ABSTRACT
BACKGROUND:Erythropoietin and bone marrow mesenchymal stem cells have been shown to affect myocardial apoptosis. However, few studies concerned their combined application to sepsis-related myocardial injury. OBJECTIVE:To observe the effects of the combination of erythropoietin and bone marrow mesenchymal stem cells on pathology and apoptosis of sepsis rat cardiomyocytes. METHODS:A total of 50 Sprague-Dawley rats were randomly selected and assigned to five groups (n=10). Sepsis models were established by cecal ligation perforation method. Rat models in the bone marrow mesenchymal stem cellgroup, erythropoietin group and erythropoietin+bone marrow mesenchymal stem cellgroup were respectively treated with bone marrow mesenchymal stem cells, erythropoietin and erythropoietin+bone marrow mesenchymal stem cells immediately after model induction via intraperitoneal injection or caudal vein. Model group received cecum ligation and puncture. Control group did not undergo any treatment after the abdomen was opened. Model and control groups were infused with an equal volume of physiological saline via caudal vein. At 24 hours, experimental animals were sacrificed by anesthesia. Myocardial specimens were col ected. Myocardial appearance was observed using hematoxylin-eosin staining. Bax, Caspase-3 and Bcl-2 were tested by western blot assay. RESULTS AND CONCLUSION:Hematoxylin-eosin staining:cardiomyocytes were regularly arranged, showing integrated structure in the control group. Extensive myocardial fiber breakage, disordered arrangement, cardiomyocyte swel ing or shrinkage, and vacuolar degeneration were observed in the model group. Moreover, myocardial interstitial vascular congestion, edema, and inflammatory cellinfiltration were visible. Myocardial tissue was similar between erythropoietin and bone marrow mesenchymal stem cellgroups, with the presence of mild inflammatory cellinfiltration and scattered normal cardiomyocytes. In the erythropoietin+bone marrow mesenchymal stem cellgroup, cardiomyocytes were slightly damaged. Interstitial vascular congestion was not apparent, and a few inflammatory cells infiltrated. Western blot assay results demonstrated that Bcl-2 protein expression was significantly higher (P<0.01), but Bax and Caspase-3 protein expression was lower (P<0.05) in the erythropoietin+bone marrow mesenchymal stem cellgroup than in the erythropoietin, model and control groups. The combination of erythropoietin and bone marrow mesenchymal stem cells in treatment of sepsis-related myocardial injury could lessen myocardial pathological changes, and inhibit cardiomyocyte apoptosis. The mechanisms maybe exert by upregulating anti-apoptotic protein expression and downregulating apoptotic protein expression.
ABSTRACT
Objective To prospectively evaluate the safety and therapeutic efficacy ofdalteparin in patients with high risk non-ST-elevation acute coronary syndromes (ACS) during percutaneous coronary intervention (PCI). Methods Atotal of 175 patients with high risk non-ST-elevation ACS were randomly assigned to 2 groups [dalteparin group and unfractionated heparin (UFH) group]. The patients in dalteparin group were given dalteparin at a dose of 5,000U subcutaneously soon after diagnosis and then an additional 60U/ kg intravenous bolus ofdalteparin before emergent PCI. Vascular access sheaths were removed immediately after PCI or coronary artery angiography; the patients in UFH group were given UFH intravenously at a dose of 25mgjust before PCI and an additional 65mg bolus was administered if angiographic findings showed that the patients were suitable for percutaneous transluminai coronary angioplasty (PTCA). Sheaths were removed at 4-6 hours after PCI; Results Eighty-three patients in dalteparin group underwent PCI while 82 patients in UFH group underwent PCI; anti-Xa activities of 52 patients in dalteparin group were measured. The average anti-Xa activity was (0.83±0.26) U/ml at 15 minutes after intravenous injection of dalteparin and anti-Xa>0.5U/ml was obtained in 96.1% of the patients; hematomas at puncture sites were significantly fewer in dalteparin group as compared with UFH group (2.3% vs 9. 2%, P < 0.05); none of the patients in 2 groups suffered major bleeding events. No death, acute arterial reocclusion or emergent revascularization events occurred at 30 days after PCI. Conclusions Our study demonstrated that early subcutaneous injection of dalteparin at a dose 5,000U after diagnosis and an additional 60U/kg intravenous bolus ofdalteparin before PCI is safe and efficacious for patients with high risk non-ST-elevation ACS undergoing emergent PCI