Effect of β3-adrenoceptors on Ventricle Fibrillation Threshold and Effective Refractory Period in Rats With Heart Failure

Objectives To observe the effect of β3-Adrenoceptor （AR） on ventricle fibrillation threshold （VFT） and effective refractory period （ERP） in rats with heart failure. Methods Rats were randomized into control group and heart failure group. The expression of β3-ARmRNA was detected with RTPCR; The VFT, ERP, LVESP,LVEDP, ＋dp/dtmax and -dp/dtmax was measured at the same time with administration of BRL37344 （ 2 nmol / kg, β3- AR agonist）. Results ①Both the expression of β3-AR mRNA and the proportion increased in rats with heart failure in comparison with control rats （0.028 vs. 0.011 and 5.4% vs 1.2%, P 〈 0.05）;② ERP was longer in rats with heart failure than control group （70.5±5.5 ms vs 59.5±6.4ms, P 〈 0.05） and there was no difference of ERP in rats with heart failure with administration of BRL37344 （73.0±4.8 ms vs 70.5± 5.5 ms, P 〉0.05）; ③VFT was lower in rats with heart failure than control group（10.9±0.8 mv vs 30.5± 1.3 mv, P〈 0.05） and decreased obviously in rats with heart failure with administration of BRL37344 （7.1±0.6 mv vs 10.9±0.8 mv, P 〈 0.05） ; The decrease of VFT correlated with the effect on LVESP, ＋dp/ dtmax,-dp/dtmax of BRL37344 and the expression of β3-AR mRNA （correlation coefficient： 0.788, 0.708, 0.759, 0.787; P 〈 0.05）. Conclusions The expression of β3-AR mRNA of left ventricle was obviously increased in rats with heart failure, and activation of β3-AR had no effect on ERP but could decreased VFT which correlated with the effect of β3-AR on LVESP, ＋dp/dtmax, -dp/dtmax and the expression of β3-AR mRNA.     

Effect of β blockers on β_3-adrenoceptor mRNA Expression in the Rats with Chronic Heart Failure

Objectives To investigate the changes of β3-adrenoceptor (β3-AR) mRNA expression in the rats with chronic heart failure (CHF), and to explore the effect of β blockers (βBs) on β3 mRNA expression. Methods Thirty-four rats were randomly divided into Sham group (n = 10) and heart failure group (n = 24). Rat model was established by aortic constriction. The survival rats in heart failure group were divided into heart failure control group (HF group, n = 6), metoprolol group (MET group, n = 8) and carvedilol group (CAR group, n = 8) three months after operation. Metoprolol tartarte was started orally with 12 mg·kg-1·d-1, carvedilol with 6 mg·kg-1·d-1, isometric saline was started in HF group. After three months of drug therapy, measurement of hemodynamics, index of ventricular mass, the level of β3-AR mRNA expression were performed. Results Compared with Sham group, left ventricular end systolic pressure (LVESP), and the absolute values of maximal rate of rise and fall ( ± dp/dtmax) of left ventricular pressure were all significantly decreased (P < 0.01), left ventricular end diastolic pressure (LVEDP) was significantly increased in HF group (P < 0.01). The hemodynamic parameters were improved by βBs, and carvedilol was more effective than metoprolol (P < 0.01). The index of ventricular mass was higher in HF group than MET group, CAR group and Sham group (P < 0.01). βBs significantly decreased the index of left ventricular mass (LVMI), and Carvedilol was more effective than metoprolol (P < 0.01). The index of right ventricular mass (RVMI) did not change in MET group (P > 0.05), but significant decrease could be seen in CAR group (P < 0.01). The level of β3-AR expression in left ventricle was greater than that in right ventricle whether in the failing heart or in the non-failing heart. Compared with Sham group, the level of β3-AR mRNA expression was significantly increased in HF group (P < 0.01). The levels of β3-AR mRNA expression showed a remarkable decrease in CAR group(P < 0.01), but was not seen in MET group. Conclusions The β3-AR expression level remarkably increases in the rat's left and right failing ventricles. Carvedilol is more effective on improving hemodynamics and attenuating ventricular remodeling than metoprolol in the rats with CHF. Carvedilol rather than metoprolol downregulates β3-AR expression in the rat's failing ventricles. The beneficial effect of carvedilol in CHF maybe partly due to the downregulation of β3-AR expression in the failing heart.     

