Hemodynamics of the Developing Cardiovascular System

The development of the heart represents an intriguing, yet poorly understood interrelationship of function and form. Early in development, the heart is a pulsatile musclewrapped tube that transforms through morphogenesis into a four-chambered, fourvalved pump with separate systemic and pulmonary circulations. The cellular processes involved in morphogenesis are an intriguing aspect of cardiac development. The eventual shape and function of the heart is a complex interrelationship of genetics and epigenetics. The biochemical forces generated by the embryonic heart participate in the ultimate shape through modulation of the developmental process. Our research team has spent the last decade studying the interrelationship of function and form in cardiac development. This chapter summarizes our extensive studies of normal hemodynamic function and new work that links work load and heart growth. We have chosen the chick embryo model for several reasons. First, this is a widely accepted model of vertebrate heart development. Second, many laboratories are studying cellular and molecular biology of normal cardiac development. Third, the access to the chick embryo, although complicated, is not as difficult as a mammalian model. Accurate physiologic measurement required the adaptation of a variety of techniques to measure pressure and flow in the embryonic heart. We measured blood flow with a 20 MHz pulse Doppler velocity system and piezoelectric crystals between 0.5 and 0.75 mm in diameter.' Pressure measurements were made with a servo-null micropressure system from 5 micron diameter probes inserted into the various portions of the cardiovascular system.' These techniques have been detailed in our previous publications and are now used by other laboratories in their own studies of cardiovascular de~elopment.~.~ The period of initial heart formation is characterized by morphogenesis of the heart and by rapid growth of the embryo and the extraembryonic vascular bed. The primary function of the cardiovascular system is to meet the metabolic demands of the body, delivering nutrients and removing metabolic waste products from areas of rapid growth. Remarkably, the heart continues these roles during the process of heart formation and adaptation of marked hemodynamic demands. Growth of the embryo and the extraembryonic bed is extremely rapid. From stage 12 to 29,4 there is nearly a 120-fold increase in embryo mass (FIG. 1). During this time, the extraembryonic vascular bed responsible for gas exchange and nutrient delivered from the yolk sac increases only 30-fold. The relative weight of the ventricle