Effects of Polysaccharides Extracted from Zhu Zi Shen(Rhizoma Panacis Majoris) on Oxidative Stress and Hemodynamics in Rats with Adriamycin-induced Chronic Heart Failure

Objective:To probe into the intervening action of polysaccharides of Zhu Zi Shen(Rhizoma Panacis Majoris)(PZZS) on oxidative stress and hemodynamics in rats with adriamycin-induced chronic congestive heart failure(CHF).Methods:After SD rats were successfully modeled with adriamycin,they were randomly divided into a normal control group,a model group,a PZZS group,and a captopril group,and were administrated respectively.At the end of experiment,the hemodynamic function,whole heart weight index,and the blood CK,SOD,MDA,NO,NOS were detected;and the myocardial morphological examinations were carried out.Results:Compared with the normal control group,the arterial systolic pressure(SBP),diastolic pressure(DBP),mean arterial pressure(MAP),heart rate(HR),left ventricular systolic peak(LVSP),and left ventricular pressure change rate(dp/dtmax) significantly decreased,and left ventricular end diastolic pressure(LVEDP),whole heart weight index,the blood CK,MDA,NO,NOS significantly increased in the model group.PZZS significantly improved the hemodynamic function,lowered the MDA and NO levels,and decreased the CK and NOS activities in the CHF rats.Conclusion:PZZS can improve the hemodynamic function,and alleviate the oxidative stress reaction in the CHF rat.     

Effects of ouabain on ultrastructure and function in rat heart

Objective：To investigate the ouabain＇s effects on the ultrastructure and function of the rat heart. Methods： Male Sprague-Dawley （SD） rats were treated with ouabain and systolic blood pressure （SBP） were recorded weekly. After 4 weeks, echocardiography was performed, hemodynamic parameters were measured by invasive cardiac catheterization and changes in heart ultrastructure were analyzed using transmission electron microscopy. Results：After treated by ouabain for 4 weeks, there were no significant differences in the mean SBP of the two groups. However, cardiac systolic and diastolic performances were both worsened with ouabain treatment by echocardiography, left ventricular chamber diameters and wall thickness were significantly increased in the rats of ouabain group. Invasive monitoring indicated that left ventricular systolic pressures （LVSP）, rate of pressure development （＋dp/dt） and rate of pressure decay （-dp/dt） were significantly attenuated and left ventricular end-diastolic pressures （LVEDP） were increased in ouabain group （P〈0. 05）. Disorganization of myofilaments, mitochondrial swelling, disruption and vacuolation, hyperplastic collagen fibers were found in ouabain group by transmission electron microscopy. Conclusion：It is suggested that ouabain induces alterations in cardiac ultrastructure and function, and the effects happened before the increase of blood pressure, which indicates that ouabain might damage rat heart independent of blood pressure.     

EFFECT OF AROTINOLOL ON LEFT VENTRICULAR FUNCTION IN PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY

Objective To evaluate the efficacy and safety of long-term treatment with arotinolol in patients with idiopathic dilated cardiomyopathy(IDCM).Methods Sixty-three patients with IDCM were evaluated at baseline and after 12-month therapy with arotinolol.The conventional therapy for congestive heart failure was continued throughout the study with arotinolol as the only β-blocker.Left ventricular function was assessed with the New York Heart Association functional class and two-dimensional echocardiography.Results After 12-month arotinolol treatment,there was a significant improvement in left ventricular systolic function.Left ventricular end-systolic dimension significantly decreased from 59.52±8.83 mm to 50.89±8.17 mm(P<0.001).Left ventricular ejection fraction significantly increased from 27.39%±7.94% to 41.13%±9.45%(P<0.001).Left ventricular mass index decreased from 150.47±42.42 g/m2 to 141.58±34.36 g/m2(P<0.01).No adverse events leading to premature discontinuation of study drug occurred.Conclusion In this preliminary study,12-month arotinolol treatment has a favorable effect on left ventricular function in patients with IDCM,and it is safe and well tolerated.     

Effect of ETA receptor antagonist BQ-123 on cardiac function and endothelin system after coronary microembolization in rats

