Effects Of Simvastatin, Autologous Bone-Marrow Mononuclear Cells Transplantation And Their Combination On Treating Myocardial Infarction In Rabbits

Objective: To compare effects of autologous bone-marrow mononuclear cells transplantation, simvastatin and their combination on heart function and vascular proliferation after acute myocardial infaction in rabbits.Methods: 1. Experimental objective: New Zealand rabbits, male, 2.0 to 2.5kg in body weight. 2. Experimental groups: 32 rabbits were randomly divided into four groups(n=8). GroupⅠwas control group, groupⅡwas simvastatin-treated group, groupⅢwas autologous bone-marrow mononuclear cells transplantation group and groupⅣwas simvastatin-treated + autologous bone-marrow mononuclear cells transplantation group.Control group and simvastatin-treated group were myocardial infarction group.Myocardial infarction was induced by ligating ramus circumflexus arteriae coronariae sinistrae in all rabbits. Autologous bone-marrow mononuclear cells transplantation treated rabbits of groupⅢand groupⅣafter AMI. All rabbits began to take foods on the first day after operation. Simvastatin (5mg.kg-1.d-1) was administered daily to the rabbits of groupⅡand groupⅣ,and placebo was administered to the rabbits of groupⅠand groupⅢ. All rabbits were sacrificed after 4 weeks to get the heart to make pathological section.3 Detective parameters:①Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were measured by echocardiography before operation and at the end of the fourth week after operation,and then left ventricular ejection (LVEF) was counted.②t he size of infracted myocardium by HE stain.③The counts of microvessel on the margin of the infarcted myocardium were evaluated by immunohistochemistry.Results: 1. LVEF of groupⅠ, groupⅡ,groupⅢand groupⅣwere 71.32±3.58%, 70.28±3.54%, 71.24±3.57%, 70.36±3.52% respectively before operation. There was no significant difference among them. At the end of the first week after operation, LVEF of groupⅠ,groupⅡ,groupⅢand groupⅣwere 47.54±3.23%,48.74±3.25%,49.32±3.34%,50.42±3.27%. LVEF decreased significantly at the end of the first week after operation among these four groups. At the end of the fourth week after operation, LVEF of groupⅠ, groupⅡ, groupⅢand groupⅣwere 45.64±3.58%,55.34±2.56%,57.28±3.12%,67.66±3.52% respectively.Compared with groupⅠ, LVEF were significantly improved in other groups,especially in groupⅣ. 2. HE stain showed that the sizes of infracted myocardium of groupⅠ,groupⅡ, groupⅢand groupⅣwere 42.64±5.94% , 37.45±5.36% ,35.18±4.98% , 27.36±4.12% respectively.Compared with groupⅠ,the sizes of infracted myocardium were significantly decreased in other groups ,especially in groupⅣ. 3. The capillary density of groupⅠ,groupⅡ,groupⅢand groupⅣassessed by immunohistochemical staining with polyclonal antibodies against FactorⅧ-related antigen were 12.1±3.2,18.2±3.8, 19.1±3.9,28.4±4.3 respec- tively. Compared with groupⅠ, the capillary density of infracted myocardium were significantly increased in other groups , especially in groupⅣ.Conclusion: Autologous bone-marrow mononuclear cells transplantation,simvastatin and their combination all can promote vascular proliferation and decrease MI size after myocardial infarction, improve left ventricular function, with their combination superior.