Effects of granulocyte colony-stimulating factor on the myocardial infarction in experimental rats

AIM: To investigate the effects of granulocyte colony-stimulating factor (G-CSF) on the myocardial infarction in experimental rats. METHODS: Rats were randomly divided into GT group and saline control group (SC).The rats of GT group were treated with G-CSF (10 μg/kg) once a day subcutaneously for 5 days and those of SC group were received saline.On the third day, both groups were injected with isoprenaline (ISO) interaperitoneally to develop acute ischemic model. The hearts were harvested from 2 weeks to 4 weeks after administration of ISO for histopathological examination. RESULTS: Compared with saline control group, G-CSF treatment group significantly reduced the scar size (P<0.05). We also found the regeneration of myocytes, smooth muscle and endothelial cells. CONCLUSION: G-CSF treatment could be benefical to the regeneration of infarcted myocardium and significantly reduce scar size and it could be used for therapeutic intervention of the acute myocardial infarction.     

Role of cAMP signaling in cardioprotective mechanism of ischemic postconditioning

AIM: To assess the role of the cAMP signaling in cardioprotection by brief intermittent ischemia at the time of onset of reperfusion (i.e. postconditioning). METHODS: The model of rat myocardial ischemia/reperfusion (I/R) was used. The left ventricular functions were assessed by measuring the left ventricular developed pressure (LVDP) and the coronary flow (CF). The injury of myocardium was further confirmed by detecting the releases of lactate dehydrogenase(LDH) and creatine kinase(CK) in coronary effluent. The mRNA expression of caspase-3, bcl-2 and bax in myocardium was determined by real-time PCR. RESULTS: I/R treatment led to the decrease in LVDP and CF, and the increase in the releases of CK and LDH in coronary artery effluent. The mRNA expression of caspase-3 and bax/bcl-2 ratio was up-regulated simultaneously. Postconditioning treatment relieved the injury induced by I/R, which was enhanced by the specific phosphodiesterase 4(PDE4) inhibitor rolipram. On the other hand, the specific adenylyl cyclase inhibitor SQ22536 attenuated those protective effects of postconditioning. CONCLUSION: The cAMP signaling participates in the protective effect of postconditioning on heart from I/R injury, and the effect may be associated with the regulation of apoptosis.     

Cardioprotection of ischemic postconditioning against ischemia/reperfusion injury in isolated rat hearts

AIM: To investigate the protective role of postconditioning in myocardial ischemia/reperfusion in rats and its mechanisms. METHODS: Cardiac contractility was analyzed by the Langendorff method. Infarct size was determined by dual staining with triphenyltetrazolium chloride and Even's blue dye, and the cardiac arrhythmia was evaluated. postconditioning was conducted by 3 cycles of 30 s ischemia followed by 30 s of reperfusion at the beginning of subsequent persistent reperfusion. RESULTS: Left ventricular systolic pressure (LVSP) and maximal rise rate of ventricular pressure (+dp/dt_max) were higher during reperfusion in postconditioning group compared with control. postconditioning reduced the infarct size in ischemia/reperfusion rat hearts. The cardiac arrhythmia score was decreased in postconditioning group in the first 10 min of reperfusion followed by ischemia compared to control group. postconditioning had similar cardioprotective effect as preconditioning. 5-HD, a selective mitochondrial ATP-sensitive potassium channel (mitoK_ATP) inhibitor, blocked the amelioration of contract function provided by postconditioning. It also abolished the protective effect of postconditioning on cardiac arrhythmia score and infarct size. CONCLUSION: The results show that postconditioning has cardioprotective effect and attenuates reperfusion injury in ischemic heart. The effect might be partly through the activation of mitoK_ATP channel.     