Objective To evaluate the effects of BQ-123 on cardiac function and ventricular remodelling after coronary microembolization (CME) in rats. Methods We created a rat model of CME by injecting a suspension of autogenic microthrombotic particles into left ventricle. Three days after the procedure, the 30 surviving rats were randomly divided into 3 groups, each consisted of 10 rats: sham-operation group(SO), CME model group(CM) and BQ-123 intervention group(BQ). Rats in the BQ group received BQ-123 (400μg/kg per day, intraperitoneally) for 4 weeks. Plasma and myocardial endothelin-1 (ET-1) were measured by radioimmunoassay. And serial echocardiography was performed to monitor alterations of left ventricular end-systolic and end-diastolic diameter (LVESD, LVEED), and left ventricular short-axis fraction shortening(LVFS) and ejection fraction (LVEF), and physiologicography to document the changes of left ventricular systolic pressure (LVSP) and end-diastolic pressure pressure(LVEDP), and left ventricular maximum positive and negative dp/dt (±LVdp/dtmax). Results Compared with sham-operated group, both LVEDD and LVESD were increased (P<0.01), whereas LVFS and LVEF were significantly decreased (P<0.01) in CME group; LVEDP was markedly increased, while LVSP and±LVdp/ dtmax markedly reduced in CME group (P<0.01); plasma and tissue ET-1 levels increased in CME group (P<0.01). BQ-123 intervention significantly decreased both the plasma and tissue ET-1 levels (P<0.01), and markedly increased LVFS and LVEF, with significant improvement of LVSP and±LVdp/ dtmax (P<0.01). Conclusions Treatment with BQ-123 prevents ventricular remodeling after CME due to suppression of the endothelin system.     

Effects of electric stimulations applied during absolute refractory period on cardiac function of rabbits with heart failure

The effects of electric currents applied during absolute refractory period （ARP） on the cardiac function of rabbits with heart failure due to myocardial infarction （MI）, and the safety of this method were investigated. Thirty rabbits were randomly assigned equally to 3 groups： sham-operated group, LV-anterior wall cardiac contractility modulation （LV-CCM） group, and septum-CCM （S-CCM） group. A thoracotomy was performed on all the rabbits. Electric pulses were delivered during the ARP on the anterior wall of left ventricle in CCM group and in the septum in S-CCM group, respectively. The left ventricular systolic pressure （LVSP） and maximum positive left ventricular pressure change （＋dp/dtmax）, heart rates, ventricular tachycardia, ventricular fibrillation were observed. It was found that, as compared with the baseline, LVSP, and ＋dp/dtmax were significantly increased, on average, by 15.2% and 19.5% in LV-CCM group （P〈0,05）, and by 8.5% and 10.8% in S-CCM group （P〈0.05）. LVEDP was significantly decreased and -dp/dtmx increased both in LV-CCM group and S-CCM group （P〈0.05）. CCM had no effect on heart rate and induced no arrhythmia in short time. It is concluded that electric currents delivered during the ARP could significantly enhance the contractility of myocardium safely, suggesting that CCM stimulation is a novel potent method for contractility modulation.     

Impact of 1, 25-(OH)2D3 on Left Ventricular Hypertrophy in Type 2 Diabetic Rats

Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy (LVH) in type 2 diabetic rats.
Methods Type 2 diabetic mellitus (DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy (LVH) by ultrasound examination, and randomly assigned into three groups:untreated (DM-LVH, n=7), treated with insulin (DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3 (DM-LVH+VD, n=6). Healthy male rats were used as the controls group (n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later.
Results In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group (P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased (all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group (P<0.05), whereas the other parameters were significantly decreased (all P<0.05).
Conclusion 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.     

Mechanism and Correlated Factors of SAM Phenomenon after Aortic Valve Replacement

To investigate the mechanism and correlated factors of systolic anterior motion (SAM) phenomenon after aortic valve replacement, 48 patients with severe aortic valvular stenosis were studied. Tested by echo-Doppler one week after aortic valve replacement, the patients were divided into two groups: SAM group and non-SAM group. The data of the left ventricular end-diastolic di-ameters, the left ventricular end-systolic diameters, the left ventricular outflow diameters, the thick-ness of the interventricular septum, the posterior wall of left ventricle, the blood velocities of left ventricular outflow and intra-cavitary gradients were recorded and compared. The results showed that no patients died during or after the operation. The blood velocities of left ventricular outflow was in-creased significantly in 9 patients (>2.5 m/s), and 6 of them developed SAM phenomenon. There was significant difference in all indexes (P<0.05 or P<0.01) except the posterior wall of left ventricle (P>0.05) between two groups. These indicated that the present of SAM phenomenon after aortic valve replacement may be directly related to the increase of blood velocities of left ventricular out-flow and intra-cavitary gradients. It is also suggested that smaller left ventricular diastolic diameters, left ventricular systolic diameters, left ventricular outflow diameters and hypertrophy of interven-tricular septum may be the anatomy basis of SAM phenomenon.     

