BACKGROUND: Peroxisome proliferator-activated receptor-gamma(PPAR-γ) can restrain the inflammatory reaction of hypertrophic myocardium through restraining the expression of interleukin-6, cyclooxygenase, endothelin-1, nitricoxide synthase, matrix metalIoproteinase-9, gelatinase and adhesion molecule, etc.OBJECTIVE: To observe the influence of rosiglitazone sodium(the ligand for PPAR-γ) on inflammatory factors in rats with myocardial hypertrophy in the course of myocardial hypertrophy resulting from pressure load.DESIGN: Randomized controlled trial based on animals.SETTING: Department of Cardiovascular Surgery, Xinqiao Affiliated Hospital, the Third Military Medical University of Chinese PLA.MATERIALS: Fifty purebred male SD rats of S.P.F. Grade, whose body mass was (220±22) g.METHODS: The experiment was completed in the Institute of Battle Surgical Research, the Third Military Medical University of Chinese PLA from August 2004 to October 2005. Fifty rats were randomly divided into 5groups: control group, sham operation-normal saline group, sham operationrosiglitazone group, myocardial hypertrophy-normal saline group and myocardial hypertrophy-rosiglitazone group, 10 rats per group. The rat model of myocardial hypertrophy induced by pressure overload was established with the method of coarctation of abdominal aorta. Rosiglitazone group: At the postoperative 4th week, the rats were injected intraperitoneally with the Normal saline group: At the postoperative 4th week, the rats were injected intraperitoneally with normal saline[1 mL/(kg.d)] for 1 week. At the postoperative 5th week, the indexes of myocardial hypertrophy and hemodynamics were determined. The contents of tumor necrosis factor-α, platelet activating factor and myeloperoxidase in the left ventricle muscle were determined with radioimmunosorbent technique. The expression of PPAR-γ mRNA was detected with RT-polymerase chain reaction. The activity of nuclear factor-κB was detected with EMSA.MAIN OUTCOME MEASURES: The indexes of hemodynamics, cardiac ventricle reconstitution and cardiac muscle in the rat models.RESULTS: Except 1 rat in the control group died of the external injury induced by biting after 3 weeks, 49 of 50 rats entered the result analysis.①After the coarctation of aorta, the contents of tumor necrosis factor-α, platelet activating factor and myeloperoxidase of hypertrophic myocardium in the myocardial hypertrophy-rosiglitazone group were lower significantly than those in the myocardial hypertrophy-normal saline group(P ＜ 0.01-0.05), but they were still higher than those in the control group(P＜0.01).②The expressions of PPAR-γ mRNA of myocardial tissue in both the myocardial hypertrophy-rosiglitazone and myocardial hypertrophy-normal saline groups were higher obviously than those in the control group(P＜0.01), and those in the myocardial hypertrophy-rosiglitazone group were higher than those in the myocardial hypertrophy-normal saline group(P＜0.01).③The activity of nuclear factor-κB combined with DNA in cardiac muscle cell in both the myocardial hypertrophy-normal saline and myocardial hypertrophy-rosiglitazone groups were higher obviously than those in the control group (P＜0.01), and those in the myocardial hypertrophy-rosiglitazone group were lower obviously than those in the myocardial hypertrophy-normal saline group(P＜0.01).CONCLUSION: The increasing of pressure load induces myocardial hy pertrophy. The activation of nuclear factor-κB in the tissue of hypertrophic myocardium is strengthened obviously. The expressions of tumor necrosis factor-α, platelet activating factor and myeloperoxidase in hypertrophic myocardium increase. This inflammatory reaction, which is strengthened obviously, can be restrained by rosiglitazone sodium that is the synthetical lig and for PPAR-γ.

