Aim To research into the effect of diltiazem on cytokines expression in mononuclearcells induced by concanavalin A.Methods Ficoll density gradient centrifugation was used to separate the mononuclearcells from rat's spleen.There were 3 groups including control, Con A, diltiazem-Con A group in the study.The cytokines expressions in supernatant were detected by ELISA.Results Compared with control, IL-10, TNF-α, IL-6 were increased significantly in Con A group with low level IL-1β and non level TGF-β_1.But in diltiazem-Con A group, IL-10, TNF-α, IL-6 were decreased significantly compared with Con A group.Conclusion Diltiazem inhibits IL-10, TNF-α, IL-6 expressions in mononuclearcells induced by Con A.

Aim To explore the cardiac cytokine expression in rat model of myocardial calcium overload, and the intervention from diltiazem.Methods The intracellular Ca~(2+) overload was induced by the isolated rat heart subjected to 5 min Ca~(2+) depletion and 30 min Ca~(2+) repletion (Ca~(2+) paradox) by the Langendorff technique.There were five groups in this study, including Ca~(2+) overload group, normal control group, Ca~(2+) depletion control group, Ca~(2+) overload-diltiazem group, and Ca~(2+) depletion-diltiazem group.The views of myocardial pathology and ultrastruction were observed by electron microscope and light microscope respectively. The cardiac intracellular [Ca~(2+)]_i was detected by atom spectrophotometer. The expression of TNF-α, IL-1β, L-6, TGF-β1, and IL-10 was detected by RT-PCR method.Results In Ca~(2+) overload group, few inflammatory cells were found in myocardium under the light microscope. And the views of electron microscope presented that cardiocyte membranes, nucleolus, and mitochondria were disorganized obviously.Compared with normal control group, the inflammatory cytokines as TNF-α, IL-1β, and IL-6 were increased significantly whereas there was nearly no difference of the expression of TGF-β1 and IL-10 in Ca~(2+) overload group.Ca~(2+) overload-diltiazem group showed that TNF-α, IL-1β, and IL-6 were decreased significantly. There were no statistical differences in the structure of myocardium, intracellular [Ca~(2+)]_i, and cardiac cytokines expressions in the three control groups, including normal control group, Ca~(2+) depletion control group and Ca~(2+) depletion-diltiazem group.Conclusions Instead of TGF-β1 and IL-10, the expression of TNF-α, IL-1β, and IL-6 is increased obviously in myocardium of calcium paradox model. Diltiazem can inhibit the cardiac expression of TNF-α, IL-1β, and IL-6 induced by myocardial calcium overload.

Aim To research the effect of diltiazem on cytokine expression and inflammatory cell activity in rat heart with ischemia/reperfusion.Methods The rats, underwent ischemia reperfusion, were divided into three groups:diltiazem group(D group),ischemia/reperfusion group (I/R group),and sham group (Sgroup).Echocardiogram was detected at 1,2,4 weeks after operation. RT-PCR was used to detect the inflammatory cytokines as IL-1β,TNF-α, IL-6 and anti-inflammatory cytokines as IL-10,TGF-β.Results Compared with I/R group,EF were increased and LVM, IL-β,TNF-α,IL-6 reduced significantly in D group.There was no significant/difference for IL-10 and TGF-β in three groups .Conclusion Diltiazem inhibits IL-1β,TNF-α, IL-6 expressions and inflammatory cell infiltration in rat heart with ischemia reperfusion.

Objective:To explore the effects of diltiazem on ventricular remodeling and inflammation in rat heart following acute myocardial infarction(AMI).Methods:The model of AMI rats was randomly divided into diltiazem group(D group)and control group(AMI group),besides another group of sham operation(S group).The data of ejection fraction(EF) and the left ventricular mass(LVM)were examined with echocardiography,and leukocyte infiltration in situ was analyzed on the HE staining slices,with the expression of proinflammatory cytokines(IL-I?,IL-6,TNF-?)detected by RT-PCR at 1d,3d,1w,2w and 4w intervals after AMI.Results:The results from echocardiography showed that EF increased(73.7?3.1% vs 61.0?2.6%)and LVM decreased(0.81?0.12g vs 0.92?0.12g),both significantly in D group at 4w,compared with those of the AMI group(P

Ca2+ activity has been found to associate with the immunity and inflammation within cardiovascular diseases in recent years. Researchers have begun to focus on the effect of calcium channel blockers, which could modify the immunity and inflammation. This review presented the mechanism underlying the concentration and activation of Ca2+ influenced the response of immunity and inflammation and how calcium channel blockers interfered with it, which may have potential in treatment of cardiovascular diseases.

Objective To study the effect of simvastatin on improve ventricular remodeling in rats after myocardial infarction(MI). Methods The MI models of rat were constructed,and divided into three groups:(1)MI group(MI-C),only ligation of left anterior descending coronary artery(LAD);(2)Simvastatin group(MI-S),ligation of LAD and gavage with simvastatin 40 mg?kg~(-1)?d~(-1);(3)Sham group(sham),no ligation of LAD.Cardiac architecture and function were determined by the echocardiography.The TNF-? mRNA expression in infarction and non-infarction regions was measured by RT-PCR. TNF-? protein was determined by Western blot and immunohistochemical staining.Results The echocardiography showed that the left ventricular end-diastolic diameter(LVEDd,(7.5?0.4)mm versus(4.5?0.3)mm) significantly increased in MI-C group,compared with sham group.The fractional shortening(FS,(20.5?2.5)% versus(51.6?3.1)%) and ejection fraction(EF,(41.4?4.3)%versus(85.2?3.7)%)markedly decreased in MI-C group,while compared with sham group. Simvastatin obviously reduced left ventricle(LV) expansion and improved LV function(P