The Regulation Effects of β2-AR on INCX in Myocytes from Infarcted Rat Heart

Objectives This study is designed to investigate the regulation effects of β2-adrenergic receptors （AR） on expression of the Na^± - Ca^2 ± exchanger （ INCX） in myocytes from the infarcted rat heart. Methods Twenty-eight adult Wistar rats were randomly divided into four groups ： the control group, the two weeks, four weeks and eight weeks post-myocardial infarction （post-MI） groups, respectively. The chest of rat was opened and a ligature was placed around the left anterior descending coronary artery. Rats in control group were sham-operated without the coronary artery ligation. After the operation, rats were fed for two, four or eight weeks respectively. Myocytes were enzymatically disassociated by Langendorff perfusion. The whole cell-patch clamp recording technique was used to record INCX in specific pipette solution and superfusion according to the specific holding potential and command potential program. Results The INCX in ventricular myocytes from the border zone of infarcted myocardium increased significantly at eight weeks after MI （0. 51 ± 0. 12 pA/pF vs 1.07± 0. 21 pA/pF, P 〈0.05）. β2-AR agonist increased INcx more strongly in myocytes from post- MI heart than in controls. β2-AR antagonist attenuated the rise of INCX, strongly in myocytes from post-MI heart than in controls, whereas β1-AR onist. Conclusion The regulation effects of β2-AR on INCX in myocytes AR had closer relationship with the genesis of malignant arrhythmia afte     

Effects of Long-term Ramipril on Ventricular Remodeling, Cardiac Function and Survival in Rat Congestive Heart Failure after Myocardial Infarction

Objectives The purpose ofthis study was to investigate the effects of long-termramipril on ventricular remodeling, cardiac functionand survival in rat congestive heart failure after my-ocardial infarction. Methods Myocardial infarction(MI) was caused by ligation of the left anterior de-scending coronary artery in rats. 7 days after thesurgery, the surviving rats were randomly assigned tothe following treatment protocols: 1) MI ras with notherapy, 2) MI rats treated with ramipril 3 mg/kg perday, 3) Sham-operated control rats, and 4) Sham-op-erated rats treated with ramipril 3 mg/kg per day. At22 weeks, cardiac hemodynamic parameters such asMAP, LVSP, ±dP/dtmax and LVEDP were measured,and cardiac morphometric parameters such as HW,LVW and LVCA were measured, mRNA of cardiacmolecule genes, such as βMHC, BNP, collagen Ⅰ andⅢ, and TGF-β_1, were quantified, and survival rateswere calculated. Results Compared with sham-operated rats, MI rats without therapy showed significantincreases in cardiac morpholog     

Dynamic changes of α-AR,β1-AR and β2-AR expression during hepatic fibrogenesis

Objective To investigate the dynamic changes of α-AR,β1-AR and β2-AR expression in hepatic fibrosis.Methotis Rat hepatic fibrosis model was established by bile duct ligation(BDL).HE and Masson staining were used to determine hepatic fibrosis levels.Immunohistochemistry was applied to detect α-sooth muscle actin(α-SMA),a marker of hepatic stellate cell(HSC)activation;Western blot and realtime RT-PCR were used to measure the dynamic changes of α-AR,β1-AR,β2-AR expression on protein and mRNA levels.respectively,during the development of hepatic fibrosis.Results(1)HE and Masson trichrome staining showed that the liver fibrosis modeIs were established successfully.(2)At 1,2,3,4 wk after BDL,α-SMA positive area density of the model group(10.58%±1.75%,24.1 4%±2.02%,29.74%±2.59%,34.28%±2.01%)was significantly higher than that of the sham operation group (4.12%±1.51%),P＜0.01.(3)The expression of α-AR,β1-AR,β2-AR protein and mRNA was increased with the development of the hepatic fibrosis(P＜0.05).(4)α-SMA expression Was positively associated with α-AR,β1-AR,β2-AR,r values were 0.564,0.753 and 0.606,respectively.Conclusions The expression of α-SMA is increased dramatically during the fibrosis,and is positively associated with the expression of α-AR,β1-AR and β2-AR.     

