VENTRICULAR/VASCULAR COUPLING OF THE DEVELOPING CARDIOVASCULAR SYSTEM

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Tissue level, biomechanical regulation of cardiac function is a fundamental property of the developing cardiovascular system. This tissue level regulation is evident in the narrow operating range of control parameters such as heart rate, developed pressure, and stroke volume during normal development (Clark 1990a), and the ability of the embryonic heart to adjust mass to workload (Clark 1989a). Despite the ability to define the operating range of the embryonic circulation, we have not yet identified the fundamental mechanisms which determine the interaction between cardiovascular form and function. Of note, previous experiments were designed and analyzed with respect to a single cardiac element. Current research in the mature circulation supports the definition of the cardiovascular system as a closed loop, where the input, function, and output of each of the elements of the circuit are defined and related (Sunagawa 1984, Sagawa 1988a). This closed-loop framework allows the definition of cardiovascular regulation. Our long term aim is to define the tissue level regulatory mechanisms that produce the dynamic interdependence between embryonic cardiovascular function and morphology. We hypothesize that hemodynamic and mechanical coupling between the ventricle and vascular bed optimize function and influences morphogenesis. Our experimental models is the stage 16 to 24 white Leghorn chick embryo during the transition of ventricular geometry from a smoothwalled to a trabecular chamber. Our experimental methods are described in the Physiology Core, and include the simultaneous measurement of ventricular pressure, dorsal aortic pressure and flow, and video imaging. Our specific aims in this project are to first define the interaction of the embryonic ventricle and arterial bed during acute changes in the heart rate and activation sequence, preload, and vascular tone during normal development. We then define the interaction of the embryonic ventricle and arterial bed to changes in the heart rate, activation sequence, preload, and vascular tone following growth acceleration produced by conotruncal banding and growth deceleration produced by partial left atrial ligation. This project defines the functional interaction of the embryonic ventricle and arterial bed during wide range of acute and chronic alterations in hemodynamic performance. The analysis of experimental results within the framework of a closed loop system provides crucial information on the regulation of cardiovascular function. This integrated analysis then becomes the foundation for the structural and functional analysis of genetically altered cardiovascular systems in experimental models, and ultimately, aids in defining the underlying etiologies of congenital cardiovascular malformations.