Early inflammatory response during the development of right ventricular heart failure in a rat model

• Published in: European journal of heart failure Vol. 12; no. 7; pp. 653 - 658
• Main Authors: Campian, Maria E., Hardziyenka, Maxim, de Bruin, Kora, van Eck-Smit, Berthe L.F., de Bakker, Jacques M.T., Verberne, Hein J., Tan, Hanno L.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.07.2010
• Subjects: 67Ga; Animals; Autoradiography; Disease Models, Animal; Disease Progression; Gallium Radioisotopes; Gene Expression Profiling; Heart failure; Heart Failure - blood; Heart Failure - chemically induced; Heart Failure - physiopathology; Hypertrophy, Right Ventricular - blood; Immunochemistry; Inflammation; Inflammation - etiology; Male; Monocrotaline - adverse effects; Myeloperoxidase; Myocardium - metabolism; Neutrophil Activation - physiology; Peroxidase - metabolism; Radionuclide Imaging; Rats; Rats, Wistar; Right ventricle; Scintigraphy; TNF-α; Tumor Necrosis Factor-alpha - analysis; Ventricular Dysfunction, Right - blood; Ventricular Dysfunction, Right - complications; Ventricular Dysfunction, Right - diagnostic imaging
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1093/eurjhf/hfq066

Aims Inflammatory activation plays an important role in the pathogenesis and progression of left ventricular (LV) heart failure. In right ventricular (RV) heart failure, little is known about the role of inflammatory activation. We aimed to study the role of inflammatory activation in RV heart failure by serial monitoring during disease progression. Methods and results Right ventricular heart failure was induced in male Wistar rats by intraperitoneal injection of monocrotaline (MCT). Two groups were studied: MCT‐treated rats (MCT‐rats), and age‐matched controls (CON‐rats). Serial echocardiography and in vivo 67‐Gallium (67Ga) scintigraphy were performed. Local inflammation in the RV was assessed by (i) ex vivo semi‐quantitative 67Ga autoradiography, (ii) immunohistochemistry of myeloperoxidase (MPO), a marker of neutrophil activity, and (iii) mRNA assays of tumour necrosis factor‐alpha (TNF‐α). In MCT‐rats, 67Ga scintigraphy showed increased myocardial uptake which started during the early stages of RV disease. 67Ga autoradiography revealed that this increased 67Ga uptake occurred in the RV and inter‐ventricular septum, but not in the LV. The stage‐dependent increases of in vivo 67Ga RV myocardial uptake were paralleled by increases in mRNA gene expression for TNF‐α in RV, and increased MPO staining in RV. Conclusion Development and progression of RV heart failure is associated with an early increase in RV inflammation. 67Ga scintigraphy may be used for the serial assessment of inflammation and monitoring of disease progression in RV heart failure.