Cardiovascular disease is the leading cause of death in the industrialized world. The development of heart disease and, in turn, heart failure is most often a consequence of dysfunction within individual heart muscle cells, or cardiomyocytes. Individual cardiomyocytes represent the smallest fully functional model system of heart muscle that can be examined for ion regulation, force production, relaxation function, cell signaling, and gene expression. Biochemical, molecular and hemodynamic changes can fundamentally alter the functionality of the cardiomyocyte, and hence understanding the regulatory factors in cardiomyocyte function are essential in the discovery and development of therapeutic interventions. Studies utilizing isolated cardiomyocytes have yielded important information regarding cardiomyopathies including, but not limited to, myocardial infarction, atrial fibrillation and sudden adult death syndrome.
Striated muscle, like cardiac tissue, is characterized by the appearance of bands within the individual myocytes known as sarcomeres. These basic units of muscle are formed by the molecular machinery that drives contractility in heart. The rates of sarcomere shortening and relengthening, as well as the magnitude of shortening, provide an important indicator of contraction/relaxation dynamics. Our Myocyte Contractility System combines fast brightfield imaging with sarcomere and cell length detection algorithms and application-specific analysis software to deliver reliable quantification of cardiomyocyte contractile function. Analysis outputs include determination of ±ΔL/Δt (dL/dt), representing peak shortening/relengthening velocities, and percent shortening for both sarcomere and cell length (these measures are comparable to ejection/refilling Vmax, or maximal velocities, and FS, or fractional shortening, in whole heart studies).
Calcium is known to be one of the most important regulatory factors in cardiac myocyte function, and is the link between the electrical signals which ripple through the heart and myocyte contraction. Changes in calcium release and handling in individual myocytes can dramatically affect the downstream mechanical activity of the myocyte. Our Myocyte Calcium and Contractility System brings fast, accurate calcium measurements to all of the functionality of our contractility system. In addition to the analysis outputs mentioned above, users can also determine the tau value for calcium reuptake, an important measure of SERCA activity.
New for 2017, our MultiCell System offers fully-automated identification and mechanical phenotype quantification from hundreds of myocytes per hour without sacrificing any of the detailed and thorough analysis of our standard systems. Featuring a fast x-y-z position-programmable scanning microscope coupled with a novel image analysis method quantifying position, size, and orientation, MultiCell brings dynamic characterization of contraction-relaxation function into the 21st century with greater statistical power, better acquisition and analysis, and a more user-friendly design.
Small changes in sarcomere length can produce large changes in tension development, known as length dependant activation. Changes in sarcomere length are instrumental to regulation of contractile force, commonly known as the Frank-Starling Law. When a cardiomyocyte becomes stretched, for example with increased ventricular preload, the sarcomeres are also stretched, resulting in an increase in the force of contraction. To improve the physiologic fidelity of our systems, we’ve developed additional tools to facilitate the attachment and mechanical loading (stretching) of intact isolated myocytes. Our MyoStretcher combines motorized micromanipulators and a suite of components designed to simplify myocyte attachment, including a specially designed rotatable chamber. Mechanical loading and mechanical resistance to relaxation better mimic the mechanical environment of myocytes in the heart. The MyoStretcher attachments have been designed to enable largely isometric contractions that simulate whole heart isovolumic contractions (loaded auxotonic contractions are also possible), while resistance to relaxation improves the accuracy of diastolic calcium measurements. Coupling the MyoStretcher with our ultrasensitive OptiForce force transducer provides sub-nanoNewton force detection (typical forces are between 10-1000nN). And adding our fast length controller and MultiClamp software pushes the system’s capabilities even further, enabling work-loop measurements (analogous to pressure-volume, or P-V, loops in whole heart). The MyoStretcher can be easily integrated into an existing IonOptix Calcium/Contractility system and is available as a stand-alone system.
In order to provide even more functionality, we’ve recently partnered with Cairn and 89North to provide fluorescence imaging solutions that can be combined with our Contractility and MyoStretcher systems. These include both widefield and confocal options, so any number of studies are possible including calcium sparks and ROS detection.
The use of isolated cardiomyocytes as a model for scientific investigations is essential to our understanding of cardiac physiology and pathology as well as cardiac response to novel pharmaceuticals. IonOptix is proud to be a leader in the development of new tools that facilitate cardiovascular discovery.