Biochemical, molecular and hemodynamic changes can fundamentally alter the functionality of the cardiomyocyte, and hence understanding the regulatory factors in cardiomyocyte function is 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.
Pressurized blood vessels serve as an excellent model system for the study of vascular function. Isolated and cannulated vessels are mounted in specialized chambers, known as pressure myographs, that allow for the control of flow and/or pressure, while simultaneously permitting introduction of pharmacologic agents and other vasoactive compounds.
Proper maintenance of many cell types in culture extends beyond temperature and media. Electro-stimulation can be used in conjunction with normal tissue culture conditions to help maintain cellular phenotype or induce differentiation from progenitor cell populations. Several scientists have shown that stimulated mechanical activity of cardiac myocytes in culture retains cell phenotype while also retaining contractile characteristics. Chronic stimulation in culture allows expression of virally transfected proteins while maintaining the ability to study contractile function. Electro-stimulation can also induce cardiac pre-commitment of stem cells, as well as differentiation of embryonic stem cells to a neurological phenotype. Similarly, chronic culture pacing can be used to induce de-novo sarcomere formation in incompletely differentiated C2C12 myotubes.
Lying between single cell and whole heart experimental studies, intact papillary muscle isolated from hearts offers unique advantages. Unlike single isolated myocytes, which represent the smallest fully functional model system, intact papillary muscle can be used to study cardiac function within a multicellular context and an intact 3-dimensional myofilament lattice.