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.     

Speckle Tracking Echocardiography Assessment of Global and Regional Contraction Dysfunction in the Mice Model of Pressure Overload

Speckle tracking echocardiography(STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge(G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group(n=10), mild trans-aortic banding(TAB) group(n=14) and severe TAB group(n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening(FS), left ventricular(LV) mass, and left ventricular end diastolic diameter(LVEDD)(P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures(P>0.05 for both). STE analysis revealed that longitudinal strain(LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups(P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group(P<0.05). Radial strain(RS) and circumferential strain(CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group(P<0.05 for both) from the postoperative week 1(P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6(P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.     

Comparison of Shenfu Injection(参附注射液) and Epinephrine on Catecholamine Levels in A Porcine Model of Prolonged Cardiac Arrest

Objective:To compare the effects of Shenfu Injection(SFI) and epinephrine(EPI) on catecholamine levels in a porcine model of prolonged cardiac arrest(CA).Methods:After 8 min of untreated ventricular fibrillation,24 Wuzhishan miniature pigs were randomly assigned to one of the three groups(n=8 per group) and received central venous injection,respectively:SFI group(1 mL/kg),EPI group(20 μg/kg EPI),and normal saline(NS) group.Cardiac output(CO),maximum rate of increase/decrease in left ventricular pressure(±dp/dt),serum levels of EPI,norepinephrine(NE),and dopamine(DA) were determined at baseline and at 0.5,1,2,and 4 h after restoration of spontaneous circulation.Results:The duration of cardiopulmonary resuscitation was shorter in the EPI and SFI groups than in the NS group(P0.05).The EPI level increased significantly after restoration of spontaneous circulation(ROSC) in all three groups,and was significantly different between the EPI group and the other two groups immediately after ROSC(both P0.01),but these differences gradually disappeared over time.There were no significant differences in NE or DA levels among the three groups,and there were no correlations between catecholamine levels and CO or dp/dt(P0.05).Conclusions:SFI did not significantly affect endogenous catecholamine levels during cardiopulmonary resuscitation after prolonged ventricular fibrillation.However,SFI improved oxygen metabolism,and produced a better hemodynamic status compared with EPI.SFI might be a potentially vasopressor drug for the treatment of CA.     

Comparison of epinephrine and Shen-Fu injection on resuscitation outcomes in a porcine model of prolonged cardiac arrest

Background Epinephrine has been used as a first-choice vasopressor drug for cardiac arrest （CA） since 1974.However,the administration of epinephrine is controversial.This study aims to compare the effects of Shen-Fu injection （SFI） and epinephrine on resuscitation outcomes in a porcine model of prolonged CA.Methods Ventricular fibrillation （VF） was electrically induced.After 8 minutes of untreated VF and 2 minutes of chest compressions,24 pigs were randomly divided into 3 groups （n=8 per group）：central venous injection of SFI （SFI group）,epinephrine （EPI group）,or saline solution （SA group）.The haemodynamic status and oxygen metabolism parameters,including cardiac output,mean arterial pressure,left ventricular dp/dtmax and negative dp/dtmax,oxygen delivery （DO2）,and oxygen consumption （VO2）,were calculated.Results SFI shortened the time to restoration of spontaneous circulation （ROSC） and decreased the number of shocks,similar to epinephrine.However,the mean arterial pressure,cardiac output,left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the EPI group at 4 and 6 hours after ROSC.VO2 and ERO2 decreased after ROSC and then increased.VO2 and ERO2 were significantly higher in the SFI group than in the EPI and SA groups after ROSC,while those were lowest in the EPI group among all groups.Conclusions SFI shortened the time to ROSC and decreased the number of shocks,similar to epinephrine.However,SFI improved oxygen metabolism,and produced a better hemodynamic status compared with epinephrine.SFI might be a potentially vasopressor drug for the treatment of CA.     

Shen-Fu Injection(参附注射液) Alleviates Post-resuscitation Myocardial Dysfunction by Up-regulating Expression of Sarcoplasmic Reticulum Ca2~+ -ATPase

Objective: To compare the effect of Shen-Fu Injection(SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca2~+ ATPase 2a(SERCA2a) in a pig model with post-resuscitation myocardial dysfunction. Methods: Ventricular fibrillation(VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation(CPR), all animals were randomly administered a bolus injection of saline placebo(SA group, n=10), SFI(0.8 mg/kg, SFI group, n=10) or epinephrine(20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation(ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase(AC), cyclic adenosine monophosphate(c AMP) and the expressions of β1-adrenoceptor(AR) and SERCA 2a were determined. Results: Cardiac output, left ventricular dp/dt_(max) and negative dp/dt_(max) were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2 a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups(P0.05 or P0.01). Conclusions: The administration of epinephrine during CPR decreased the expression of SERCA2 a and aggravated postresuscitation myocardial function(P0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2 a expression.     