Clinical Analyses of Senile Retrogressive Cardiovalvulopathy-Report of 126 Cases

Objectives To investigate the clinical characteristics and the diagnostic methods of senile retrogressive cardiovalvulopathy（SRC）. Methods Total 126 cases had heart murmurs or complicated with congestive heart failure were selected into study. The diagnosis of SRC was detected by Echocardiography （UCG）, chest X-ray, electrocardiography （ECG）and clinical data. The characteristics of clinical data included symptoms, signs, heart function and the prognosis, the features of UCG included quantify and positions of valvulae in pathosis, index of heart function, and the special findings of chest X-ray and ECG were analysed. Results The murmurs were found in total 126 cases complicated with different heart sounds and in different intensity in auscultate, 119 patients were complicated with acute or chronic heart failure in different levels of heart function from Ⅱ -Ⅳ（NYHA）. All the patients were received UCG examination, 126 cases had different calcifications with different extent and single or mixed valves were involved. The left ventricle heart function of systole and diastole were impaired. The mean LVEF was （35 ± 0.7）%, In chest X-ray test： The ratio between heart and chest in larger than 50% were found in 122 cases. The ECG examination in total 84 patients shown that atrial premature beats were in 65 patients, atrial fibrillation or atrial flutter in 75 patients, ventricle premature beats 41 patients. Conclusions The results suggest that elder patients with heart murmurs, congestive heart failure or cardiac arrhythmias should be advised to received a UCG examination, SRC should be considerd, and other heart disease should be distinguished by UCG.     

Effects of AT1 Antagonist on MMP2, MMP9 Expression and Collagen Remodeling in Left Ventricle of Rabbit Undergoing Chronic Pressure Overload

Objectives To study the effects of AT1 antagonist on MMP2, MMP9 expression and collagen remodeling in left ventricle of rabbit undergoing chronic pressure overload. Methods 30 rabbits were randomly divided into 3 groups (n= 10,each group), including sham operation group, abdominal aorta banded group(banded group), abdominal aorta banded valsartan group (valsartan group).Twelve weeks after operation,hemodynamic parame-ters were acquired, then collagen volume fraction(CVF) and MMP2, MMP9 expression of left ventricle were measured by using VG and immunohistochemical stain. Results Compared with sham operation group, both MMP2 and MMP9 expression were enhanced in banded group; meanwhile, LVW/BW,LVEDP and CVF increased significantly. Compared with banded group, both MMP2 and MMP9 expression were weakened in valarstan group; simultaneously,LVW/BW, LVEDP and CVF decreased significantly.Conclusions Expression of MMP2 and MMP9 was enhanced in left ventricle of rabbit undergoing chronic pressure overload, which may be associated with collagen proliferation, ventricule remodeling and impaired heart function; Valsartan could inhibit collagen proliferation, prevent ventricule remodeling and preserve heart function by inhibiting abnormal expression of MMP2 and MMP9.     

