In mature cardiac muscle, both sarcolemmal Ca2+ influx and sarcoplasmic reticulum (SR) Ca2+ release contribute to the activation of myofilaments. However, little is known about the regulation of contractile function in embryonic myocardium (EM) during myofiber maturation. Recently, we have developed methods to investigate embryonic myocardial function in vitro using a custom biomechanics system. We propose to investigate in vitro developed force in EM in response to changes in muscle length (Frank-Starling Relations), stimulation protocol (Force-Interval Relations), and rate of muscle shortening (Force-Velocity Relations). Following the definition of excitation-contraction coupling in normal developing myocardium, we then propose to determine the relationship between experimentally altered myocardial growth and myofiber maturation. We will increase ventricular afterload by placing a suture around the conotruncus, reducing the diameter of the outflow tract and increasing afterload. Alternatively, we will place a suture around the developing left atrium, redirecting venous blood away from the developing left ventricle and reducing ventricular preload. Both of these experimental methods result in significant acute changes in ventricular function and chronic changes in ventricular growth and morphogenesis. These data will provide important new information on the regulation of normal myocyte maturation and myocyte adaptation to altered loading conditions. These data may also be of value in determining mechanisms for altered cardiac morphogenesis and function in the fetus and infant with congenital cardiac malformations.
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| Tobita, Kimimasa; Schroder, Elizabeth A; Tinney, Joseph P et al. (2002) Regional passive ventricular stress-strain relations during development of altered loads in chick embryo. Am J Physiol Heart Circ Physiol 282:H2386-96 |
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