Effect of ischemic post-conditioning on myocardial mitochondrial function in isolated rat heart

AIM: To investigate the protective effect of ischemic post-conditioning on isolated rat myocardial mitochondrial function during ischemia/reperfusion, and to study the role of mitochondrial ATP-sensitive potassium channel (mitoK_ATP) in myocardial protection. METHODS: Sprague-Dawley male rats were randomized into 4 groups (n=8 in each group): control group (C), model group (M), ischemic post-conditioning group (IPO) and 5-hydroxydecanoate plus IPO group (5-HD+IPO). The hearts isolated from the SD rats were mounted on a Langendorff apparatus and started with a 20-minute perfusion for equilibration. In C group, the hearts went on perfusion for another 70 min after equilibration. In M group, 4 ℃ St. Thomas cardioplegic solution was administered prior to ischemia, followed by ischemia for 40-minute, and reperfusion for another 30 min. In IPO group, the hearts underwent 40-minute global ischemia after equilibration, then perfusion for 10 s and ischemia for another 10 s. The procedure was repeated 6 times before 28-minute reperfusion. In 5-HD+IPO group, the hearts were perfused with 5-HD (100 μmol/L in K-H solution) and treated as that in IPO group, then reperfusion for 23 min. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and respiratory function of myocardial mitochondria were measured at the ends of equilibration and reperfusion. RESULTS: (1) Compared with the data collected at the end of equilibrium, the MMP was obviously decreased at the end of reperfusion in all groups, The highest in C group. MMP in 5-HD+IPO group was markedly higher than that in IPO group and M group. MMP in IPO group was higher than that in M group. (2) In contrast to that at the end of equilibrium, ROS was obviously increased at the end of reperfusion in all groups. However, ROS was observably higher in M group than that in the other 3 groups, and ROS in 5-HD+IPO group was markedly higher than that in IPO group and C group. ROS in IPO group was higher than that in C group. (3) The respiratory function of mitochondria was obviously injured at the end of reperfusion in all groups. The arrangement of the mitochondrial respiratory function from the best to the worse was C group > IPO group > 5-HD+IPO group > M group. CONCLUSION: Ischemic post-conditioning attenuates myocardial reperfusion injury by maintaining the stability of MMP, decreasing the generation of ROS and preserving the respiratory chain function of mitochondria. The mitoK_ATP antagonist 5-HD can not completely block the myocardial protective effect of ischemic post-conditioning. Myocardial protective effect of ischemic post-conditioning may achieve by activating mitoK_ATP, meanwhile the other factors may also take part in the myocardial protective processes.     

Preliminary investigation on combining autologous marrow stromal cells transplantation with granulocyte colony stimulating factor for improvement of rabbit cardiac performance after actue myocardiac infarction

AIM: To test the hypothesis that autologous marrow stromal cells (MSCs) transplantation combined with granulocyte colony stimulating factor (G-CSF) can enhance cardiac function of ischemic hearts in vivo.METHODS: In order to achieve a safe and persistent effect,we explored the potential of autologous MSCs transplantation.Acute myocardial infarction induced by occlusion of left anterior descending artery,autologous MSCs labeled with BrdU bromodeoxyuridine in vitro were administered intramyocardially into the infarct area of the same donor rabbits and G-CSF was administrated by subcutaneous injection.Four weeks later,the transplanted labeled MSCs were detected by laser scanning confocal microscopy and the cardiac functions were examined by echocardiogram and multichannel physiologic recorder.Myocardial infarct size was measured from mid-transverse sections stained with Massons trichrome.RESULTS: After 4 weeks,transplanted MSCs were demonstrated myogenic differentiation with the expression of α-sarcomeric actin and connexin 43 located in intercalated disk.MSCs combined with G-CSF transplantation improved the left ventricular contractility and reduced myocardial infarct size markedly compared to that without G-CSF tratment.CONCLUSION: Our finding indicates that autologous MSCs combined with G-CSF transplantation may represent a promising therapeutic strategy on ischemic heart disease.     

Inhibitory effect of ischemic postconditioning on autophagy induced by focal cerebral ischemia reperfusion in rats

