Andersons pediatric cardiology 159

mechanical improvement and may be important in future strategies for the management of cardiac failure.23 However, caution should be exercised in the interpretation of results from animal models A review of responses of the fetal gene program in the rodent model of cardiomyopathy in diabetes indicated that the most commonly measured genes in the fetal gene program are confounded by the diabetogenic effects.24 The myosin heavy chain carries the ATPase site The enzymic kinetics of ATPase are specific for each isoform This is important because it is the rate at which ATPase hydrolyzes ATP that primarily determines the force-velocity relationship during myocardial contraction This partly explains the differences in active and passive mechanics between fetal and adult myocardium.25 The transition from fetal to adult isoforms of myosin heavy chain around birth is similar to the controlled switch from fetal to adult hemoglobin and represents stage-specific regulation of genetic expression of the proteins prior to birth Although a number of hormones, and particularly thyroid hormone,26,27 are known to modulate the phenotypic expression of the myosin heavy chain, the factors responsible for the precise timing of the transition from fetal to adult isoforms remain unknown, although the molecular mechanisms are thought likely to be associated with the myosin heavy chain (MYH) gene cluster.28 Fetoplacental Circulation The fetal circulation has two circulatory systems arranged in parallel and characterized by five unique features that permit the delivery of oxygenated blood to the left side of the fetal heart from the placenta and direct systemic venous return away from the fluid-filled lungs and back to the placenta to become oxygenated The placental circulation is designed to maximize exchange of oxygen and nutrients between the mother and fetus The oxygenated blood flows in the umbilical vein into the fetal liver where a variable portion enters the venous duct This small vessel connects the intrahepatic portion of the umbilical vein to the inferior caval vein, and the higher velocity jet streams through the oval foramen into the left side of the heart This mechanism is essential for filling of the fetal left ventricle as the fetal lungs are fluid-filled and have a relatively low circulatory volume compared with their postnatal function The systemic venous return from the fetal body is ejected from the right ventricle, with the majority diverted away from the pulmonary circulation through the arterial duct, into the descending aorta below the level of the isthmus This deoxygenated blood returns to the placental circulation via the two umbilical arteries for oxygenation and receipt of nutrients Placenta The placenta plays a major role in the fetal circulation, fulfilling the functions of the lung for exchange of gases, and for the kidney and gastrointestinal tract in delivery of nutrients and excretion of metabolites The fetal side of the placenta, which develops from the chorion, receives blood from paired umbilical arteries, which take origin from the internal iliac arteries of the fetus The umbilical arteries within the cord spiral around the umbilical vein and then divide into branches at the junction of the cord and the placenta These branches have a radial disposition The terminal branches perforate the chorionic plate and form anastomotic plexuses within the main stem of each chorionic villus Each main stem possesses a derivative of the umbilical artery, which penetrates the thickness of the placenta, dividing to form a huge network of capillary plexuses These project into the intervillous spaces that contain maternal blood.29 As a result, there is a very extensive surface area within each chorionic villus, across which exchange of gas occurs down gradients for both oxygen and carbon dioxide There is essentially no mixing of maternal and fetal blood Following oxygenation within the chorionic villuses, the blood enters the venous radicals within each main stem These efferent venules become confluent at the junction of the placenta and umbilical cord to form the umbilical vein The normal umbilical cord shows a regular coiling of the umbilical vein and arteries (Video 6.1) that may be altered in disease states such as hypertension (discussed later) (Fig 6.2) FIG 6.2 (A) Grayscale image of segment of cord showing arterial redundancy (UA) over relatively straight umbilical vein (UV) (B) Power Doppler high-definition image of (A) showing arterial loops due to redundancy (arrows) In cases where there is marked increase in UA length, the artery is tortuous and there are segments where the artery reverses in direction similar to a fleur-de-lis This can be seen with (B) and without (A) color Doppler UA tortuosity or redundancy due to increased arterial length in relation is shown with color Doppler (C) and fetoscopically (D) during laser surgery (From Donepudi R, Mann LK, Wohlmuth C, et al Recipient umbilical artery elongation (redundancy) in twin-twin transfusion syndrome Am J Obstet Gynecol, 2017; 206.e1–206.e11.)