Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Pharmacology

Background: Despite advances in the management of heart failure, the prognosis of these patients remains poor. The results of the randomized clinical trials in patients with DHF (or HFPEF) have demonstrated that while neurohumoral antagonists such as beta blockers, angiotensin converting enzyme inhibitors and angiotensin II receptor blockers are effective in treatment of systolic heart failure (SHF), they do not decrease morbidity and mortality in DHF (Redfield et al., 2003). Development of new forms of interventions remains a challenging task (Lloyd-Jones et al., 2010). Aim: The aim of this work is assessment of lusitropic effect of phosphodiesterase -5 inhibitors (sildenafil) and EPO in a model of diastolic heart failure in female albino rats induced by NG-nitro-L-arginine methyl ester (L-NAME). In addition, to assess the effect of the aforementioned drugs on left ventricle haemodynamic parameters and left ventricular remodeling. Results: In the present study treatment with L-NAME revealed, significant reduction in the mean LVEF and LVFS compared to that recorded in normal group . While milrinone, sildenafil, erythropoietin and combination treatment treated groups showed significant increase in the mean LVEF and LVFS compared to that recorded in L-NAME treated group. Regards ECG records, QT interval prolonged with L-NAME administration compared to that recorded in normal group. While treatment with milrinone , sildenafil and combination treatment showed significant shortening of QT interval compare to that recorded in L-NAME treated group. On the other hand , erythropoietin reduction of QT interval was non-significant compare to that recorded in L-NAME treatment

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