AIM: To investigate the effect of ischemic postconditioning (IPC) on autophagy induced by focal cerebral ischemia reperfusion (I/R) in rats. METHODS: Healthy male SD rats were assigned randomly into sham-operation (sham) group, I/R group and IPC group with 10 rats in each group. The rats in sham group were only exposed the right common, internal and external carotid artery surgically. The rats in I/R group were subjected to right middle cerebral artery occlusion (MCAO) by the modified Longa suture method for 2 h followed by 24 h of reperfusion. The rats in IPC group were subjected to MCAO for 2 h followed by reperfusion of the ipsilateral common carotid artery occlusion for 10 s for 5 episodes, and then reperfusion for 24 h. Autophagy was obeserved by transmission electron microscopy (TEM). The protein levels of mammalian target of rapamycin (mTOR), p-mTOR and microtubule associated protein light chain 3 (LC3)-II in brain tissue of the rats were determined by Western blot. Pathological changes of brain tissue were observed by HE staining. RESULTS: The protein levels of mTOR and p-mTOR in IPC group were significantly higher than those in I/R group (P<0.05). The expression of LC3-II in IPC group was significantly lower than that in I/R group (P<0.01). The cerebral infarction area and brain water content in IPC group were significantly lower than those in I/R group (P<0.01). HE staining showed that neurons degeneration and necrosis in IPC group were significantly alleviated compared with I/R group. TEM observation showed that IPC revealed fewer autophagosomes, with much less severe cell damage than that in I/R group. CONCLUSION: IPC reduces brain ischemia reperfusion damage by decreasing autophagy of brain cells, which might be related to the activation of mTOR.     

Protective effect of rapid ischemic preconditioning against spinal cord ischemic injury in rabbits

AIM: To evaluate the protective effect of rapid phase of ischemic preconditioning against spinal cord ischemic injury in rabbits. METHODS: Thirty six male New Zealands white rabbits were randomly assigned to 3 groups (12 in each group): ischemia and reperfusion injury group (IR group), ischemic preconditioning + IR group (IPC+IR group) and sham operation group (sham). In IR group, spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min; The rabbits in IPC+IR group underwent a 6 min ischemic preconditioning followed by 30 min of reperfusion before the 20 min clamping; The rabbits in sham group underwent the same procedures as the IR group except for infrarental aortic unclamping. Neurologic status was scored at 8, 12, 24 and 48 h after reperfusion. All animals were sacrificed at 48 h after reperfusion and the spinal cords (L_5-7) were removed for histopathologic study and determination of the activity of Na⁺, K⁺-ATPase. RESULTS: The neurologic function scores in sham group and IPC+IR group at each observation interval were higher than those in IR group (P＜0.01). Compared to IR group, there were more normal neurons in anterior horn of spinal cord in sham group and IPC+IR group (P＜0.01); the activity of Na⁺, K⁺-ATPase in sham group and IPC+IR group were higher than those in IR group (P＜0.01). CONCLUSION: The rapid phase of ischemic preconditioning has a protective effect against spinal cord ischemic injury in rabbits, and this neuroprotection may be related to the maintenance of Na⁺, K⁺-ATPase activity.     

Protective effect of ischemic preconditioning on rat brain with ischemia/reperfusion injury

AIM:To study whether ischemic preconditioning(IPC) has a protective effect against ischemia/reperfusion(I/R) injury in brain, and the possible relationship between IPC and the regulating function of microcirculation.METHODS:The I/R models were established both in I/R and IPC groups of Sprague-Dawley rats. Additional procedure was performed of short term cerebral ischemic preconditioning in IPC group 24 hours before I/R. Skull windows were performed through which microcirculation features were measured before ischemia, during ischemia, and reperfusion. Finally, brains were cut into slices and stained with red tetrazoline(TTC).RESULTS:Most TTC stained brains in I/R group presented irregular palely red areas which were few in IPC group. Compared with I/R group, IPC group presented relatively increase in accumulated length of capillaries, mean cerebral microcirculatory perfusion, and microcirculatory velocity in ischemic and reperfusion phase. There was no-reflow phenomenon in I/R group in reperfusion phase, which was substituted by the course of increasing reperfusion in IPC group.CONCLUSIONS:IPC could relieve the reduction of tissue perfusion during ischemia and the no-reflow phenomenon during reperfusion by improving the regulating function of microcirculation, which relatively promote the opening of capillaries and accelerating of microvascular flow, therefore protect brain from I/R injury.     

