| Objective:Heart failure is a group of syndromes which is defined as the abnormality of the cardiac structure or function leading to ventricular filling and (or) ejection ability damaged. Impaired cardiac output can not meet the damand of metabolism of the body. The main clinical manifestations are breathlessness, ankle swelling, and fatigue and so on. A data from the American Heart Association show during patients of heart failure who older than65years old, more than10%of them will develop into pulmonary hypertension and right heart failure. It has been suggested that the heart forms from two distinctly different cell populations that separate from a common progenitor. The differences in cardiac progenitor cell origin may contribute to the structural, functional, and geometric differences between the right and left heart. The mechanism of right heart failure study showed a role for right ventricular ischemia and maladaptive metabolic changes, specifically a switch from glucose oxidation to anaerobic glycolysis. Fatty acid oxidation (FAO) is the major source of ATP production (60-90%) in normal adult hearts, and uses12%more oxygen than GO to generate a given amount of ATP. Trimetazidine by activating pyruvate dehydrogenase or to inhibit endotoxin palmitic transport enzyme-1, thereby inhibiting the oxidation of free fatty acids, and secondarily promotes GO thereby reducing intracellular acidosis and preserving ATP levels. On the basis of above, this experiment aim to expore the impact of trimetazidine on the pulmonary hypertension induced right heart failure and myocardial metabolism.Methods:45Male New Zealand white rabbits were randomly divided into control group(CON)(15), right heart failure group(RHF)(15), trimetazidine treatment group(RHF+TMZ)(15), RHF group and RHF+TMZ group rabbits received a single intraperitoneal injection of monocrotaline (MCT, anhydrous ethanol with saline at1:5mixed dissolved,60mg/kg body weight), CON group were injected with an equivalent volume of saline. After four weeks of injection, the RHF+TMZ group were given trimetazidine20mg/kg(Saline gavage) for four weeks, RHF group and CON group were given the same amount of the narmal saline for4weeks. Changes in breathing rate, food intake, activities, spiritual, fur, weight, hydrothorax, ascites had been observed. Brain natriuretic peptide (BNP), serum adiponectin levels were measured after eight weeks of injection.Diameter of right ventricular, pulmonary artery pressure, and the left ventricular ejection fraction were measured by enchocardiography. Separated and calculated the right heart index(RV/(LV+S)), hepatic weight/body weight. Histological examination of right ventricular. High Performance Lipid Chromatography was used to estimated the ATP content of right ventricular myocardial.Results:1General situation, there was no death in CON group, no death in the RHF and RHF+TMZ group after4weeks of injection, RHF and RHF+TMZ group growthed slowerly than the CON group, decreased in food intake, poor spirit, less activity, hair thinning, dull, breathless and other performance. After injection of MCT,36days,42days,48days each death of a rabbit in the RHF group, while38days,50days each death of a rabbit in the RHF+TMZ group. The autopsy showed the right ventricular hypertrophy, hydrothorax and ascites. Remaining subjects were sacrificed after8weeks, there was no one of pleural and peritoneal effusions in the CON group, while in the RHF group there were11subjects with the performance of pleural and peritoneal effusions,10subjects in the RHF+TMZ group.2Comparison of the biomarker of heart failureThe level of serum BNP in CON group, RHF group, RHF+TMZ were (45.93±8.11) pg/ml、(188.33±16.10) pg/ml、(163.85±9.30) pg/ml respectively. Compared with the CON group, the levels of serum BNP in RHF and RHF+TMZ group were significantly higher (P<0.01). Compared with the RHF group, the level of BNP was significant lesser than in the RHF+TMZ group(P<0.01), the difference was statistically significant.The level of serum Adiponectin (APN) in CON group, RHF group, RHF+TMZ were(12.53±3.73)ug/ml、(38.67±3.28)ug/ml、(28.38±3.64)ug/ml respectively. Compared with the CON group,the levels of serum APN in RHF and RHF+TMZ group were significantly higher (P<0.01). Compared with the RHF group, the level of APN was significant lesser than in the RHF+TMZ group(P<0.01), the difference was statistically significant.3EchocardiographyThe diameter of right ventricular in CON group, RHF group, RHF+TMZ were (4.89±0.26) mm、(7.26±0.39)mm、(6.38±0.37) mm respectively. Compared with the CON group, the diameter of right ventricular in RHF and RHF+TMZ group were significantly higher (P<0.01).Compared with the RHF group, the diameter of right ventricular was significant lesser than in the RHF+TMZ group(P<0.01), the difference was statistically significant.The pulmonary artery pressure in RHF group, RHF+TMZ were(40.92±2.31)mmHg、(39.23±2.83)mmHg respectively. There was no statistically significant difference (P>0.05).The left ventricular ejection fraction in CON group, RHF group, RHF+TMZ were (68±4)%、(49±5)%、(53±3)%respectively. Compared with the CON group, the left ventricular ejection fraction in RHF and RHF+TMZ group were significantly lesser (P<0.01). Compared with the RHF group, the left ventricular ejection fraction was significant higher than in the RHF+TMZ group(P<0.01), the difference was statistically significant.4RV/(LV+S) and hepatic weight/body weightThe RV/(LV+S) in CON group, RHF group, RHF+TMZ were (25.07±2.12)%,(44.17±3.21)%,(37.54±2.60)%respectively. Compared with the CON group, the RV/(LV+S) in RHF and RHF+TMZ group were significantly higher (P<0.01). Compared with the RHF group, the RV/(LV+S) was significant lesser than in the RHF+TMZ group(<0.01), the difference was statistically significant. The hepatic weight/body weight in CON group, RHF group, RHF+TMZ were(26.87±1.88)g/kg、(36.75±2.01)g/kg、(33.08±2.50)g/kg respectively. Compared with the CON group, the hepatic weight/body weight in RHF and RHF+TMZ group were significantly higher (P<0.01). Compared with the RHF group, the hepatic weight/body weight was significant lesser than in the RHF+TMZ group(P<0.01), the difference was statistically significant.5Histological examination of right ventricularIn the CON group, cardiac muscle fibers arranged in neat rows, myocardium gap is normal; In the RHF+TMZ group thickening of the myocardial fibers arranged in disorder; In the RHF group, thickening myocardial fiber severely disorganized, muscle fibers have been broken.6Myocardial ATP contentThe myocardial ATP content in CON group, RHF group, RHF+TMZ were (3.17±0.14) umol/g、(1.51±0.25) umol/g、(2.05±0.27) umol/g respectively. Compared with the CON group,the myocardial ATP content in RHF and RHF+TMZ group were significantly lesser (P<0.01). Compared with the RHF group, the myocardial ATP content was significant higher than in the RHF+TMZ group(P<0.01), the difference was statistically significant.Conclusion:1After the intraperitoneal injection of monocrotaline, pulmonary artery hypertension induced right heart failure can be successful established. The decrease of ATP content in the RHF group suggecting the development of right heart failure is associated with the decline of oxygen utilization efficiency.2After the treatment of trimetazidine, the improvement of right heart failure symptoms and the increase of ATP content in the RHF+TMZ group suggecting that trimetazidine inhibit fatty acid oxidation, regulate the imbalances of myocardial fatty acid and oxidation of glucose, maintain the reserves of myocardial ATP energy, reduce the injury of myocardial hypoxia and the compensatory hypertrophy of right ventricle, thereby to improve the right heart function. |
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