StatusThe thesis was presented on the 10 June, 2008
Approved by NCAA on the 18 September, 2008
Abstract– 0.36 Mb / in romanian
0.75 Mb /
This study focused on the evaluation of cardioprotecting effects of pravastatin in patients receiving cardiotoxic anthracycline-containing chemotherapy and in experimental rats models of doxorubicin-induced cardiomyopathy. The results of the present study showed significant disturbances in diastolic and systolic functions of isolated heart, occurred in doxorubicin-treated rats. Simultaneous pravastatin administration resulted in successful preservation of cardiac indexes.
ECG, EchoCG, plasmatic CK-MB activity, blood lipid concentration and chemotherapeutic efficacy in 78 patients with Non-Hodgkin′s lymphoma, treated during 6 months in accordance with CHOP regimen, were carried out. Within the groups without statin administration there were determined typical doxorubicin-induced changes in the cardiac functional indexes. Diastolic dysfunction was developed in ¼ of patients with low risk of cardiac complications (control group). Within the 2nd group (with important cardiovascular risk) were estimated diastolic disturbances progression and left ventricular contractility deterioration. Significant increment in MPI denoted an aggravation. Important melioration of cardiac activity was observed within the 3rd group (with important cardiovascular risk and simultaneous 20 mg/day pravastatin administration): increase in ejection fraction and ejection time, decrease of MPI, twice reduction of diastolic disturbances cases.
Prolonged QT interval due to doxorubicin-containing chemotherapy was found out in both groups without statin co-medication. Number of patients with a pathological interval underwent a twice rise into 2nd group. Within the group receiving pravastatin QTc shortening and interval normalization occurred in ⅔ patients with previous QT abnormalities.
An eloquent increment in plasmatic CK-MB activity was identified in control group after 3 month follow up and after 6 month – into 2nd group. Within the 3rd group a similar dynamic was prevented with pravastatin.
Aggravation or development of cardiovascular pathology was a clinical evidence of anthracycline cardiotoxicity and was estimated in 42,9% of 2nd group patients. Thus, heart failure functional class rose in 31,4% cases. Contrarily, statin co-medication acted upon previous cardiovascular pathology melioration in 21,4% cases. Its hypocholesterolemic effect resulted in significant decrease of total cardiovascular risk in 36% patients of 3rd group. Evaluation of statin influence on chemotherapeutic efficacy did not discover some meaningful evidences.
Considering many recent researches, statin-determined cardiac function melioration in different cardiovascular pathologies was noted. The obtained effectualness is probable based on the pleiotropic actions of statins: antioxidant, antiinflammatory, immunomodulatory, endothelial protection etc., wich are summarized and ensure the cardioprotecting effect of pravastatin in anthracycline-induced cardiotoxicity.
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