Myocardiale Ischemie-Reperfusie schade: Inflammatoire Inzichten en Visualisatie Strategieën

Myocardial ischemia-reperfusion (I/R) injury remains a major determinant of outcome following acute myocardial infarction. Although timely reperfusion is essential for myocardial salvage, it simultaneously initiates inflammatory cascades that contribute to additional injury and drive long-term ventricular remodeling. Despite extensive experimental research, many cardioprotective strategies have failed to translate successfully into clinical practice, highlighting the need for a more nuanced understanding of the biological context in which I/R injury occurs. This thesis approaches myocardial I/R injury as a dynamic, inflammation-driven, and context-dependent process. Rather than focusing solely on infarct size as an endpoint, the work integrates mechanistic insights into innate immune signaling, evaluates cardioprotective strategies under conditions of increased inflammatory burden, and applies advanced in vivo imaging techniques to visualize myocardial injury and repair over time. Together, these approaches aim to help bridge the gap between experimental cardioprotection and clinical reality. A central finding of this work is that inflammation plays a critical role not only in acute myocardial injury but also in determining long-term ventricular remodeling. Studies targeting the immune receptor CLEC4E demonstrate that modulation of inflammatory signaling in cardiac resident cells significantly influences post-infarction remodeling and functional outcome, even when the extent of initial injury is comparable. These findings support the concept that adverse remodeling is not simply a passive consequence of infarct size, but an actively regulated process shaped by local immune responses within the myocardium. In parallel, explorative studies of cardioprotective interventions reveal that the efficacy of strategies such as ischemic postconditioning and colchicine is strongly influenced by baseline inflammatory state. While protective effects are preserved in young, healthy animals, these benefits are attenuated or altered in aged and obese animals. Importantly, differences between phenotypes emerge predominantly during the remodeling phase rather than being reflected in acute infarct size, underscoring the importance of incorporating comorbidities into preclinical models to improve translational relevance. A distinguishing methodological contribution of this thesis is the development and application of advanced imaging strategies to capture the temporal and spatial dynamics of myocardial I/R injury. The use of a newly developed remote, closed-chest ischemia model combined with manganese-enhanced magnetic resonance imaging enables real-time visualization of ischemic burden and myocardial viability, and demonstrates predictive value for long-term functional outcome. These findings highlight the role of imaging not merely as a diagnostic tool, but as a means to deepen mechanistic understanding and guide therapeutic evaluation. Taken together, this thesis emphasizes that myocardial I/R injury cannot be fully understood or effectively treated without considering inflammatory context, long-term remodeling processes, and the limitations of traditional experimental models. By integrating inflammation biology, cardioprotection research, and advanced visualization strategies, this work contributes a framework for future studies aimed at improving translational success in ischemic heart disease, particularly in patient populations characterized by chronic inflammatory burden.