Protection Against Myocardial Ischemia and Reperfusion: Preconditioning, postconditioning and hibernation
Preconditioning, postconditioning and hibernation
Ischemic heart disease is currently the leading cause of morbidity and mortality in the industrialized world and is expected to become the leading cause of death world wide by the year 2020 when it will surpass infectious diseases.1, 2 In 2006 42,522 people died of cardiovascular disease (CVD) in the Netherlands. This translates into an average of 116 people per day that die due to CVD. When looking at all cause mortality one in every three persons dies due to CVD. Ischemic heart disease is the main component of this group with 12,491 deaths, while 9,976 deaths are due to cerebrovascular disease. Together they are responsible for 52% of the deaths in CVD. Around 70% of the people with ischemic heart disease die due to an acute myocardial infarction (AMI).3 The impact of CVD on health care is refl ected by the number of invasive interventions: the number of percutaneous coronary interventions (PCI) is still increasing (33,678 in 2006), while the number of open heart surgeries (coronary artery bypass grafting or CABG) is stable over the past 5 years (around 15,000).3 After myocardial infarction, the surviving myocardium undergoes a complex sequence of cardiac remodeling, which may have a benefi cial eff ect on cardiovascular performance in the short-term, but which become detrimental in the long-term and ultimately causes heart failure. In experimental studies, the degree of deleterious remodeling is highly aff ected by the size of the infarct.4 Accordingly, clinical reports indicate that infarct size estimated by peak plasma creatine kinase activity is an independent predictor of left ventricular remodeling and the subsequent development and severity of heart failure.5 In view of the important role myocardial infarct size plays in the etiology of heart failure, limiting infarct size is an important strategy to reduce the incidence and severity of heart failure. Furthermore, infarct limitation is an important therapeutic goal since it is also related to other factors such as severity of ventricular arrhythmias, mortality and loss of productivity. Hence, it is of utmost importance to salvage as much myocardium as possible by initiating reperfusion as rapidly as possible, either by PCI or CABG, in addition to other therapeutic strategies that target the remodeling process (e.g. angiotensin converting enzyme inhibitors).6 This thesis will mainly focus on some of the mechanisms involved in adaptation to ischemia and reperfusion in the myocardium in order to minimize cell death and hence limit infarct size.
|Keywords||coronary diseases, epidemiology, heart diseases, ischemic heart disease, reperfusion|
|Promotor||D.J.G.M. Duncker (Dirk) , J.M.J. Lamers (Jos)|
|Publisher||Erasmus MC: University Medical Center Rotterdam|
Manintveld, O.C.. (2008, October 8). Protection Against Myocardial Ischemia and Reperfusion: Preconditioning, postconditioning and hibernation. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/16433