Doppler Tissue Imaging Assessment of Left Ventricular Systolic Dyssynchrony in Severe Heart Failure Patients With a Normal QRS Duration

Objectives To assess the prevalence of systolic dyssynchrony of the left ventricular （LV） walls in patients of heart failure（HF） with a normal QRS duration by Doppler tissue imaging （DTI）. Methods 20 patients of HF with a normal QRS duration and 20 healthy individuals were investigated with DTI to quantitatively analyze their pulsed-wave Doppler spectrum of basal and middle segments in six walls of left ventricle. The time between the onset of the QRS complex of the surface ECG and the onset of the systolic wave of pulsed-wave Doppler spectrum was measured （TS）. LV systolic synchronization was assessed by the maximal difference （MD） in time of TS, the standard deviation （SD） and the coefficient of variation （CV） of TS in the all 12 LV segments. Results When a TS-MD of TS〉 53.08 ms, a TS-SD of TS 〉18.08 ms and a TS-CV of TS 〉 0.91 （＋1.65 SD of normal controls） was used to define significant systolic dyssynchrony, the prevalence of systolic dyssynchrony was 55.0 %, 55.0 % and 55.0 %, respectively, in the HF patients group, significantly higher than those in the normal control and the locations of delayed contraction of these patients were different. Conclusions LV systolic dyssynchrony could be commonly demonstrated by DTI in HF patients with a normal QRS duration. This finding will support the view about the possibility that more HF patients could benefit from cardiac resynchronization therapy.     

Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.     

Clinical efficacy and predictor of cardiac resynchronization therapy on left bundle branch block-associated heart dysfunction

Background Left bundle branch block （LBBB） results in an altered pattern of left ventricular （LV） activation and subsequent contraction. Cardiac synchrony and cardiac function are deteriorated by LBBB. However, the effect of LBBB history on progressive heart dysfunction and clinical efficacy of cardiac resynchronization therapy （CRT） in such patients are not clear. In this study we explore the clinical efficacy and predictor of cardiac resynchronization therapy in LBBB heart dysfunction. Methods Twenty-seven LBBB patients with severe heart failure were treated with CRT. Twenty-six LBBB patients without CRT served as control. During 6 months follow-up, ECG, plasma NT-proBNP and echocardiogram indexes were measured. Results Compared with baseline, NYHA functional class of 23 patients （85.2%） was improved in CRT group. Compared with baseline and control, QRS duration （QRSd） was significantly more narrow （P = 0.023, P = 0.019）, NT-proBNP was significantly lower （P = 0.011,P = 0.009）, ventricular septal to left ventricular posterior wall delay time and left ventricular dyssynchrony index （Ts-SD） were significantly worse （P 〈 0.05）; left ventricular ejection fraction, left ventricular end-systolic volume, mitral regurgitation area were significantly improved in CRT group （P 〈 0.05）. when the LBBB history was I〉 2 years and QRSd I〉 155 ms, the sensitivity and specificity of CRT super-response were 53.4% and 85.6% respectively. Conclusions CRT can improve the synchronization and hemodynamic of LBBB patients with heart dysfunction, the LBBB history I〉 2 years and QRSd I〉 155 ms are one of the CRT super-response predictors.     

The role of endotoxin,TNF—α,and IL—6 in inducing the state of growth hormone insensitivity