0.05).Platelet aggregation was decreased on the 2nd postoperative day and significantly increased on the 4th postoperative day (P

Objective To investigate the effects of rosiglitazone, an synthetic ligand of peroxisome proliferator activated receptor-?(PPAR-?) on the expression of proinflammatory factors in rats of myocardial hypertrophy. Methods The rat model of hypertrophy were established by coarctation of abdominal aorta in male SD rats, and the rats with myocardial hypertrophy were treated with rosiglitazone or physiological saline (n=10 for each therapy). Some rats underwent sham operation and were given rosiglitazone or physiological saline (n=10 for each therapy). Rosiglitazone at the dose of 4 mg?kg -1?d -1 or saline of 1 ml?kg -1?d -1 was given intraperitoneally for 1 week after postoperative 4 weeks. Another 9 rats served as control. Hemodynamics, ventricular hypertrophic index, TNF-?, PAF, MPD, PPAR-? and NF-?B were detected in all rats at postoperative 5 week. Results Significant hypertrophy was found in the left ventricle in rats undergoing the coarctation of abdominal aorta. The myocardium level of TNF-?, PAF, MPD was higher in rats with myocardial hypertrophy than in rats undergoing sham operation at postoperative 5 weeks (P

Objective To study the effects and mechanisms of growth hormone(GH) pretreatment on the inflammatory response of liver in rats after cardiopulmonary bypass(CPB).Methods The CPB model in rat was established.The rats were randomly divided into GH pretreatment group(GH group),CPB group,and sham group.The serum levels of endotoxin,TNF-?,and liver function were determined at different intervals respectively.Simultaneously,the liver tissues were collected for the detection of the CD14 mRNA and TNF-? mRNA by RT-PCR.Results Compared with pre-CPB,the serum levels of endotoxin,TNF-? were significantly increased,and the lesion of liver function was apparent in GH group and CPB group.Meanwhile,the expression of CD14 mRNA and TNF-? mRNA in liver tissues were also increased obviously in both groups.However,the serum levels of endotoxin and TNF-? and the expression of CD14 mRNA and TNF-? mRNA in liver tissues at the same time point in GH group were significantly lower than those in CPB group(P

Objective To observe the localization and expression of hepatocyte growth factor(HGF),c-Met and Caspase-3 in pulmonary arterioles during the formation process of pulmonary arterial hypertension(PAH) induced by left to right shunt in rats,and explore the effect of HGF and c-Met in the formative process of PAH.Methods Eighty male SD rats(aged 4-5 weeks) were randomly divided into control group and shunt group(40 each).Rats in shunt group underwent right common carotid artery-external jugular vein shunt with cannulation to reproduce PAH model of left to right shunt,and animals in control group only received sham operation.Pulmonary hemodynamic and pathologic examination were performed 4,8,12 and 16 weeks after operation in both groups,while the expression of HGF,c-Met and Caspase-3 proteins in pulmonary arterioles were determined by immunohistochemisty at the above time points.Results Pulmonary artery systolic pressure(PASP),mean pulmonary arterial pressure(mPAP) and the ratio of pulmonary to systemic circulation flow(Qp/Qs) were obviously increased in rats with A-V shunt compared with controls at all time points after operation(P

Objective In the heart,autophagy is important for the turnover of organelles at low basal levels under normal conditions,but is upregulated in response to stresses such as ischemia/reperfusion and in cardiovascular diseases such as heart failure. It can prevent the heart from injury under stress conditions. This study was designed to test the hypothesis that autophagy would be upregulated in the myocardium of children with cyanotic congenital cardiac defects. Methods Eighteen children with cyanotic (n=10) or acyanotic cardiac defects (n=8) who were admitted in our hospital from October 2008 to April 2009 and received surgical treatment were investigated. Samples from the right ventricular myocardium taken immediately after aortic clamping were morphologically studied with transmission electron microscopy for the ultrastructure. Microtubule-associated protein 1 light chain 3 (LC-3) was detected by Western blot analysis in the obtained samples. Results Children with cyanotic cardiac defects had higher oxyhemoglobin saturation before operation than those with acyanotic cardiac defects. Electron microscopy showed that the former group had more mitochondria,disordered arrangement,swollen endoplasmic reticulum and typical autophagosomes in the myocardial cytosol. LC3-II were significantly elevated in patients with cyanotic compared with those with acyanotic congenital cardiac defects (P