Effect of Fas/FasL on late reperfusion of acute myocardial infarction and the potential oxidative stress mechanism in canine

AIM: To discuss the effect of Fas/FasL on the late reperfusion of acute myocardial infarction (AMI) and the potential oxidative stress mechanism. METHODS:Eighteen anesthetized dogs were randomly divided into three groups: late reperfusion group (n=6): ligated the coronary for 6 h, followed by reperfusion for 6 h; permanent ischemia group (n=6): after pericardium were opened for 6 h, ligated the coronary for 6 h, and did not reperfuse; control group (n=6): did not ligate the coronary but operation last for 12 h. Infarction brim myocardial Fas/FasL was detected by immunohistochemistry. Apoptosis index (AI) was detected by TUNEL. SOD and GR activity and MDA content were detected by colorimetry. RESULTS:The expression of Fas/FasL and apoptosis index were significantly higher in permanent ischemia group and late reperfusion group than those in control group (P<0.05, P<0.01), and the difference between them was also significant (P<0.05). SOD and GR activities were lower in permanent ischemia group and late reperfusion group than those in control group (P<0.05, P<0.01). The MDA contents in permanent ischemia group and late reperfusion group were higher than that in control group (P<0.05). CONCLUSION:The late reperfusion of AMI promotes the expression of Fas/FasL and myocardial apoptosis, and it may be due to oxidative stress mechanism.     

Short-term cardioprotective effects of trimetazidine on acute myocardial infarction in rats

AIM: To observe the myocardial protective effects of trimetazidine on myocardial infarction (MI) in Sprague-Dawley (SD) rats. METHODS: Ninety SD rats were randomly assigned to 3 groups (n=30 each): myocardial infarction group (MI group), MI+trimetazidine group (MT group) and sham group (S group). By permanently ligating the left anterior descending artery, the MI model was set up in the rats in MI group and MT group. Before and after setting up the MI model, normal saline was given to the rats in MI and S group by gavage. On the other hand, trimetazidine (3 mg/kg,twice per day) was given to the rats in MT group by gavage. At 8 h, 24 h and 48 h after applying trimetazidine, the serum level of cardiac troponin I (cTnI) was measured. At the 1st week, 2nd week and 4th week after treated with trimetazidine, the size of myocardial infarction, the maximum rising rate of the left ventricular systolic pressure (+dp/dt_max) and the maximum descending rate of the left ventricular diastolic pressure (-dp/dt_max) were measured. Also at the 1st week after applying trimetazidine, the cardiomyocyte apoptotic index was detected. RESULTS: Compared with MI group 2 weeks after applying trimetazidine, +dp/dt_max significantly increased in MT group , and -dp/dt_max also significantly increased in MT group . Four weeks after applying trimetazidine, +dp/dt_max significantly increased in MT group , and -dp/dt_max also significantly increased in MT group . At 8 h and 48 h after applying trimetazidine, no statistically significant difference (P＞0.05) of serum cTnI between MI group and MT group was observed. However, at 24 h after applying trimetazidine, the serum level of cTnI decreased in MT group as compared with MI group . Aditionally, trimetazidine significantly decreased the infarction size of myocardium in MT group (0.248±0.052) as compared with MI group (0.362±0.082, P<0.01). CONCLUSION: Trimetazidine has short-term cardioprotective effects on the rats with acute MI by improving myocardial systolic and diastolic functions, reducing infarct size and inhibiting apoptosis.     

Mechanisms underlying the protective effect of renal ischemic preconditioning on ischemia-reperfusion myocardium of rabbits

AIM: To investigate the mechanisms underlying the protective effect of kidney ischemic preconditioning on rabbit myocardium in case of ischemia-reperfusion and the possible role of oxygen free radicals in the process. METHODS: Animals were divided into four groups: ischemia/reperfusion(I/R), classical ischemic preconditioning(CIPC), kidney ischemic preconditioning (KIPC) and superoxide dismutase in combination with kidney ischemic preconditioning(SOD+KIPC). The endo genous myocardial pretective material, nitric oxide(NO) and 5'-nucleotidase(5'-NT) were checked in four groups. RESULTS: As compared with I/R group, both CIPC and KIPC could ameliorate left ventricular function, reduce plasma PLA₂ activity and arrhythogenic rate also, the myocardial 5'-NT and NO production were significantly higher than that of the rabbit of I/R group. However, the protective effect on rabbit myocardium was significantly weakened by the SOD administration before the ischemic preconditioning. CONCLUSION: Protective effect of KIPC on myocardium may be due to increase in endo genous myocardial protective materials, oxygen free radicals may play an important role in the endo genous myocardial protective material release.     

