ABSTRACT
Objective@#To investigate the early intervention effects of metoprolol on connexin 43(Cx43) and phosphorylated Cx43 (p-Cx43) expression in rabbits with post myocardial infarction.@*Methods@#A total of 24 adult male New Zealand white rabbits were divided into sham group (n=6), early treatment group(n=6), routine treatment group(n=6), and myocardial infarction group(n=6) with a randomized block design blocked by weight. Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation. Rabbits in sham group received similar surgical procedure without LAD ligation. Metoprolol (12.5 mg/kg dissolved in 2 ml distilled water) was applied to rabbits in early treatment group and routine treatment group per gavage immediately after recovery from anesthesia and at 24 hours after myocardial infarction, respectively, then treated daily for 40 days. Rabbits in sham group and myocardial infarction group received 2 ml distilled water per gavage daily for 40 days. Plasma lactate dehydrogenase (LDH) and creatine kinase (CK) level were detected by automatic biochemistry analyzer after 6 hours in all rabbits. Ventricular fibrillation threshold (VFT) was measured in vivo by bipolar pacing electrodes at 40 days. Cx43 and p-Cx43 distribution in ventricular tissue was detected by immunofluorescence analyses. Cx43 and p-Cx43 protein level in ventricular tissue was determined by Western blot.@*Results@#(1) Plasma LDH ((851.7±85.9)U/L vs. (332.3±39.6)U/L, P<0.01) and CK ((1 192.7±105.3)U/L vs. (462.3±65.6)U/L, P<0.01) were significantly higher in myocardial infarction group than in sham group (both P<0.01). (2) VFT was significantly lower in myocardial infarction group than that in sham group ((470.0±91.0) beats per minute vs. (683.3±60.9) beats per minute, P<0.05), and VFT was significantly higher in early treatment group ((633.3±43.2) beats per minute) and routine treatment group ((645.0±30.8) beats per minute) than in the myocardial infarction group (both P<0.05). (3) Immunofluorescence analyses showed that Cx43 was mainly localized in the intercalated disk, which was perpendicular to the cell long axis with linear arrangement, and less lateral distribution in sham group, early treatment group and routine treatment group, which was significantly different as the case in the myocardial infarction group. The expression of p-Cx43 in myocardial infarction group was less than in sham group, which was significantly upregulated in in early treatment group and routine treatment group when compared with myocardial infarction group, and expression of p-Cx43 was significantly higher in early treatment group than in routine treatment group. (4)The p-Cx43/Cx43 ratio of protein was significantly lower in myocardial infarction group than in sham group (0.165±0.011 vs. 0.363±0.046, P<0.05), and significantly higher in early treatment group (0.720±0.063) and routine treatment group (0.364±0.030) than in myocardial infarction group (both P<0.05), and this ratio was significantly higher in early treatment group than in routine treatment group (P<0.05).@*Conclusion@#Metoprolol treatment, especially the early metoprolol treatment (within 24 hours after LAD ligation), could significantly improve VFT by ameliorating the distribution and dephosphorylation of myocardial Cx43 in rabbits with experimental myocardial infarction.
ABSTRACT
BACKGROUND:Coronary stent implantation can cause blood vessel damage and wal reconstruction, leading to vascular stent restenosis. Studies have found that visfatin is associated with inflammatory reaction, and exhibits an increased expression at the site of plaque rupture in acute myocardial infarction. OBJECTIVE:To investigate the influence of percutaneous coronary intervention on the levels of visfatin in patients with coronary heart disease. METHODS:Thirty patients with acute myocardial infarction within 12 hours after the onset of the chest pain, 30 patients with unstable pectoris and 30 patients with stable angina pectoris were included. Al patients were successfuly treated by percutaneous coronary intervention. Meanwhile, 30 patients only undergoing coronary angiography but not stenting treatment were selected, and another 30 patients without any treatment served as normal control group. RESULTS AND CONCLUSION:According to enzyme-linked immunosorbent method, the visfatin levels of acute myocardial infarction, unstable angina, stable angina and coronary angiography groups continue to rise at pre-operation, 30 minutes, 6 hours, 12 hours, 24 hours after operation, al of which were higher than that in the normal control group (P < 0.05). The results confirmed that within 24 hours after coronary stent implantation the visfatin levels continue to rise.
ABSTRACT
BACKGROUND: Experimental evidence suggests that growth factors can promote myocardial angiogenesis, but the effect and mechanism of basic fibroblast growth factor (bFGF) in controlled release delivered via fibrin glue has not been fully recognized.OBJECTIVE: To evaluate the effect of controlled-release bFGF delivered via fibrin glue in the myocardium on the expressions of vascular growth factors and cell proliferation in the local acute myocardial infarct area in canines, and assess the therapeutic effect of this strategy.DESIGN: Completely randomized controlled experiment.SETTING: Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences; Department of Cardiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology; Shanghai Xinxing Blood Product Research Institute.MATERIALS: This experiment was carried out in the Laboratory of Animal Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, and the Experimental Animal Center of Chinese PLA General Hospital between June 2001 And March 2003.Twelve clean healthy adult mongrel dogs of either sex were selected and randomized into transmyocardial laser revascularization group and bFGF group with 6 in each group.METHODS: With appropriate anesthesia, the chest of the dog was opened and the left anterior descending (LAD) branch of the coronary artery was ligated to establish acute myocardial infarction (AMI) model.The dogs were then randomized into transmyocardial laser revascularization group to receive transmural myocardial penetration 30 minutes after AMI and bFGF group with non-transmural myocardial penetration 30 minutes after AMI and subsequent injection of bFGF-containing fibrin glue into the channel. The expressions of vascular epithelial growth factor (VEGF), transforming growth factor beta 1 (TGFβ1) and proliferating cell nuclear antigen (PCNA) in the loacl ischemic myocardium were examined immunohistochemically (IHC) at postoperative 18 weeks.MAIN OUTCOME MEASURES: Quantitative IHC analysis of VEGF,TGFβ1 and the PCNA expressions in the local ischemic myocardia in transmyocardial laser revascularization group and bFGF group.RESULTS: Five dogs in the transmyocardial laser revascularization group and 6 in the bFGF group survived the operations. Quantitative IHC analysis revealed obviously larger positive area stained for myocardial VEGF,TGFβ1 and PCNA in bFGF group than in transmyocardial laser revascularization group (t=-7.505, -2.690 and -6.895, P ＜ 0.05), and the average absorbance of PCNA staining in bFGF group was greater than that in the transmyocardial laser revascularization group (t= -5.271, P ＜ 0.05).CONCLUSION: Controlled-releasing bFGF delivered in the myocardium can increase local expressions of the vascular growth factors in the ischemic myocardium and enhance cell proliferation, promoting revascularization after AMI.