This project will test whether (and how) features of actively contracting cardiac muscle (e.g., end-systolic stress-strain relation, interval-strength relation) can be quantitatively inferred from measurements in the intact left ventricle. Such inferences would help to evaluate the status of myocardial fiber functioning from measurements in intact hearts (potentially, even in the clinical setting).
Our specific aims are: 1) to examine the distribution (how homogeneous?) of muscle fiber shortening and end-systolic sarcomere lengths in beating ventricles; 2) to compare systolic pressure development when the heart is stimulated synchronously as opposed to its normal sequence of activation; 3) to compare average fiber stress and average strain derived from ventricular pressure and volume measurements to the simultaneously and directly measured stress and strain in an in situ papillary muscle from the same isolated heart during ejection and in isovolumic contractions; 4) to compare the papillary muscle to the left ventricle with regard to simultaneously measured descriptive characteristics of the force-interval relation [e.g., recirculation fraction, and resititution of mechanical contractility with time following a beat]; and 5) to test whether myocardial resistance in an excised muscle behaves similarly to ventricular resistance. We will use an isolated, supported canine heart preparation to study these questions. The heart is instrumented with 1) a balloon in the left ventricle to control chamber volume, 2) a linear displacement motor to control the length of a right-ventricular papillary muscle, and 3) a pair of sonomicrometer crystals to measure muscle length. Pressure in the ventricle and force exerted by the muscle are measured by suitable transducers. A unique combination of physiologic and engineering skills has allowed us to develop this highly controlled yet physiologically viable preparation. To study the patterns sarcomere lengths and shortening in the beating heart, we will combine radiological and histological approaches. Small beads inserted into the myocardium will be tracked via biplane cineradiography and an automated marker-locating system. The pattern of strain in several myocardial layers will be observed throughout the cardiac cycle. To relate this pattern to muscle fiber motion, we will calibrate with respect to fiber angles and sarcomere lengths measured histologically post mortem. Finally, myocardial resistance and the force-velocity relations will be assessed using an excised papillary muscle in which a steady-state of contracture has been induced by barium.
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