MicroRNA profile analysis of ischemic myocardial tissues from rats with acute myocardial infarction

AIM：To identify differentially expressed microRNAs (miRNAs) in ischemic myocardial tissues from the rats with acute myocardial infarction (AMI) by miRNA array technique, and to predict their targets and analyze their functions using bioinformatics. METHODS：The rat models of AMI (n=3) were prepared by ligaturing the left anterior descending coronary artery (LAD) of Wistar rats. Electrocardiogram and blood pressure were detected during the operation, and the myocardial infarct size was measured by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Ischemic myocardial tissues were isolated from the infarct area 4 h after ischemia. The same procedure in sham group (n=3) was performed except for ligaturing LAD. Total RNA was extracted from ischemic and normal myocardial tissues. miRNA was isolated from total RNA, labeled with Cy3 and hybridized on miRNA array. Real-time PCR was applied to verify the reliability of miRNA array results. The targets of differentially expressed miRNAs were predicted and their functions were analyzed by bioinformatics. RESULTS：Rat model of AMI was successfully prepared and verified by electrocardiogram detection, blood pressure measurement and pathological observation. Compared with sham group, microarray screening showed that total 11 AMI-related miRNAs were selected, including 6 up-regulated and 5 down-regulated. Three of them (rno-miR-181c, rno-miR-146b and rno-miR-208) were related to the cardiovascular functions, while the functions of the others (rno-miR-672*, rno-miR-743b, rno-miR-128, rno-miR-138-1*, rno-miR-336, rno-miR-138-2*, rno-miR-325-3p and rno-miR-3572) were unknown and might be novel AMI-related biomarkers. Parts of the miRNA targets were also related to the cardiovascular functions. CONCLUSION：Differentially expressed miRNAs in AMI rats may serve as novel biomarkers for diagnosis of AMI and potential targets for treatment of AMI.     

Combinational effects of trimetazidin and parecoxib on acute myocardial infarction in rats

AIM: To investigate the protective effects and mechanisms of combinational use of trimetazidine(TMZ) and parecoxib sodium on acute myocardial infarction (AMI) in rats. METHODS: Sixty-six Sprague-Dawley rats were randomly divided into 5 groups: sham group; AMI group; AMI+TMZ group; AMI+parecoxib group; AMI+TMZ+parecoxib group. All rats were sacrificed and cardiac functions (HR, LVSP, LVEDP, +dp/dt_max,-dp/dt_max) were measured with a Pclab-3804 biological signal processing system on the 8th day. The infarct size in each group was checked up by TTC staining method. RT-PCR was employed to detect the bax mRNA and bcl-2 mRNA. The protein levels of COX-2, Bax, Bcl-2 and cleaved caspase-3 in myocardium were determined by Western blotting. The activity of caspase-3 in each group was measured by colorimetric assay kit, and the apoptotic rates were detected with DNA ladder kit.RESULTS: Compared with sham group, increased expression of COX-2 protein (P<0.01) was observed in AMI group. The expression of COX-2 protein in parecoxib group was lower than that in AMI group (P<0.01). Compared with AMI group, the combinational use of trimetazidin and parecoxib improved contractile functions (LVSP and +dp/dt_max), reduced the infarct size and lowered the apoptotic rates remarkably. Specifically, the combinational use of trimetazidin and parecoxib showed better effects than use of trimetazidin or parecoxib alone. Reduced expression of Bax/Bcl-2 mRNA and protein, the reduced caspase-3 activity and cleaved caspase-3 expression were also found in combinational group as compared with other groups (P<0.05).CONCLUSION: The combinational use of trimetazidin and parecoxib effectively improves cardiac functions and reduces infarct size. The mechanism of the protective effect is probably associated with inhibiting apoptosis of cardiac myocytes.     

Endogenous basic fibroblst growth factor is a protective factor against myocardial ischemia/reperfusion injury of rats

