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

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. 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 ((67)Ga) scintigraphy were performed. Local inflammation in the RV was assessed by (i) ex vivo semi-quantitative (67)Ga autoradiography, (ii) immunohistochemistry of myeloperoxidase (MPO), a marker of neutrophil activity, and (iii) mRNA assays of tumour necrosis factor-alpha (TNF-alpha). In MCT-rats, (67)Ga scintigraphy showed increased myocardial uptake which started during the early stages of RV disease. (67)Ga autoradiography revealed that this increased (67)Ga uptake occurred in the RV and inter-ventricular septum, but not in the LV. The stage-dependent increases of in vivo (67)Ga RV myocardial uptake were paralleled by increases in mRNA gene expression for TNF-alpha in RV, and increased MPO staining in RV. Development and progression of RV heart failure is associated with an early increase in RV inflammation. (67)Ga scintigraphy may be used for the serial assessment of inflammation and monitoring of disease progression in RV heart failure.