RESUMO
Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by reductionist models and poorly simulated mechanical load profiles. This hinders the physiological relevance of findings. Living myocardial slices have been used to study load in vitro. Living myocardial slices (LMS) are 300-µm-thick intact organotypic preparations obtained from explanted animal or human hearts. They have preserved cellular populations and the functional, structural, metabolic and molecular profile of the tissue from which they are prepared. Using a three-element Windkessel (3EWK) model we previously showed that LMSs can be cultured while performing cardiac work loops with different preload and afterload. Under such conditions, LMSs remodel as a function of the mechanical load applied to them (physiological load, pressure or volume overload). These studies were conducted in commercially available length actuators that had to be extensively modified for culture experiments. In this paper, we demonstrate the design, development and validation of a novel device, MyoLoop. MyoLoop is a bioreactor that can pace, thermoregulate, acquire and process data, and chronically load LMSs and other cardiac tissues in vitro. In MyoLoop, load is parametrised using a 3EWK model, which can be used to recreate physiological and pathological work loops and the remodelling response to these. We believe MyoLoop is the next frontier in basic cardiovascular research enabling reductionist but physiologically relevant in vitro mechanical studies.
Assuntos
Reatores Biológicos , Coração , Animais , Humanos , Miocárdio , Projetos de PesquisaRESUMO
Vascular and valvular calcifications, commonly seen in renal patients, increase operative mortality and can preclude conventional valvular management. We show a novel approach to treat aortic stenosis and degenerative mitral regurgitation under hypothermic circulatory arrest in a hemodialysis patient with aortic, mitral disease and porcelain aorta with surgical and transcatheter contraindications.
RESUMO
In recent years, development of mechanical circulatory support devices has proved to be a new treatment modality, in addition to standard pharmacological therapy, for patients with heart failure or acutely depressed cardiac function. These include left ventricular assist devices, which mechanically unload the heart when implanted. As a result, they profoundly affect the acute cardiac mechanics, which in turn, carry long-term consequences on myocardial function and structural function. Multiple studies have shown that, when implanted, mechanical circulatory assist devices lead to reverse remodelling, a process whereby the diseased myocardium reverts to a healthier-like state. Here, we start by first providing the reader with an overview of cardiac mechanics and important hemodynamic parameters. We then introduce left ventricular assist devices and describe their mode of operation as well as their impact on the hemodynamics. Changes in cardiac mechanics caused by device implantation are then extrapolated in time, and the long-term consequences on myocardial phenotype, as well as the physiological basis for these, is investigated.