Iribe G, Helmes M, Kohl P. Force-length relations in isolated intact cardiomyocytes subjected to dynamic changes in mechanical load. Am J Physiol Heart Circ Physiol 292: H1487-H1497, 2007. First published November 10, 2006; doi:10.1152/ajpheart.00909.2006.-We developed a dynamic force-length (FL) control system for single intact cardiomyocytes that uses a pair of compliant, computer-controlled, and piezo translator (PZT)-positioned carbon fibers (CF). CF are attached to opposite cell ends to afford dynamic and bidirectional control of the cell's mechanical environment. PZT and CF tip positions, as well as sarcomere length (SL), are simultaneously monitored in real time, and passive/active forces are calculated from CF bending. Cell force and length were dynamically adjusted by corresponding changes in PZT position, to achieve isometric, isotonic, or work-loop style contractions. Functionality of the technique was assessed by studying FL behavior of guinea pig intact cardiomyocytes. End-diastolic and end-systolic FL relations, obtained with varying preload and/or afterloads, were near linear, independent of the mode of contraction, and overlapping for the range of end-diastolic SLs tested (1.85-2.05 m). Instantaneous elastance curves, obtained from FL relation curves, showed an afterload-dependent decrease in time to peak elastance and slowed relaxation with both increased preload and afterload. The ability of the present system to independently and dynamically control preload, afterload, and transition between end-diastolic and endsystolic FL coordinates provides a valuable extension to the range of tools available for the study of single cardiomyocyte mechanics, to foster its interrelation with whole heart pathophysiology. single cell mechanics; preload; afterload; time-varying elastance CLASSICALLY, LOAD-DEPENDENT characterization of cardiac mechanics has been conducted in whole heart preparations (25,27). The externally homogeneous mechanical activity at this level (i.e., the whole organ) arises from spatiotemporal integration of the ordered, but intrinsically heterogeneous, activity of cardiac muscle elements (14). Currently, the tools to study mechanical interaction of heterogeneous contractile elements in near-physiological conditions are limited (23), and the vast majority of research on single intact cardiomyocytes is conducted in mechanically unloaded cells (15).