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Multiscale modeling of cardiac electrophysiology helps to better understand the underlying mechanisms of atrial fibrillation, acute cardiac ischemia and pharmacological treatment. For this purpose, measurement data reflecting these conditions have to be integrated into models of cardiac electrophysiology. Several methods for this model adaptation are introduced in this thesis. The resulting effects are investigated in multiscale simulations ranging from the ion channel up to the body surface.

acute cardiac ischemia --- parameter adaptation --- pharmacological therapy --- atrial fibrillation --- cardiac modeling

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Mitochondria, organelles surrounded by a double membrane and with their own small genome, are the cells’ energy centers. Besides the production of ATP through cellular respiration, mitochondria play a pivotal role in other aspects of the life and death of a cell: heat production, programmed cell death, the regulation of metabolic activity, immunity, and calcium homeostasis. A number of diseases are associated with mitochondrial dysfunction, including cardiovascular, neurological, inflammatory, and metabolic disorders as well as cancer. Mitochondria therefore represent an important therapy target, and it is not surprising that a number of different treatment strategies have emerged. Approaches targeting mitochondria can be split into two opposite categories: drugs that restore mitochondrial function and drugs that trigger mitochondria-mediated cell death. Targeted drug delivery to achieve the selective accumulation of drug molecules in mitochondria is complex and involves methods such as direct drug modification or encapsulation into nanocarriers.

retinal ischemia --- blood–brain barrier --- endothelial --- reactive oxygen species --- oxidative stress --- tunneling nanotubules --- neuron --- central nervous system --- inflammation --- hypoxia --- anticancer peptide (ACP) --- antimicrobial peptide (AMP) --- anticancer peptides --- antimicrobial peptides --- host defense peptides --- prediction --- random forest --- mitochondria --- mitochondrial DNA --- mitochondrial disorders --- pharmacological therapy --- gene therapy --- precision medicine --- cardiovascular disease --- drug delivery --- mitochondria dysfunctions --- nanocarriers --- oxoglutarate carrier --- malate-aspartate shuttle --- cancer metabolism --- ATP production --- diphenyleneiodonium --- NADPH-oxidase --- differentiation --- proliferation --- mitochondria-targeted antioxidants --- LPS --- mitochondrial ROS --- antitumor agents --- fluorescence lifetime imaging --- medicinal chemistry --- metabolic drug --- mitochondrial carrier --- melanoma --- plumbagin --- cytotoxic effect --- metabolism --- cholesterol --- lipid raft --- mitochondrial permeability transition pore --- alkylphospholipid analog --- edelfosine --- mitochondrial oncometabolites --- cancer drug resistance --- mitochondrial disease --- heteroplasmy --- mitochondrial gene delivery --- n/a --- blood-brain barrier