AIM: To observe the role of exogenous and endogenous basic fibroblst growth factor (bFGF) on myocardial ischemia/reperfusion(I/R) injury of rats.METHODS:bFGF and bFGF antiserum were applied to rat isolated I/R heart. Myocardial function, coronary effluent volume,protein and myoglobin content as well as LDH activity in coronary effluent fluid, myocardial calcium, MDA and ATP concentration as well as PKC, MAPK activity were measured. RESULTS:Compared with control, myocardial function in I/R group significantly decreased. Protein, myoglobin content and LDH activity in coronary effluent liquid as well as myocardial MDA and calcium content increased, while myocardial ATP concentration decreased(all P＜0.01). Compared with I/R group, ±LV dp/dt_max in bFGF group increased by 43% and 26%, respectively. LVEDP decreased by 40%. HRr/HRi and B/A augmented by 42% and 20%, respectively. Protein and myoglobin content as well as LDH activity lowered by 29%,30％ (all P＜0.01) and 33％ (P＜0.05) respectively. Myocardial MDA and calcium content decreased by 44% and 35%, respectively, while myocardial ATP level as well as PKC and MAPK activity increased by 34%,41％ and 10% (all P＜0.01), respectively. In bFGF antiserum group, ±LV dp/dt_max were 35% and 38% lower than those in I/R group. LVEDP increased by 93%. HRr/HRi and B/A decreased by 36% and 45%, respectively. Protein and myoglobin content as well as LDH activity augmented by 54%,96％ (all P＜0.01) and 34％ (P＜0.05) respectively. Myocardial MDA and calcium content increased by 24% and 50%, respectively, while myocardial ATP level as well as PKC and MAPK activity lowered by 28%,21％ and 8% (all P＜0.01), respectively. CONCLUSION:Endogenous bFGF is a protective factor against myocardial ischemia/reperfusion injury of rats.     

Changes of serum vascular endothelial growth factor levels in a rat model of acute myocardial infarction

AIM and METHODS: To study the changes of serum vascular endothelial growth factor (VEGF) levels in a rat model of acute myocardial infarction (MI) and its significance. Eighty-eight male Sprague-Dawley rats were used in this study. MI was produced by left coronary arterial ligation in 80 animals, and eight rats undergoing thoracotomy but not coronary ligation served as controls (sham).Blood samples were drawn from the right atrium before (sham animals) and 1, 3, 6, 12, 24 hours and 2, 3, 5, 7, 14 days after MI(n=8, respectively). Serum VEGF concentrations were measured by a sensitive enzyme-linked immunosorbent assay with a rabbit polyclonal antibody specific for VEGF. RESULTS: In 8 sham animals, the concentration of serum VEGF was (66.99±17.83) pg/mL. Six hours after MI, the level of serum VEGF significantly increased to (125.68±28.07)pg/mL (P＜0.01 vs sham control), and reached a peak (240.61±70.63 pg/mL, P＜0.01 vs sham control) at 24 hours after ligation and then decreased gradually over the remaining 2 weeks. But the level remained significantly elevated for 14 days (107.64±30.31 pg/mL, P＜0.01 vs sham control).CONCLUSION: Serum VEGF levels markedly and permanently increase in the rat model of acute MI may play an important role in the angiogenesis associated with MI     

Cardiomyocyte apoptosis and expression of Bcl-2, Bax protein after acute myocardial infarction and late reperfusion in dogs

AIM: To study the effect of late reperfusion on apoptotic cardiomyocytes in the risk area of acute myocardial infarctin in dogs. METHODS: The experiment was divided into three groups: sham operation group, acute myocardial infarction (AMI) group, and late reperfusion (LR) group. Apart from sham operation group, the other two groups were subjected to left anterior descending branch of coronary artery ligation. The acute myocardial infarction group was only subjected to ligation for 12 hours, late reperfusion group was subjected to ligation for 6 hours following by 6 hours of reperfusion. The cardiomyocyte apoptosis was measured by TUNEL assay. Immunohistochemistry and Western blotting analysis were used to detect the expression of Bcl-2 and Bax protein. RESULTS: The number of apoptotic cardiomyocytes in late reperfusion group was much less than acute myocardial infarction group (P<0.05), and increased significantily as compared with sham operation group (P<0.01). The expression of Bcl-2 protein was enhanced gently in late reperfusion group in contrast to acute myocardial infarction group, but no significant difference in the two groups (P>0.05) was observed, although it was much more in the two groups than that in sham operation group (P<0.01). The expression of Bax protein in late reperfusion group was much higher than that in sham operation group (P<0.01), and was lower than that in acute myocardial infarction group (P<0.05). CONCLUSION: Late reperfusion reduces cardiomyocyte apoptosis in the risk area of acute myocardial infarction. The mechanism may be that late reperfusion can decrease the expression of Bax protein.     