AIM：Critical illnesses such as sepsis,trauma,and burns cause a growth hormone insensitivity,wehich leads to an increased negative nitrogen balance.Endotoxin is generously released into blood under these conditions and stimulates the production of proinflammatory cytokines such as TNF-α,IL-6,and IL-1 which may play a very important role in inducing the growth hormone insensitivity,The objective of this current study was to investigate the role of endotoxin,TNFα and IL-6 in inducing the growth hormone insensityvity at the receptor and post-receptor levels.METHODS:Spageu-Dawley rats were injected with endotoxin,TNF-α,and IL-6,respectively and part of rats injected with endotoxin was treated with exogenous somatotropin simultaneously,All rats were killed at different time points,The expression of IGF-I,GHR,SOCS-3 and β-actin mRNA in the liver was detected by RT-PCR and the GH levels were measured by radioimmunoassay,the levels of TNF-α and IL-6 were detected by ELISA.RESULTS:There was no significant difference in serous GH levels between experimental group and control rats after endotoxin injection,However,liver IGF-1 mRNA expression had been obviously down-regulated in endotoxeminc rats.Liver GHR mRNA expression also had a predominant downregulation after endotoxin injection,The lowest regulation of liver IGF-I mRNA expression occurred at 12h after LPS injection,being decreased by 53% compared with control rats.For GHR mRNA expression,the lowest expression occurred at 8h and had a 81% decrease.Although SOCS-3 mRNA was weakly expressed in control rats,it was strongly up-regulated after LPS injection and had a 7.84 times increase compared with control rats.Exogenous GH could enhance IGF-1 mRNA expression in control rats,but if did fail to prevent the decline in IGF-1 mRNA expression in endotoxemic rats,Endotoxin stimulated the production of TNF-α and IL-6,and the elevated IL-6 levels was shown a positive correlation with increased SOCS-3 mRNA expression.The liver GHR mRNA expression was obviously down-regulated after TNF-α iv injection and had a 40 decresase at 8 h,but the liver socs-3 mRNA expression was the 4.94 times up-regulation occurred at 40 min after IL-6 injection.CONCLUSION:The growth homone insenstivity could be induced by LPS injection,which was associated with down regulated GHR mRNA expression at receptor level and with up-regulated SOCS-3 mRNA expression at post-receptor level The in vivo biological activities of LPS were mediated by TNF-α and IL-6 indirectly,and TNF-αand IL-6 may exert their effects on.the receptor and post-receptor levels respectively.     

Effect of captopril on myocardial energy metabolism in chronic pressure overload rats

Objective To investigate the effects of captopril on cardiac function and levels of energy-rich phosphates in pressure overload induced left ventricular hypertrophy rats. Methods One hundred and twenty SD rats were randomly divided into three groups： sham operation group （SH group, n=40）,coarctation of abdominal aorta group （CAA group, n=40） and captopril treatment lmg~ 100g1 ~ d-1） group （CAP group, n=40）. Left ventricular end-diastolic pressure （LVEDP）, left venh-icular mass index （LVMI）, levels of energy-rich phosphates and morphological changes of the myocardial mitochondria were compared at the 62 and 82 week after operation. Results At 62 week, in CAA group, LVMI and LVEDP were increased and _ dp/dtmax was decreased, while ATP and ADP were decreased and AMP was increased （P〈0.01）. These changes were much obvious at 8th week （P〈0.01）. Compared with those of CAA group, the parameters of heart function and energy-rich phosphates （ATP, ADP, AMP, TAN） in CAP group were improved significantly（P〈0.01） at the 6th and 8th week. In CAP group, the parameters of heart function and energy-rich phosphates （ADP, AMP, TAN） were much better at 8~ week than those at 6th week. The morphological change of mitochondria was less in CAP group than that in CAA group. Conclusion Captopril significantly improves myocardial energy metabolism in pressure overload rats and protects the function of myocardial mitochondria     

Effect of SecinH3 on lung injury induced by sepsis of rats

Objective:To study effect of SecinH3 on lung injury induced by the sepsis of rats.Methods:A total of 30 SPF Wistar rats were randomly divided into two groups,including 5 rats in the control group and 25 in the model group.The intraperitoneal injection of endotoxinlipopolysaccharide(LPS) was performed to build the animal model of sepsis.The blood gas analysis was carried out.Afterwards,change in the expression of pro-inflammatory factors of IL-1,IL-6 and TNF- a in the serum were detected.To study the mechanism of SecinH3 in the process of lung injury induced by the sepsis,the rats with the successful modeling of sepsis were randomly divided into two groups.Rats in the SecinH3 group were given the intraperitoneal injection of 100 μg/12 h SecinH3 for 24 h;while rats in the control group were given the injection of same solvent by the same dosage.The blood was drawn from the heart by 500 μL for the blood gas analysis to detect the change in the expression of proinflammatory factors of IL-1,IL-6 and TNF-α in the treatment group and control group.After separating the lung tissue,the Real-time PCR and western blotting were performed to analyze the effect of SecinH3 on the expression of cytohesins and also discuss the change of epidermal growth factor receptor(EGFR) and p-EGFR related to the signaling pathway of EGFR-p38mitogen-activated protein kinase that is regulated by cytohesins.Results:Three rats died within 4 h after the injection of LPS,while other 22 ones had the successful modeling,with the success rate of 88%.After being stimulated by LPS,compared with the control group,the arterial partial pressure of oxygen of rats in the treatment group was significantly reduced(P0.05),while the partial pressure of CO_2 was significantly increased(P0.01).After being treated by SecinH3,Pa/O_2 was increased with the sepsis,while Pa/CO_2 was decreased with the action of SecinH3,which indicated that SecinH3 had the certain 'repairing' ability for the lung injury.SecinH3 might inhibit the cytohesins and then inhibit the phosphorylation of EGFR.Conclusions:SecinH3 can significantly inhibit the cytohesins and then relieve the lung injury induced by the sepsis of rats.     

