Studying the impact of modulated inflammation in cardiac ischemia reperfusion injury.

Ischemic heart disease is a leading cause of death. The metabolic, functional and structural changes after acute myocardial injury, also termed cardiac remodelling, determine residual cardiac function, development of heart failure and survival. Inflammation and reperfusion not only contribute to infarct healing but paradoxically can also cause aggravation of the injury (metaflammation). Ischemic postconditioning has shown its beneficial role in infarct size reduction and cardiac remodelling in rodent models. In rodent models with comorbidities (= pro-inflammatory state) it seemed a higher threshold was present before activating thess endogenous cardioprotective pathway. To study the relationship between inflammation and remodeling, we will use preclinical senile rodent models and rodent models with metabolic syndrome (DKO for leptin & LDL-R), pharmacological intervention (colchicine) and surgical intervention (ischemic postconditioning). To establish the acute myocardial ischemia and perform postconditioning during imaging a technical-surgical procedure will be developed. Using advanced state-of-the art imaging infrastructure (PET-MRI), we will be able to perform longitudinal monitoring of cardiac function, metabolism and inflammation to describe the process of cardiac remodeling after an acute ischemic injury and different interventions in individual models. It is our goal to identify the role of inflammation in cardiac remodelling and explore its therapeutic options.