Objective To investigate the roles of the expressions of B cell lymphoma-2 (bcl-2) and Bcl-assosiated X (bax) in the pulmonary vascular remodeling (PVR) of pulmonary arterial hypertension (PAH) secondary to left-right shunt congenital heart disease (CHD).Methods A total of 80 SPF SD rats were randomly divided into 8 groups,shunt groups (SⅠ,SⅡ,SⅢ and SⅣ) and control groups (CⅠ,CⅡ,CⅢ and CⅣ).PAH rat model was established in the shunt groups by left-to-right shutting,and the control groups received sham operation.The rats from Ⅰ,Ⅱ,Ⅲ and Ⅳ groups were sacrificed in 4,8,12 and 16 weeks after operation.Mean pulmonary arterial pressure (mPAP) was recorded.Pathologic observations were made to assess pulmonary vascular remodeling.Their lung tissues were detected by in situ hybridization histochemistry (ISHH) technique and Western blotting for bcl-2 and bax.And apoptosis of pulmonary artery smooth muscle cells (PSMCs) and endothelial cells (ECs) were also detected by TUNEL.Results After 12 weeks or 16 weeks shunt,following indexes of the shunt groups were significantly higher than the control groups (P

Objective To study the potential effect of verapamil for the early changes of L-type calcium channel ?1c and potassium channel Kv4.3 in a rapid paced primary cultured atrial myocyte model for atrial fibrillation. Methods Primary rat atrial myocytes were cultured and established a rapid paced primary cultured atrial myocyte model. Atrial cells were divided into four groups: control group, rapid pacing group, verapamil with rapid pacing group and verapamil without rapid pacing group. Durations of rapid pacing were 24 h. The mRNA and protein expressions of L-type calcium channel ?1c and potassium channel Kv4.3 were measured by RT-PCR and Western blotting respectively. Results It was found that 24 h pacing significantly reduced mRNA and protein expressions of L-type calcium channel ?1c and potassium channel Kv4.3 as compared to controls (P0.05). Conclusion Expressions of L-type calcium channel ?1c and potassium channel Kv4.3 were reduced in the rapid pacing atrial myocytes, suggesting ion channel remodeling of atrial myocytes. However, verapamil can attenuate the progression of ion channel remodeling of atrial myocytes at least in early phase.

Obiective To investigate the influence of rapid atrial pacing(RAP)on the expression of ?1c subunit of L-type calcium channel,and the protective effect of verapamil.Methods 30 rabbits were randomly assigned into RAP group and verapamil pre-conditioned group.Each group was further divided into 5 subgroups(n=3 for each subgroup).Electrode was embedded in the right atrium through right external jugular vein.Pacing was performed for 6h,12h,24h and 48h in different subgroups.No pacing in the sham operation group.For verapamil pre-conditioned group,the drug was intravenously administered(0.2mg/kg)30 minutes before the initiation of rapid atrial pacing.Right atrium tissue was harvested for determination of mRNA and protein expression of L-type calcium channel subunits by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.Results The mRNA level of ?1c subunit started to be reduced 6h after rapid atrial pacing(RAP)and continued to decline as pacing continued,and the expression of protein was parallel with mRNA.Otherwise,the mRNA level of ?1c subunit started to decrease 24h after RAP and continued to decline while pacing continued,and the expression of protein paralleled with that of mRNA in verapamil pre-conditioned group.Verapamil can attenuate the down-regulation of L-type calcium channel of the atrium induced by RAP only at 24h after RAP,but the effect was less intent.Conclusion mRNA and protein expression level of L-type calcium channel subunits decreased after RAP,The calcium channel blocker verapamil can attenuate the down-regulation of L-type calcium channel of atrium induced by RAP resulting in a decrease or postponement of calcium overload in atrial myocytes,thus exerting protective effects on atrial electrical remodeling,but such effects vanished after prolonged pacing.

Objective To investigate the change of intestine mucosal permeability during cardiopulmonary bypass (CPB) and its effect on gut barrier in rats model. Methods The rats model of CPB was established and samples of tissue and plasma were collected at different intervals. Plasma D-lactate and LPS concentrations were determined and gut tissue was examined microscopically. Results The plasma concentration of D-lactate and LPS increased gradually at 1h CPB, and increased markedly 1h after CPB. They recovered to normal 8h after CPB, respectively. In addition, it was noted that there was a significant positive correlation between the plasma concentrations of LPS and D-lactate (r = 0.8312, P