In view of the increasing rate of heart failure (HF) cases, this disease is subject to intensive research, both experimental and clinical. HF is divided into heart failure with reduced ejection fraction (HFrEF) caused most often by myocardial infarction, and that with preserved ejection fraction (HFpEF), for which the predisposing factors include advanced age and such civilisational diseases as hypertension, diabetes and obesity. Typical symptoms of both HFpEF and HFrEF are fatigue, dyspnoea and oedemas. Regardless of the ejection fraction, patients with the most severe form of heart failure, i.e. NYHA IV, are in the group in which the annual mortality rate is as high as 40%. The description of nitrosative stress in cardiomyocytes has become a breakthrough discovery in understanding of the HFpEF pathomechanism. It was proven that apart from HFpEF, increased level of iNOS also occurs after myocardial infarction leading to HFrEF, or after long-term application of high-fat diet leading to metabolic syndrome, which predispose patients to HFpEF. The first stage of our project consisted in conducting an experiment on rats which were divided into 4 groups, depending on the procedure conducted. From the 4th week of life, half of the rats were fed with high-fat diet (it contributed to the development of obesity and metabolic syndrome which is a significant risk factor for the occurrence of heart failure with preserved ejection fraction), and the other half was fed with standard diet. In the 8th week of life, coronary artery ligation surgeries were conducted (leading to post-infarction heart failure) or simulated operations. In the 12th week of life, left ventricle muscles were taken from all individuals and then frozen for future laboratory analyses. The second stage of the project assumes inclusion to the study two groups of 40 patients with diagnosed, respectively, HFpEF or HFrEF. The patients will be assessed in terms of co-existence of diabetes, hypertension and obesity; they will have marked the basic laboratory parameters (lipid profile, HBA1C) and echocardiography made with the analysis of the ejected fraction and left ventricular diastolic function. Apart from that, blood will be taken from the patients, which will be transported to the Centre for Pre-clinical Research and Technology (CePT) in order that assays are made with ELISA method.
dr n. med. Małgorzata Wojciechowska
W ramach projektu przewidziano następujące zadania