β_1-adrenergic receptor(Arg389Gly) polymorphism and response to bisoprolol in patients with chronic heart failure

Objective The purpose of this study was to investigate the relation between the Arg389Gly polymorphism of theβ1-AR gene and chronic heart failure (CHF) and to evaluate the effect of this polymorphism on clinical response toβ-adrenoceptor blockade (bisoprolol) in patients with CHF. Methods One hundred and ten patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 3 months af-     

Expression of β-catenin in hepatocellular carcinoma

AIM: The β-catenin has been recognized as a critical member of the Wnt signaling pathway and plays an important role in the generation/differentiation of many tissues. Inappropriate activation of this pathway has been implicated in carcinogenesis. The mechanism underlying the development as well as its prognosis of hepatocellular carcinoma (HCC) has remained unclear. The purpose of this study is to analyze the expression of β-catenin in HCC in relation to histological grades and viral hepatitis backgrounds. METHODS: Thirty-two sections were selected at random from autopsy and surgical cases of HCC. Immuohistologically, the location and positivity of β-catenin expression in HCC was examined. RESULTS: Normal hepatocytes did not express β-catenin. In 78% of HCC β-catenin was expressed at the membrane of the cells, with or without cytoplasmic and/or nuclear expression. The tumor cells with well- and moderately-differentiated grades expressed frequently at the membrane and cytoplasm compared with poorly-differentiated type. Nuclear expression of β-catenin was prone to occur in the tumor cells of poorly-differentiated grade. There were 15% of hepatitis C virus (HCV) backgrounds with nuclear expression. In contrast, there was 38% with nuclear expression in hepatitis B virus (HBV) backgrounds. In nonBnonC hepatitis, no case expressed nuclear β-catenin. CONCLUSION: The β-catenin expression in HCC cells was heterogenous among types of hepatitis viral infection. Wnt signaling pathway might be deeply involved in less-differentiated HCC and HBV background.     

Establishment of a chronic left ventricular aneurysm model in rabbit

Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm （LVA） in rabbits. Methods Acute myocardial infarction （AMI） was induced in 35 rabbits via concomitant ligation of the left anterior descending （LAD） coronary artery and the circumflex （Cx） branch at the middle portion. Development of AMI was co n-firmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar i n-tra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure （LVESP） and diastolic pressure （LVEDP） were measured before, immediately after and four weeks after ligation. D i-mensions of the ventricular chamber, thickness of the interventricular septum （IVS） and the left ventricular posterior wall （LVPW） left ventricular end diastolic volume （LVEDV） and systolic volume （LVESV）, and ejection fraction （EF） were recorded by echo-cardiography. Results Thirty one （88.6%） rabbits survived myocardial infarction and 26 of them developed aneurysm （83.9%）. The mean area of aneurysm was 33.4% ＆#177; 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the left ventricle （LV） that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. Conclusions Ligation of LAD and Cx at the middle portion could induce develo pment of LVA at a mean area ratio of 33.4%＆#177;2.4%which involves the apex, anterior wall and lateral wall of the LV.     

