EFFECT OF PINACIDIL ON MYOCARDIAL REMODELING IN PRESSURE OVERLOAD HEART FAILURE RAT MODEL: PP.1.28

Abstract

Objective: To investigate the effect of pinacidil on heart function and myocardial remodeling in pressure overload heart failure rat model. Methods: Chronic overload heart failure model was established by abdominal aortic constriction. 40 male Wistar rats were randomized into 3 groups: sham-operated group (F), aortic-banded group (T) and Pinacidil group (M). Rats in M group received Pinacidil 2 mg/kg/day at the 4th week after operation. Hemodynamic parameters such as left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were recorded at the 12th week after operation. Serum BNP levels, collagen type I and aminotermianl peptide of type ¢óprocollagen were tested by ELISA kit. After the rats were killed, the mass indexes of hearts(MI) were calculated (organ mass/body weight). Myocardial fibre diameters were measured after HE stain. Results: (1) Compared with the sham-operated group, in aortic-banded group the heart MI were increased dramatically[T£4.0±0.3£©vs F£2.7±0.1£©g/kg£ p < 0.01], the myocardial fibre diameters were increased either[T£19.26±2.25£©vs F£17.32±1.43£©¦Ìm£ p < 0.01]. Pinacidil markedly decreased the above two indexes[MI: M£3.5±0.4£©vs T£4.0±0.3£©g/kg£ p < 0.01£»Myocardial fibre diameter: M£17.3±1.4£©vs T£19.26±2.25£©¦Ìm£ p < 0.05].£2£©LVEDP was higher in T group than F group£¬and was lower in M group. Serum BNP levels increased significantly in T group[T£475.5±1.1£©vsF£171.1±49.1£©pg/ml£ p < 0.01]. Even though Pinacidil dramatically decreased the BNP level[M£353.7±7.8£©vs T£475.5±1.1£©pg/ml£ p < 0.05]£ it still higher than F group£p < 0.01£©. (3)The serum levels of collagen type I [T£5.5±1.8£©vs F£3.4±0.2£©g/ml£ p < 0.01]and P¢óP [T£570.7±165.5£©vs F£339.7±93.4£©pmol/L£ p < 0.01]were both increased significantly in T group as compared with F group (p < 0.05). Pinacidil dramatically decrease the above two parameters£p < 0.01£©. Conclusions: Pinacidil can improve the myocardial hypertrophy and fibrosis after abdominal aortic constriction, and delay the progression of heart failure.