Study on the potential to differentiate into myocytes of the CD34+ cells

AIM:To investigate the potential of differentiatng into myocytes of the granulocyte colony-stimulating factor(G-CSF)-mobilized CD34⁺ cells. METHODS:Three hours after intraperitoneal injecction of isoprenaline(ISO)to develop acute ischemic model,rats’bone marrow hematopoietic stem cells were mobilized to the site of myocardial infarction by G-CSF.The techniques of immunohistochemisty and HE stain were used to detect the infiltration of CD34⁺ cells and the regeneration of myocytes in the infarct zones. RESULTS:24 hours after administration of ISO, a large amount of infiltrative monocytes and regenerative myocytes which were CD34 positive expression could be found in the infarct zones of the G-CSF treatment group, while majority of the infiltrative inflammatory cells in control group were neutrophils and there was no infiltrative cells and myocytes which were CD34 positive expressio, 2 weeks after administration of ISO, there were a plenty of scar in control group, but not in the G-CSF treatment group. CONCLUSION:G-CSF-mobilized CD34⁺ cells possess the potential to differentiate into myocytes and it may be used in treating acute myocardial infarction.     

Role of dendritic cells in myocardial infarction and cardiac remodeling

Myocardial infarction （MI） is one of the leading causes of death worldwide. One of the primary reasons is that the rupture of atherosclerotic plaque leads to the formation of thrombosis, and then interrupts the coronary blood flow, thus finally causing the death of myocardial cells and cardiac dysfunction. A large number of researches have revealed that dendritic cells （DCs） play an essential role in immune inflammatory responses in the occurrence and development of atherosclerosis and MI. This article reviews the role of DCs in atherosclerosis, myocardial ischemia/reperfusion injury and cardiac remodeling after MI, and shows the potential values of DCs as an immunotherapeutic strategy for MI.     

Effect of amiodarone and metoprolol on platelet activation,fibrinolytic activity and vasoactive mediators in acute myocardial infarction in rabbits

AIM:To explore the significance of platelet activation, fibrinolytic activity and the changes of vasoactive mediators in acute myocardial infarction in rabbits and the intervention of amiodarone and metoprolol.METHODS:Fifty New Zealand white rabbits were randomly assigned to five groups, ten for each. Group Ⅰ: sham group, group Ⅱ: acute myocardial infarction(AMI) group, group Ⅲ: AMI and lidocaine group, group Ⅳ: AMI and amiodarone group, group Ⅴ: AMI and metoprolol group.The middle point of left ventricular coronary artery was ligated (groupⅡ,Ⅲ, Ⅳ and Ⅴ ) or a sham ligation(group Ⅰ). Four hours later, blood was collected for measuring plasma concentration of TXB₂, 6-Keto-PGF_1α, ET, NO, plasma activity of t-Pa and PAI.After that, the heart was taken out to evaluate the infarction size(IS).RESULTS:Plasma concentration of TXB₂, ET, NO and plasma activity of PAI were significantly higher in groupⅡ,Ⅲ, Ⅳ and Ⅴ than those in group Ⅰ(P＜0.01), but the plasma concentration of 6-Keto-PGF_1α and plasma activity of t-Pa were remarkably lower in groupⅡ,Ⅲ, Ⅳ and Ⅴ than those in group Ⅰ(P＜0.01). There were no difference in plasma concentration of TXB₂, 6-Keto-PGF_1α, t-Pa activity and infarction size in group Ⅱ,Ⅲ and Ⅳ(P＞0.05).Compared to group Ⅱ, plasma concentration of ET, NO and PAI activity were significantly decresed (P＜0.01)in group Ⅳ. Plasma concentration of TXB₂, ET, NO and plasma activity of PAI were significantly lower in groupⅤ than those in group Ⅱ(P＜0.01). Conversely, plasma concentration of 6-Keto-PGF1 and plasma activity of t-Pa were remarkably higher in group Ⅴ than those in group Ⅱ(P＜0.01). The infarction size was remarkly decrease(P＜0.01)in group Ⅴ.CONCLUSIONS:Amiodarone inhibited PAI avtivity, decreased release of ET and NO in AMI in rabbits. Metoprolol inhibited platelet activation, improved fibrinolytic, decreased release of ET and NO, and reduced myocardial infarction size in AMI in rabbits; Lidocaine had no effect above.