Shenfu Injection(参附注射液) Suppresses Inflammation by Targeting Haptoglobin and Pentraxin 3 in Rats with Chronic Ischemic Heart Failure

Objective:To investigate the regulatory effects of Shenfu Injection(SFI,参附注射液) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure(CHF).Methods:Forty-five healthy Wistar rats were randomized into three groups:sham,heart failure(model) and SFI group.The CHF was induced by left coronary artery ligation.Seven days after the surgical operation,animals in the sham group and the model group received saline(6.2 mL/kg/d),while animals in the SFI group received SFI(6.2 mL/kg·d) intraperitoneally.Four weeks later,cardiac hemodynamic parameters were measured via the carotid route.The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrixassisted laser desorption/ionization time-of-flight mass spectrometer(MALDI-TOF MS).Results:Recording of hemodynamic parameters showed that left ventricular systolic pressure(LVSP),maximum rate of left ventricular pressure(+dp/dt_(max)) rise,and maximum rate of left ventricular pressure(-dp/dt_(max)) decrease,while the left ventricular end diastolic pressure(LVEDP) rose in the model group compared to those in the sham group(P0.05).The results of the MALDI-TOF MS indicated that haptoglobin(HP),pentraxin 3(PTX3) and alpha-1-antitrypsin were up-regulated,while serum albumin and 40 S ribosomal protein were down-regulated in the model group(P0.05).Compared with the model group,LVSP,+dp/dt_(max)and-dp/dt_(max) were higher,while LVEDP was lower in the SFI group(P0.05).Expression levels of HP and PTX3 were lower than in the model group(P0.05).Conclusion:SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF.The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure,and they could also be the serum protein targets of SFI.     

Improvement in cardiac function after sarcoplasmic reticulum Ca2+-ATPase gene transfer in a beagle heart failure model

Background Heart failure （HF） is a major cause of morbidity and mortality worldwide, but current treatment modalities cannot reverse the underlying pathological state of the heart. Gene-based therapies are emerging as promising therapeutic modalities in HF patients. Our previous studies have shown that recombinant adeno-associated viral （rAAV） gene transfer of Sarco-endoplasmic reticulum calcium ATPase （SERCA2a） can be effective in treating rats with chronic heart failure （CHF）. The aim of this study was to examine the effects of SERCA2a gene transfer in a large HF animal model. Methods HF was induced in beagles by rapid right ventricular pacing （230 beats/min） for 30 days. A reduced rate ventricular pacing （180 beats/min） was continued for another 30 days. The beagles were assigned to four groups： （a） control group （n=4）; （b） HF group （n=4）; （c） enhanced green fluorescent protein group （n=4）; and （d） SERCA2a group （n=4）. rAAV1-EGFP （1×10^12 μg） and rAAV1-SERCA2a （1×10^12 μg） were delivered intramyocardially. SERCA2a expression was assessed by Western blotting and immunohistochemistry. Results Following 30 days of SERCA2a gene transfer in HF beagles its protein expression was significantly higher than in the HF group than in the control group （P 〈0.05）. Heart function improved along with the increase in SERCA2a expression. Left ventricular systolic function significantly improved, including the ejection fraction, left ventricular systolic pressure, maximal rate of rise of left ventricular pressure （＋dp/dtmax）, and the maximal rate of decline of left ventricular pressure （-dp/dtmax） （P 〈0.05）. Left ventricular end-diastole pressure significantly decreased （P 〈0.05）. The expression of SERCA2a in the myocardial tissue was higher in the SERCA2a group than in the HF group （P〈0.05）. Conclusions Intramyocardial injection of rAAV1-SERCA2a can improve the cardiac function in beagles induced with HE We expect further studies on SERCA2a＇s long-term safety, efficacy, dosage and the optimization before using it in humans with HF.     

Beneficial effects of berberine on hemodynamics during acute ischemic left ventricular failure in dogs.

In 18 dogs ischemic left ventricular failure characterized by a 30 percent reduction in peak rate of rise of left ventricular pressure (+dp/dt) and elevation of left ventricular end-diastolic pressure (LVEDP) to 15 mmHg or more was produced by ligation of the proximal left anterior descending coronary artery followed by serial occlusions of the distal left circumflex coronary artery. In 10 days, administration of berberine in an intravenous bolus injection (1 mg/kg, within 3 minutes) followed by a constant infusion (0.2 mg/kg/min, 30 minutes) increased the cardiac output (CO) from 1.25 +/- 0.12 to 1.61 +/- 0.17 L/min (P < 0.05), and +dp/dt from 810 +/- 85 to 1021 +/- 130 mmHg/s (P < 0.01), and decreased LVEDP from 16.5 +/- 1.3 to 12.0 +/- 1.0 mmHg (P < 0.05), diastolic blood pressure from 94 +/- 6 to 84 +/- 5 mmHg (P < 0.01), systemic vascular resistance from 7303 +/- 278 to 5442 +/- 231 dynes.x/cm5 (P < 0.01), but did not affect the heart rate. Injection of 5% glucose with the same volume did not improve CO and dp/dt (P > 0.05) but increased the LVEDP from 17.1 +/- 1.4 to 17.8 +/- 1.6 mmHg (P < 0.01) in 8 dogs. The levels of plasma concentration of berberine was determined with high-performance liquid chromatography. The changes in plasma drug level were found parallel to hemodynamic effects of berberine. The results of this study showed that berberine was able to improve the impaired left ventricular function by its positive inotropic effect and mild systemic vasodilatation.