The inflammatory response in myocarditis and acute myocardial infarction

This thesis is about myocarditis and acute myocardial infarction (AMI). These are two cardiac diseases in which inflammation of the cardiac muscle occurs. In myocarditis, inflammation results in the elimination of a viral infection of the heart. During AMI, one of the coronary arteries is occluded, causing ischemia and damaged cardiac muscle cells. Here, inflammation removes these damaged cells, so that scar formation can occur. However, for both diseases, inflammation also results in additional damage to the heart, actively increasing morbidity and mortality related to myocarditis or AMI. Therefore, it is important to be able to diagnose and treat inflammation of the heart adequately. The projects described in this thesis contribute to this purpose. First, we investigated a new diagnostic method for myocarditis, and found that by quantifying leukocytes in a quadriceps muscle section, we can diagnose myocarditis with great accuracy. We also demonstrated that atrial inflammation occurs in myocarditis patients, and we investigated the efficacy of an anti-inflammatory drug (colchicine) in a mouse model of acute viral myocarditis. For AMI, we investigated another anti-inflammatory drug (C1-inhibitor). First, we evaluated two different administration routes for C1-inhibitor in rats (subcutaneous and intravenous administration). Next, we induced AMI surgically in rats, and demonstrated herein that C1-inhibitor can reduce atrial inflammation. Finally, in the same rat model we investigated a stem cell therapy, and found that stem cell administration after AMI restores the cardiac function of the rats.