Characterization of the spontaneous right ventricular hypertrophy and evolution to heart failure in Wistar Kyoto rat strain

Abstract

Heart failure is a pathological condition that remains as a major cause of morbi‐mortality in the world, and several cellular mechanisms involved in the development of heart failure remain unknown. In this study it was characterized a spontaneous experimental model of right ventricular hypertrophy from Wistar Kyoto rat strain and monocrotaline injection as a factor to induce the development of heart failure. Morphological and functional cardiovascular parameters, and atrial natriuretic factor (ANF) in serum were measured to determine criteria to be considered as a model of heart failure. Male WK rats 2 months old were assigned to 3 experimental groups (n=8 each group): control, right ventricular hypertrophy + saline (RVH+S) and right ventricular hypertrophy + monocrotaline (RVH+MCT). RVH was diagnosed through no invasive electrocardiographic record in awake animals, and one dose of monocrotaline (60 mg/Kg, ip) was injected. After 3 weeks, cardiovascular parameters were recorded (systemic and pulmonary systolic arterial blood pressure, heart rate), and arterial blood from aorta was taken and the heart was removed and analyzed. Total heart, right ventricle, left ventricle weights (g), and right ventricle free wall (in mm) were significantly different in the RVH+S (1.3±0.02, 0.40±14.11, 0.58±13, 2.86±0.19) and the RVH+MCT (1.6±0.09, 0.53±17.5, 0.67±18.94, 4±0.32) groups in comparison with the control group (0.99±0.04, 0.22±4.0, 0.55±14.38, 2.13±0.05), P>0.001 for all parameters, except for LV weight in the RVH+S group. The systemic arterial blood pressure analysis demonstrates absence of significant difference between groups, however, right ventricular pressure (RVP in mm Hg) in the RVH+S (42±2.53), and RVH+MCT (78±4.22), was significantly increased in comparison with the control group (22±1.16), P<0.001. ANF levels in serum were higher in the RVH+S and RVH+MCT experimental groups in comparison with the control group (537±11.04, 557±7.7 and 473±10.65 in pg/ml, respectively; P<0.01). The results suggest that a sub‐strain from WK rats develop right ventricular hypertrophy spontaneously and with the administration of monocrotaline, severe right and left ventricular hypertrophy was developed, changes associated to an increase in levels of atrial natriuretic peptide suggesting heart failure, then could be a useful experimental model of heart failure where right ventricular hypertrophy is a central pathologic mechanism.