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

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

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.

Objective To evaluate the effects of selected decontamination of the digestive tract(SDD) on intestinal derived endotoxmia,inflammation mediator and clinical outcome in patients of rheumatic heart disease undergoing valve replacement operation with cardiopulmonary bypass(CPB).Methods Thirty patients with CPB were randomly divided into control group(n=15) and treatment group(SDD group,n=15).The patients in control group routinely took preoperative preparation while those in treatment group orally administrated Tobramycin 100 mg,garlicin 40 mg and Lactulose 10ml three times per day in addition to routinely preoperative bowel preparation.The levels of endotoxin,D-lactate,TNF-? and complement 3 were measured at four time points of anesthetic induction,CPB end,2 h and 24 h after CPB.Results The level of D-lactate in the patients of SDD group was significantly lower than that of the control group at time points of anesthetic induction and 2 h after CPB(P0.05).Conclusion The endotoxemia can be induced by CPB.The regime of SDD is an effective way of preventing endotoxemia,but it may not have effect on inflammation medium and clinical outcome.

Objective To investigate the role of cell apoptosis in the gut mucosal barrier dysfunction in rats undergoing cardiopulmonary bypass(CPB) . Methods The rat model of CPB was set up. The rats were divided into CPB group, sham operation(SO) group and normal control group. The morphological changes of ileum mucosal tissues were observed by microscope and electron microscope at 3h, 6h, 12h and 24h after operation, respectively. The apoptotic index of gut mucosal epithelial cells was measured with TUNEL method. Results Gut mucosal morphology was normal in CPB group at 3h, 6h and 12h after operation, but gut mucosal epithelial desquamation occurred at 24h after operation. Typical apoptotic cells could be seen with electron microscope in CPB group at every time point. Apoptotic index of gut mucosal epithelial cells significantly increased in CPB group at every time point compared with SO group, and peaked at 6h after operation. Apoptotic cells were mostly located in the gut crypt. Conclusion The data suggested that the apoptosis of intestinal epithelial cells significantly increased at early stage of post-CPB in rats, which might contribute to gut mucosal barrier dysfunction.

Objective To investigate the effect of chronic atrial fibrillation on free calcium concentration and expression of Ca 2+ /calmodulin dependent protein kinase Ⅱ (CaMKⅡ) in human atrial myocytes. Methods The intracellular free calcium concentration in rapidly isolated atrial myocytes and the expression of CaMKⅡ in atrial tissue of rheumatic heart disease patients with atrial fibrillation (AF) or with normal sinus rhythm were measured by laser scanning confocal microscopy and Western blotting respectively. Results The intracellular Ca 2+ concentration of patients with atrial fibrillation was significantly higher than that of patients with normal sinus rhythm [(276.38?38.12) vs (122.28?45.63) nmol/L, (P

Objective To design and construct the vector of protein-rich tyrosine kinase 2 small RNA interference and investigate the effect of the recombinant plasmid on the proliferation of adult rat cardiac fibroblasts. Methods The pAVU6+27-PYK_2 siRNA expression vector was constructed by gene recombination, then transfected into the cultured adult rat cardiac fibroblasts by DOTAP method. PYK_2 mRNA and protein in cardiac fibroblasts were determined by RT-PCR and Western blotting respectively. Cell proliferation was tested by MTT and ~3H-TdR incorporation. Results The pAVU6+27-PYK_2 siRNA expression vector was successfully constructed. The recombinant plasmid can inhibit the proliferation of adult rat cardiac fibroblasts, as compared with control. Conclusion pAVU6+27-PYK_2 siRNA expression vector is efficient to suppress DNA synthesis of cardiac fibroblasts, which will be beneficial to further study of myocardial fibrosis.

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.