AIM: Recent studies have identified the importance of inflammation in the development and progression of heart failure.Chemokines are essential factors in the recruitment and activation of leukocytes.They are closely related with inflammation.So the relation between chemokines expression and lymphocytes recruitment and cardiac function after acute myocardial infarction(AMI) was studied.METHODS: Ligating left interventricular branch induced AMI.Experimental rats were divided into three groups: heart failure group(MI-HF),non-heart failure group(MI-NF) and sham group(sham).Sham group was made by the same procedure only without ligation.The blood dynamics of rats was examined after 3 days,1 week and 2 weeks following ligation.Rats,which had a left ventricular end-diastolic pressure(LVEDP) above 15 mmHg,were considered to be in heart failure.Reverse transcription polymerase chain reaction(RT-PCR) was used to analyze the mRNA expression of chemokines,including monokine induced by IFN-?(MIG),macrophage inflammatory protein-1 alpha(MIP-1?) and regulated upon activation,normal T cell expressed and secreted(RANTES),in the infarcted region(circumjacent region included).The numbers of lymphocytes infiltrated in the infarcted region were also counted.RESULTS: MIP-1?,RANTES and MIG mRNA increased at 3 days and reached the peak at 1 week after AMI,significantly higher in MI-HF group than those in MI-NF group(RANTES,0.83?0.05 vs 0.51?0.19,P

Objective:To study the autoimmune response against self myocardial tissue in an experimental rats model of acute myocardial infarction (AMI) and reveal a potential role of autoimmune mediated myocardial injury involved in ventricular remodeling after AMI.Methods:An experimental animal model of AMI was adopted by in vivo ligation of left anterior descending branch (LAD) in Wistar rats After six weeks, spleens were removed and splenocytes were collected About 100?10 6～150?10 6 splenocytes were freshly transferred to syngeneic inbred rats Four weeks later, these recipient rats were anesthetized for hemodynamics analysis by catheter technique Antibody against cardiac myosin heavy chain (MHC) was screened by enzyme linked immunosorbent assay Histopathological studies were performed on all hearts Results:The antibody against cardiac MHC was positive in 8 of 22 AMI rats and recipient rats, and in 0 of 20 sham operation and recipient rats,P

Objective To investigate the relatonahip between TNF-α and ventricular arrhythmias after acute myocardial infarction(AMI)and its mechanism.Method Both the clinical and animal experiments were done.(1)Clinical experiment:Eighty patients with AMI were included in Union Hospital,Tongji Medical College,Huazhong University of Science and Techology,from May 2005 to November 2006 according to the WHO diagnostic criteria.Co-infection of diseases such as severe upper respiratory infection,lung infection,high fever,cancer,et al were excluded.The relationship between the levels of TNF-α and arrhythmias were observed at different times after AMI.A straight line correlation,analysis Was done.(2)Animal experiment:Different concentrations of TNF-αwere added to isohted rat hearts for observing the arrhythrnia effects.The effect of TNF-α on intracellular Ca2+ concentration was detected by laser confocal technique.All data were analyzed by SNK-q test using SPSS 13.0 sofeware prograrn.Results(1)The plasma levels of TNF-α were significantly associated with the Lown class of PVC after AMI and they were higher in AMI of anterior wall[(46.41±10.34)pg/ml]than other positions [(28.25±6.35)pg/ml,P<0.05].2)The frequency of ventricular arrhythmias was interrelated with the concentralions of TNF-α.Using etanercept beforehand,TNF-α induced a slight increase of intracellular Ca2+ intensity (P<0.05).Conclusions There was a relationship between TNF-αlevels and ventricular arrhythmisa in patients with AMI.Animal experiments confirmed the isolated heart perfusion with TNF-α induced ventricular arrhytrnias.Expression of TNF-α after AMI was related with the occurrence of ventricular arrhythrnias.The effect might be associated with the increased inuaeellular Ca2+ intensity caused by TNF-α.

AIM: To explore the molecular mechanisms about fibrosis and transforming growth factor (TGF) - β1 as well as inflammation in rats heart after acute myocardial infarction (AMI). METHODS: AMI model in rats was produced by left coronary artery ligation. Samples of rat cardiac tissue were collected at the end of 1 week, 4 weeks and 8 weeks. Hemodynamics had been performed before rats were sacrificed. Reverse transcription polymerase chain reaction (RT- PCR) and immunohistochemical methods were used to analyze mRNA expression and protein production of TGF- β1, respectively. Hydroxyproline was determined by chloramines T method. HE staining was resorted to analyze pathological myocardium after AMI. RESULTS: There were remarkable differences in hemodynamics between AMI groups and sham group (P＜0.01). Compared with sham group, TGF-β1mRNA expression and protein production and hydroxyproline quantification were enhanced greatly. Among them, the levels of TGF -β1 and hydroxyproline at 1 week were higher than those at 4 weeks or 8 weeks. A positive correlation between TGF- β1 protein and hydroxyproline was presented (r=0.75 - 0.99, P＜0.05). In microscope, leucocytes infiltrated significantly in the infarcted and border myocardium at 1 week after AMI, and were rarely seen at 4 weeks and 8 weeks. TGF - β1 protein were detected in cytoplasm of cardiac myocyte and leucocytes at 1 week, and at 4 and 8 weeks in myofibroblast and interstitial. CONCLUSIONS:TGF- β1 is upregulated and found in cytoplasm of cardiac myocyte and leucocytes as well as myofibroblast in heart after AMI,which is associated with dynamic changes of hydroxyproline content and inflammation. TGF - β1 is showed to play an important role in myocardial inflammatory repair and ventricular remodeling after AMI.