Valsartan prevents the development of rabbit’s heart failure by restoring calcium uptake ofsarcoplasmic reticulum

Objective Clinical evidence has suggested that AT1 receptor blocker （ARB） could prevent the development of heart failure. Decreased sarcoplasmic reticulum（SR） Ca2＋ content, which is due to reduced SR calcium reuptake by SERCA2a, is responsible for defective systolic function in failing heart. To better understand how ARB could improve cardiac systolic dysfunction, we studied the effects of Valsartan on calcium reuptake of SR and its regulatory proteins in heart failure rabbits. Methods Thirty rabbits were divided into three groups： sham rabbits（controls, n=11）, rabbits with heart failure treated with Valsartan （n=11） and rabbits with heart failure but without Valsartan treatment （n=8）.Rabbit heart failure model was established by volume plus pressure overload. Cardiac function was measured by echocardiography, SR calcium uptake was determined by measuring extra vesicular free [Ca2＋] changes in a fluorescence spectrophotometer. SERCA2a, Ser 16-phosphorylated phospholamban （p-PLB）, PKA and PP 1 a protein abundance were determined by use of Western blot analysis. Results Compared to control rabbits, the ejection fractions in the HF rabbits were significantly decreased （P〈0.05）, these changes could be significantly attenuated by Valsartan treatment （P〈0.05）.Calcium reuptake of SR, activity of SERCA2a and PKA decreased in heart failing myocytes （P〈0.05）, with down regulations of p-PLB, SERCA2a and PKA, but up regulation ofPP la in ventricular samples from the failing rabbits （P〈0.05）. All of these changes were attenuated by Valsartan treatment （all P〈0.05）. Conclusion Valsartan improved cardiac function in volume plus pressure overload induced heart failure of rabbits possibly by restoring the SR calcium uptake resulted from attenuating the activities and expressions of SERCA2a and its regulatory proteins （J Geriatr Cardio12009; 6：173-177）.     

Effect of Chaiqinchengqi decoction on sarco/endoplasmic reticulum Ca~（2＋）-ATPase mRNA expression of pancreatic tissues in acute pancreatitis rats

AIM： To investigate the effect of Chaiqinchengqi decoction （CQCQD） on sarco/endoplasmic reticulum Ca2＋-ATPase （SERCA） mRNA expression of pancreatic tissues in acute pancreatitis （AP） rats. METHODS： Thirty Sprague-Dawley （SD） rats were randomized into control group, AP group and CQCQD group （n = 3 × 10）. The rats in the CQCQD group were intragastrically administered with CQCQD （10 mL/kg every 2 h） after induction of AP by intraperitoneal injection of caerulein （50 μg/kg.h × 5） within 4 h. At 6 h after the induction of AP model, pancreatic tissues were collected for the pathological observation, mRNA extraction for determination of SERCA1 and SERCA2 mRNA expression or pancreatic acinar cell isolation for measurement of fluorescence intensity （FI） of intracellular calcium ion concentration [Ca2＋ i. RESULTS： There was no expression of pancreatic SERCA1 mRNA in the control group and the AP group. The expression of pancreatic SERCA2 mRNA in the AP group was down-regulated （expression ratio = 0.536; P = 0.001） compared with the control group, while that in the CQCQD group was up-regulated （expression ratio= 2.00; P = 0.012） compared with AP group. The FI of intracellular [Ca2＋ of pancreatic acinar cells in the AP group （138.2 ± 23.1） was higher than the C group （111.0 ± 18.4） and the CQCQD group （118.7 ± 15.2 ） （P 〈 0.05） and the pancreatic pathological score in the CQCQD group was lower than that in the AP group （5.7 ± 1.9 vs 9.2 ± 2.7, P 〈 0.05）.CONCLUSION： CQCQD can up-regulate the expression of SERCA2 mRNA of pancreatic tissues, reduce intracellular calcium overload and relieve pancreatic tissue lesions.     

Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity

Background Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity. Methods Sprague–Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively) for six weeks. Transthoracic echocardiography was performed to evaluate the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. Results Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. Conclusions Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.