [12]}
2. The placenta separates from the uterine wall, the placental blood vessels constrict, and SVR and left ventricular afterload increase. As PVR decreases and SVR increases, left atrial pressures rise above right atrial pressure, and the "flap valve" of the foramen ovale^[13] functionally closes.
3. The fall in PVR results in reversal of flow through the ductus arteriosus. Blood flow from the aorta to the pulmonary artery exposes the ductus to oxygenated systemic arterial blood, which along with the rapid decrease in prostaglandin E₂ (PGE₂ ) blood levels after birth, contributes to closure of the ductus. The ductus is usually functionally closed during the first 24 hours of life, and anatomic obliteration follows throughout the next several weeks.^{[14] [15]}
4. The ductus venosus closes passively with removal of the placental circulation and readjustment of portal pressure relative to inferior vena cava pressure.^[16]
5. A further gradual decline in PVR occurs because of structural remodeling of the muscular layer of pulmonary blood vessels. During fetal life, the central pulmonary vascular bed has a relatively thick muscle layer. After birth, this muscle coat thins and extends to the periphery of the lung, a process that takes months and years to complete.^[17]

Development of Autonomic Control of the Circulation

The functional integrity of autonomic circulatory control during fetal and perinatal development is still a matter of considerable speculation. It has been shown in several species that the fetal heart has a reduced store of catecholamines and an increased sensitivity to exogenously administered norepinephrine.^[6] The sympathetic nerves first develop in the atria and grow into the ventricles toward the apex at a variable and species-specific rate.^[18]

In fetal lambs, resting α-adrenergic tone begins at approximately 0.6 gestation and is nearly complete at birth, but resting β-adrenergic control does not begin until 0.8 gestation and is incompletely developed at birth.^[19] Adrenergic innervation of the human myocardium may be complete between 18 and 28 weeks' gestation. However, low cardiac stores of norepinephrine, as well as a lack of fluorescence of sympathetic nerves, have been demonstrated in humans after birth. Adrenergic responses are apparently present but diminished in the newborn human. ^[20]

Development of cholinergic (vagal) control of the heart is also variable and species specific. In human newborn infants, the cholinergic system appears to be completely developed at birth, and the heart is sensitive to vagal stimulation.^[21] Such development provides for a relative vagal predominance of neural cardiovascular control and makes bradycardia a more likely response to any increase in autonomic tone.

The chemoreceptor and baroreceptor reflexes have important developmental implications in the infant and child; the baroreceptor reflex is present but incompletely developed at term in humans. In preterm infants, postural changes elicit no change in heart rate, but the increase in PVR that occurs is indicative of an incomplete and attenuated baroreceptor response.^[22] The chemoreceptor response seems to be well developed in utero. Fetal bradycardia in response to hypoxia is thought to be mediated through chemoreceptors and may be similar to the oxygen-conserving mechanisms of diving animals.^[23]

Myocardial Metabolism

Adult cardiac muscle is almost exclusively dependent on oxygen for its metabolism, and the efficiency of oxygen extraction is greater than in other organs. Anaerobic metabolism is nearly nonexistent in adult cardiac muscle, so the heart is extremely sensitive to hypoxia or ischemia. Either of these conditions, however brief, alters the energy supply and affects the mechanical response of the adult heart.

The metabolic characteristics of fetal myocardium are different. Relative hypoxia is normal in utero, and the infant's heart has been shown to tolerate hypoxia better than the adult's.^{[24] [25]} This difference may be partly due to high concentrations of glycogen in fetal myocardial tissue and the finding that the hypoxic fetal myocardium produces lactate, indicative of anaerobic metabolism.^[26] In addition, fetal hemoglobin is more efficient than adult hemoglobin in hypoxic environments. These mechanisms make the fetal/newborn heart relatively resistant to the destructive effects of hypoxia, provided that oxygenation and perfusion are reestablished within a reasonable period.

Myocardial demands change significantly in the first month of life. Oxygen consumption increases precipitously after birth, presumably because of thermogenesis. A full-term infant's oxygen consumption in a neutral thermal setting is approximately 5 mL/kg/min and increases to 7 and 8 mL/kg/min at 10 days and 4 weeks, respectively. Over the ensuing months, oxygen consumption and cardiac output gradually decline.^{[27] [28] [29]}