Spatiotemporal Control of Human Cardiac Tissue Through Optogenetics

Cardiac arrhythmias are caused by disordered propagation of electrical activity. Progress in understanding and controlling arrhythmias requires novel methods to characterize and control the spatiotemporal propagation of electrical activity. We used patterned illumination of cardiomyocytes derived from optogenetic human induced pluripotent stem cells to create dynamic conduction blocks, and to test spatially extended control schemes. Using this model, we demonstrated the ability to initiate, circumscribe, relocate, and terminate pathologic spiral waves that drive many arrhythmias. When cells were derived from patients with long QT syndrome, longer action potential durations made spiral waves more resistant to termination. This work lays the foundation for personalized models of cardiac injury and disease, and the development of tailored approaches to the management of arrhythmias

Confocal laser scanning microscope, raman microscopy and western blotting to evaluate inflammatory response after myocardial infarction

Cardiac muscle necrosis is associated with inflammatory cascade that clears the infarct from dead cells and matrix debris, and then replaces the damaged tissue with scar, through three overlapping phases: the inflammatory phase, the proliferative phase and the maturation phase. Western blotting, laser confocal microscopy, Raman microscopy are valuable tools for studying the inflammatory response following myocardial infarction both humoral and cellular phase, allowing the identification and semiquantitative analysis of proteins produced during the inflammatory cascade activation and the topographical distribution and expression of proteins and cells involved in myocardial inflammation. Confocal laser scanning microscopy (CLSM) is a relatively new technique for microscopic imaging, that allows greater resolution, optical sectioning of the sample and three-dimensional reconstruction of the same sample. Western blotting used to detect the presence of a specific protein with antibody-antigen interaction in the midst of a complex protein mixture extracted from cells, produced semi-quantitative data quite easy to interpret. Confocal Raman microscopy combines the three-dimensional optical resolution of confocal microscopy and the sensitivity to molecular vibrations, which characterizes Raman spectroscopy. The combined use of western blotting and confocal microscope allows detecting the presence of proteins in the sample and trying to observe the exact location within the tissue, or the topographical distribution of the same. Once demonstrated the presence of proteins (cytokines, chemokines, etc.) is important to know the topographical distribution, obtaining in this way additional information regarding the extension of the inflammatory process in function of the time stayed from the time of myocardial infarction. These methods may be useful to study and define the expression of a wide range of inflammatory mediators at several different timepoints providing a more detailed analysis of the time course of the infarct

Aerospace Medicine and Biology. A continuing bibliography with indexes

This bibliography lists 286 reports, articles and other documents introduced into the NASA scientific and technical information system in March 1983

Intrapericardial Delivery of Gelfoam Enables the Targeted Delivery of Periostin Peptide after Myocardial Infarction by Inducing Fibrin Clot Formation

Background: Administration of a recombinant peptide of Periostin (rPN) has recently been shown to stimulate cardiomyocyte proliferation and angiogensis after myocardial infarction (MI). However, strategies for targeting the delivery of rPN to the heart are lacking. Intrapericardial administration of drug-eluting hydrogels may provide a clinically viable strategy for increasing myocardial retention, therapeutic efficacy, and bioactivity of rPN and to decrease systemic re-circulation. Methods and Results: We investigated the ability of intrapericardial injections of drug-eluting hydrogels to deliver and prolong the release of rPN to the myocardium in a large animal model of myocardial infarction. Gelfoam is an FDA-approved hemostatic material commonly used in surgery, and is known to stimulate fibrin clot formation. We show that Gelfoam disks loaded with rPN, when implanted within the pericardium or peritoneum of mammals becomes encapsulated within a non-fibrotic fibrin-rich hydrogel, prolonging the in vitro and in vivo release of rPN. Administration into the pericardial cavity of pigs, following a complete occlusion of the left anterior descending artery, leads to greater induction of cardiomyocyte mitosis, increased cardiomyocyte cell cycle activity, and enhanced angiogenesis compared to direct injection of rPN alone. Conclusions: The results of this study suggest that intrapericardial drug delivery of Gelfoam, enhanced by triggered clot formation, can be used to effectively deliver rPN to the myocardium in a clinically relevant model of myocardial infarction. The work presented here should enhance the translational potential of pharmaceutical-based strategies that must be targeted to the myocardium

Application of artificial intelligence techniques for automated detection of myocardial infarction: A review

Myocardial infarction (MI) results in heart muscle injury due to receiving insufficient blood flow. MI is the most common cause of mortality in middle-aged and elderly individuals around the world. To diagnose MI, clinicians need to interpret electrocardiography (ECG) signals, which requires expertise and is subject to observer bias. Artificial intelligence-based methods can be utilized to screen for or diagnose MI automatically using ECG signals. In this work, we conducted a comprehensive assessment of artificial intelligence-based approaches for MI detection based on ECG as well as other biophysical signals, including machine learning (ML) and deep learning (DL) models. The performance of traditional ML methods relies on handcrafted features and manual selection of ECG signals, whereas DL models can automate these tasks. The review observed that deep convolutional neural networks (DCNNs) yielded excellent classification performance for MI diagnosis, which explains why they have become prevalent in recent years. To our knowledge, this is the first comprehensive survey of artificial intelligence techniques employed for MI diagnosis using ECG and other biophysical signals.Comment: 16 pages, 8 figure

Cellular Cardiomyoplasty Based on Muscle Stem Cells: Implications for Therapy

Heart disease is the leading cause of death in the world and cellular cardiomyoplasty is an emerging therapeutic option to repair damaged myocardium. Muscle-derived stem cells (MDSCs) have been shown to have an improved regenerative capacity in bone, cartilage, and skeletal muscle when compared to myoblasts. After implantation into ischemic hearts, MDSCs display high levels of engraftment, induce neoangiogenesis, prevent cardiac remodeling, and elicit significant improvements in cardiac function. Notably, diversity in MDSC behavior has been associated with innate sex-related differences in skeletal muscle, bone, and cartilage. These results suggest that differences in inherent stem cell characteristics, including sex and age, could account for some of the outcome variability noted in clinical trials. Therefore we examined the effect of sex-related differences of MDSCs in cardiac repair. Transplantation of both cell sexes significantly improved cardiac function in comparison to saline. We also found that with increasing age, the proliferation and differentiation abilities of MDSCs decreased while their survival under stress conditions and vascular endothelial growth factor (VEGF) secretion remained unchanged. Our in vivo study demonstrates that the age of MDSCs does not impact their regenerative capacity but increasing the age of the host leads to decreased repair, which implies that the majority of age-related decreases in repair are due to changes in the microenvironment. We then examined methods to improve the efficacy of cell transplantation via preconditioning strategies. We first investigated the effects of mechanical stimulation on increasing the secretion of VEGF, which plays a major role in effecting cardiac repair after cell transplantation. Mechanical preconditioning significantly increased VEGF secretion, angiogenesis, and cardiac function after myocardial infarction, suggesting that this method of cell preconditioning could increase therapeutic efficacy. Another major issue with cell therapy is low cell survival after implantation. We hypothesized that increasing the level of antioxidants in MDSCs prior to transplantation could increase survival and therefore improve functional cardiac repair. We found that antioxidant pretreatment increased cell survival, cardiac function, and angiogenesis, and decreased scar formation. These pretreatment strategies have the potential to significantly improve the efficacy of cell transplantation and enhance the outcomes of heart disease patients