The monocrotaline (MCT) rat model of pulmonary artery hypertension has enabled the investigation of electrical and mechanical remodelling that occurs in the right ventricle in response to chronic increases in chamber volume or wall stress that occurs in this disease state. We used Microarray Card Technology by Applied Biosystems and predictive computer modelling to assess whether changes in gene expression were consistent with alterations in electrical activity. Male Wistar rats were injected with 60 mg/kg of MCT (n=14) or an equivalent volume of saline (CON, n=12). Heart failure develops within 4 weeks following injection. On the presentation of clinical symptoms of heart failure, rats were killed by schedule 1 procedures, hearts removed and dissected into right ventricular (RV) and left ventricular (LV) portions. Tissue samples from these regions were analysed using real-time reverse transcription polymerase chain reaction to measure the mRNA expression ratio of a range of genes relative to the housekeeper gene 18S. Changes in gene expression were used to scale ion channel conductances (Chandler et al. 2009) in the rat ventricular myocyte computer model of Pandit et al. (2001) to predict the effect of changes in expression on action potential configuration. MCT treated rats had increased heart weight: body weight (CON 4.1 ± 0.2 vs. MCT 5.7 ± 0.2 mg/g) and RV weight:LV weight (CON 0.36 ± 0.02 vs. MCT 0.73 ± 0.07 g/g), consistent with the development of right ventricular hypertrophy/failure (t-test P<0.001, mean ± SEM). We observed statistically significant increased expression in gene markers for heart failure in the RV of MCT treated animals, e.g. A and B type naturietic peptides, collagen type 1 and beta-myosin heavy chain (2-way ANOVA P<0.001). However there was a statistically significant decrease in the expression of a range of potassium channel genes including those encoding for channels responsible for Ito (Kv1.4, Kv4.2, Kv4.3) IKr (Kv11.1), IKs (Kv7.1) and IK1 (Kir2.1) in RV MCT animals (e.g. Kv 4.2 expression was CON 0.96 ± 0.05 vs. MCT 0.18 ± 0.06, 2-way ANOVA P<0.001). Modelling predicted that these changes in gene expression, if linearly scaled to channel conductance, would increase the action potential duration at 90% repolarisation from 32 ms to 70 ms. We have previously reported prolongation of the in vivo ECG, QT interval and the monophasic action potential of isolated hearts (Stones et al. 2009, Benoist et al. 2009). Thus we conclude that MCT treatment results in changes in gene expression consistent with observed changes in electrical activity, which may increase the arrhythmic susceptibility in this disease state.