mercaptopurine and Heart-Failure

Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB).. Male Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses.. PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats.. Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.

Topics: Animals; Apoptosis; Blood Pressure; Disease Models, Animal; Heart Failure; Heart Ventricles; Hemodynamics; Hypertension, Pulmonary; Male; Mercaptopurine; Rats, Wistar; Ventricular Function, Right; Ventricular Remodeling

Topics: Anti-Inflammatory Agents, Non-Steroidal; Atrial Fibrillation; Azathioprine; Cardiac Imaging Techniques; Colitis, Ulcerative; Fever; Heart Failure; Humans; Hypotension; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Mercaptopurine; Mesalamine; Middle Aged; Myocarditis

Topics: Adult; Aged; Amsacrine; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Cytarabine; Daunorubicin; Female; Heart; Heart Failure; Humans; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Tretinoin

Topics: Aged; Anemia, Hemolytic, Autoimmune; Antibodies; Cellulose; Chromatography; Complement System Proteins; Female; Heart Failure; Hemagglutination Tests; Hematocrit; Hemoglobinuria; Hemolysin Proteins; Humans; Mercaptopurine; Methicillin; Myocardial Infarction; Pneumonia; Prednisolone

Topics: Child; Diagnosis; Electrocardiography; Heart; Heart Failure; Humans; Leukemia; Mercaptopurine; Methyltestosterone; Pathology; Prednisone; Radiography, Thoracic; Radiotherapy