Experimental Myocardial Infarction: The quest for novel therapeutics

Abstract

Myocardial infarction (MI) and its consequences are associated with high mortality rates and considerable health care costs. Novel therapeutics that protect the heart after MI are therefore required. To assess safety and efficacy before exposing patients to experimental compounds, thorough preclinical testing in representative translational animals is required. However, successful clinical implementation of cardioprotective compounds has not yet been established, while many animal studies have been found positive. This implies that experimental study design is not representative for clinical practice. The quest for novel therapeutics for patients suffering from MI should therefore not only focus on a continued search for novel compounds to treat MI patients, but also focus on improving experimental MI study protocols and functional read-outs to increase the translational value of large animal experimental MI studies. Accordingly, the aim of this thesis is to (1) optimize large animal model study protocols, (2) to validate new measurements that reflect cardiac function and (3) continue the search for therapeutic strategies that attenuate ischemia-reperfusion injury or prevent adverse remodeling in patients post-MI.