While currently available therapeutic options for the treatment of acute myocardial infarction are sufficient for the treatment of symptoms, the underlying causes usually remain unresolved, being... Show moreWhile currently available therapeutic options for the treatment of acute myocardial infarction are sufficient for the treatment of symptoms, the underlying causes usually remain unresolved, being loss of electrically active, contractile, myocardial tissue. Recently, extensive research has been performed in the field of cell and gene therapy. The ultimate aim of these therapies is to __heal__ the infarcted area on a more biological basis, by repopulating the damaged area with __new__ cells that contribute to proper cardiac function, including electrical activation of the myocardium. In order to comprehend the potential therapeutic value and hazard of cell modification and transplantation for ischemic heart diseases, one should consider the heart as a highly integrative, electromechanical organ. Therefore, the aim of this thesis was to explore, from a mechanistic and electrophysiological point of view, the integrative and functional aspects of cell modification and transplantation as therapeutic options to cure the damaged, ischemic heart. Show less
In neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects... Show moreIn neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects of phenylephrine (chapter 2). Ventricular failure is associated with disturbed collagen turnover. Myocardial collagen turnover can be assessed by plasma PINP, PIIINP, and ICTP representing collagen synthesis (PINP, PIIINP) or degradation (ICTP). We investigated the effects of cardiac resynchronization therapy (CRT) on collagen turnover in patients at baseline and after 6 months of CRT (chapter 3). Monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and RV failure are associated with MMP activation in RV, we investigated whether NO plays role in RV hypertrophy and failure (chapter 4). In chapter 5 we reviewed novel approaches to treat experimental PAH. We investigated whether MCT-induced PAH and RV failure can be treated with mesenchymal stem cells (MSCs) from donor rats with PAH caused by MCT. At day 14 after MCT, recipient rats were treated with MSCs. In chapters 6,7 the effects of MSCs on pulmonary pathology and RV function were examined. Isolated cardiomyocytes were investigated for PAH-related changes in excitability. In chapter 8 we reported on excitability properties dependent on Kv-channel expression, proposed to play a role in arrhythmias. Show less
