Thesis Reindert Emmens

On 5 July 2016 Reindert Emmens defended his thesis ‘The inflammatory response in myocarditis and acute myocardial infarction’ at the University of Amsterdam.

Promotores: Prof SM van Ham PhD and prof JWM Niessen
Co-promotores: PAJ Krijnen PhD and D Wouters PhD

Summary

This thesis focusses on two cardiac diseases where inflammation plays an important role in the pathogenesis: myocarditis and acute myocardial infarction (AMI). 

Myocarditis is a heterogeneous disease, which makes it difficult to diagnose and treat. We first determined the diagnostic efficacy of lymphocytic infiltration of quadriceps muscle biopsies of myocarditis patients post-mortem. Next, we investigated the potential therapeutic efficacy of the anti-inflammatory drug colchicine in mice with acute coxsackievirus-induced myocarditis. Unfortunately, we found that colchicine caused severe pancreatic damage in these mice. Finally, we found that myocarditis patients also have inflammation in the atria, which may predispose these patients towards the development of atrial fibrillation.

The complement system plays in important role in the inflammatory response in the heart following AMI. Therapeutic inhibition of complement has been studied extensively in AMI animal models and AMI clinical trials. For one of these therapeutics, namely C1-inhibitor, we first investigated several administration routes in rats and compared C1-inhibitor plasma levels in time. Following this, we administered C1-inhibitor to rats with experimentally induced AMI, and found that C1-inhibitor does not only inhibit inflammation in the ventricles, but also in the atria of the heart. In addition, we found that C1-inhibitor is also produced locally in the heart following AMI. Finally, we compared in rats with experimentally induced AMI two time points of adipose-derived stem cell administration, and investigated the effects on infarct size reduction, improvement of cardiac function and on cardiac inflammation.