Effects of Recombinant Human Erythropoietin on the Cardiac Function and Infarct Size after Myocardial Infarction in Rats / 昆明医科大学学报

ABSTRACT

Objective Ventricular remodeling mode after myocardial infarction in rats was used to investigate the effects of recombinant human erythropoietin (rHu-EPO) on hemodynamic,ventricular function and infarct size of left ventricle in rats with myocardial infarction, so as to find out the optimum time and protocol of EPO treatment for ventricular remodeling after myocardial infarction and provide evidence for clinical application of EPO. Methods Sixty healthy male Sprague Dawley rats were divided randomly and equally into 5 groupssham group,simple cardiac remodeling after myocardial infarction group, the intervention groups of different drugs ( rHu-EPO in the intervention group and SB203580 group,rHu-EPO+SB203580,group) . Ligation was set at more than 1/3 points on the anterior descending coronary artery to make model of myocardial infarction in rats, and the rats were feeded for four weeks. Different drugs in the intervention groups were subcutaneously injected once before ischemia and twice a week after ischemia. Respectively, 24 hours, 2 weeks, and 4 weeks after ischemia, we detected the hemodynamic parameters, recorded the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure (+dp/dt) and left ventricular pressure decline rate (-dp/dt), and recorded the synchronization of heart rate (HR) . The animals were sacrificed 4 weeks after ischemia, and the heart specimens were collected. The relative weight of left and right ventricle (LV/BW in the RV/BW) was calculated according to the left and right ventricular weight (LVW, RVW) . TTC and Evans blue staining was used to detect left ventricular infarct size, and pathological examination was used to observe the gross and microscopic morphological change. Results 24 hours after operation Compared with the sham group, in simply cardiac remodeling after myocardial infarction group, rats' left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and left ventricular pressure maximum rise and fall rate (±dp/dt) was significantly abnormal,LVSP and ± dp/dt were significantly reduced, the LVEDP was significantly increased (P<0.05);compared with simply cardiac remodeling after myocardial infarction group, in the intervention groups (rHu-EPO in the intervention group, SB203580 group, rHu-the EPO + SB203580 group) rats' ± the dp /dt improved significantly (P<0.05) . After 2 weekscompared with the sham group, in simple cardiac remodeling after myocardial infarction group rats’LVSP and LVEDP and ± dp/dt significant deterioration (P<0.05) ;compared with simply cardiac remodeling after myocardial infarction group, in the intervention group (rHu-EPO in the intervention group, SB203580 group, rHu-the EPO+SB203580 group) rats’± the dp/dt was significantly improved (P<0.05) . After 4 weekscompared with the sham group, in simple cardiac remodeling after myocardial infarction group rats’LVSP and LVEDP and ± dp/dt significant deterioration (P<0.05) ; compared with simply cardiac remodeling after myocardial infarction group, in the intervention groups (rHu-EPO in the intervention group, SB203580 group, rHu-the EPO + SB203580 group) rats' ± the dp/dt was significantly improved (P<0.05) . Compared with the sham group, in simply cardiac remodeling after myocardial infarction group rats' LV/BW increased, the difference was statistically significant (P<0.05) . Compared with simply cardiac remodeling after myocardial infarction group,in the intervention group (rHu-EPO in the intervention group and SB203580 group, rHu-the EPO+SB203580 group) rats’LV/BW decreased, the difference was statistically significant (P<0.05 ) . Compared with simply after myocardial infarction cardiac remodeling group, in the intervention groups (rHu-EPO in the intervention group and SB203580 group,rHu-EPO+SB203580 group) rats’cardiac infarct size was significantly reduced (P<0.05). Conclusions rH-EPO can protect the heart function through improving the left ventricular systolic and diastolic function after AMI in rats.RH-EPO can suppress ventricular remodeling, through reducing ventricular relative weight and infarct size and promoting the renewal of capillary in infarction area after AMI in rats.