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.

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 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

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 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

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

AIM: The study was designed to explore the autoimmune mechanism of myocardial injury and ventricular remodeling after acute myocardial infarction (AMI). METHODS: An experimental animal model of AMI was adopted in Wistar rats. After 6 weeks, splenocytes were freshly transferred to syngeneic inbred rats. Four weeks later, these recipient rats were anesthetized for hemodynamics analysis by catheter technique. Serum antibody against cardiac myosin heavy chanin (MHC) was screened by ELISA. Histopathological studies were performed on all hearts. The phenotypes of T lymphocytes in myocardium were analyzed by histocytochemistry stain. RESULTS: Histopathological studies showed the lymphocytes infiltration in non-infarction myocardium in AMI rats and the organ specific inflammation of myocardium in all succedent recipient (AMI-T) rats. Histocytochemistry stain revealed the predominant CD4+T cells infiltration in myocardium. The antibody against MHC was examined in 8/22 cases of AMI rats and AMI-T rats, but none in sham-T rats. The left ventricular dysfunction was found in AMI-T rats, which was characterized by slight decline of ~+dp/dt_~max. CONCLUSIONS: The study showed inflammatory response of non-infarction myocardium in AMI rats and demonstrated the lymphocytes-mediated myocardial injury and cardiac dysfunction by adoptive transfer of splenocytes of AMI rats. The autoimmune-mediated myocardial injury might be a novel mechanism of ventricular remodeling after AMI. [

AIM: The study explored the significance of the imbalance of Th1/Th2 function after acute myocardial infarction (AMI). METHODS: Peripheral blood mononuclear cells from 33 AMI patients, 22 unstable angina (UA) patients and splenocytes from 35 AMI rats were collected. Cytokine-producing Th cells were monitored by 3-color flow cytometry after stimulated with phorbol myristate acetate (PMA) and ionomycin. IFN-? and IL-4 mRNA in the rat myocardium and chemokine receptors CCR3, CCR5 and CXCR3 mRNA on the surface of rat T lymphocytes after AMI were measured by RT-PCR. RESULTS: Th1 associated cytokine IFN-? significantly increased in patients with AMI and UA within 24 hours after the onset of symptom. the high ratio of IFN-?-producing T cells lasted short in patients with UA and recovered 1 week after the onset. In AMI patients, the high ratio of IFN-?-producing T cells could be examined 1 week and even 1 month after the onset. There was no significant difference on the frequencies of IL-4-producing peripheral T cells between each group. 1 week, 2 weeks and 1 month after AMI, IFN-? mRNA increased in the myocardium of rats, but there was no significant change on cytokine-producing Th cells and chemokine receptors on the surface of rat T lymphocytes. CONCLUSIONS: The Th1/Th2 functional imbalance and up-regulation of Th1 cell-functions exist after AMI and perhaps participate in the onset of AMI. Th1/Th2 functional imbalance may participate in the immune-mediated myocardial injury and ventricular remodeling after AMI as one of the pathogenesises of autoimmune disease.