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.     

Recombinant human growth hormone secreted from tissue-engineered bioartificial muscle improves left ventricular function in rat with acute myocardial infarction

Background Experimental studies and preliminary clinical studies have suggested that growth hormone （GH） treatment may improve cardiovascular parameters in chronic heart failure （CHF）. Recombinant human GH （rhGH） has been delivered by a recombinant protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. The present study aimed to examine a new method for delivery of rhGH using genetically modified bioartificial muscles （BAMs）, and investigate whether the rhGH delivered by this technique improves left ventricular （LV） function in rats with CHE Methods Primary skeletal myoblasts were isolated from several Sprague-Dawley （SD） rats, cultured, purified, and retrovirally transduced to synthesize and secrete human rhGH, and tissue-engineered into implantable BAMs. Ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 2 groups： CHF control group （n=6） and CHF treatment group （n=6）. The CHF control group received non-rhGH-secreting BAM （GFP-BAMs） transplantation, and the CHF treatment group received rhGH-secreting BAM （GH-BAMs） transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups： sham control group （n=6） and sham treatment group （n=6）. The sham control group underwent GFP-BAM transplantation, and the sham treatment group underwent GH-BAM transplantation. GH-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats with ligation of the left coronary artery or sham operation was performed. Eight weeks after the treatment, echocardiography was performed, hGH, insulin-like growth factor-1 （IGF-1） and TNF-a levels in rat serum were measured by radioimmunoassay and ELISA, and then the rats were killed and ventricular samples were subjected to immunohistochemistry. Results Primary rat myoblasts were retrovirally transduced to secrete rhGH and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted 1 to 2 lug of bioactive rhGH per day. When implanted into syngeneic rat, GH-BAMs secreted and delivered rhGH. Eight weeks after therapy, LV ejection fraction （EF） and fractional shortening （FS） were significantly higher in CHF rats treated with GH-BAMs than in those treated with GFP-BAMs （（65.0i-6.5）% vs （48.1±6.8）%, P 〈0.05）, （（41.3±7.4）% VS （26.5±7.1）%, P 〈0.05）. LV end-diastolic dimension （LVEDD） was significantly lower in CHF rats treated with GH-BAM than in CHF rats treated with GFP-BAM （P 〈0.05）. The levels of serum GH and IGF-1 were increased significantly in both CHF and sham rats treated with GH-BAM. The level of serum TNF-α decreased more significantly in the CHF treatment group than in the CHF control group.Conclusions rhGH significantly improves LV function and prevents cardiac remodeling in rats with CHF. Genetically modified tissue-engineered bioartificial muscle provides a method delivering recombinant protein for the treatment of heart failure.     

Effect of Yiqi Huoxue Recipe (益气活血方) on cardiac function and ultrastructure in regression of pressure overload-induced myocardial hypertrophy in rats

Objective:To investigate the effect of Yiqi Huoxue Recipe (YHR,益气活血方)on the cardiac function and ultrastructure during the regression of myocardial hypertrophy induced by pressure overload in rats.Methods:The model of myocardial hypertrophy was established by abdominal aortic banding.Eighty male Wistar rats were divided into six groups,the normal control groupⅠ(n=20),the normal control groupⅡ(n=12),the hypertension model groupⅠ(n=12),the hypertension model groupⅡ(n=12),the YHR group(n=12)and the Captopril group(n=12).The observation was carried out in the normal control groupⅠand the hypertension model groupⅠafter 4 weeks of modeling,and the other four groups were observed after 16 weeks of modeling(12 weeks of administration).The cardiac function was measured with a multichannel biological signal analysis system,and the myocardium ultrastructure was observed by a transmission electron microscope. Results:(1)Compared with the normal control groupⅠ,the systolic blood pressure and cardiac coefficient(left ventricular weight/body weight)in the modelⅠgroup was higher(P<0.05,P<0.01). (2)In the YHR group,cardiac coefficient and-dp/dt_(max)were lower,left ventricular systolic pressure and dp/dt_(min)were higher when compared with the model groupⅡand the Captopril group(P<0.05 or P<0.01).In the Captopril group,only cardiac coefficient was lower when compared with the mode groupⅡ(P<0.05).(3)Compared with the normal control groupⅡ, dp/dt_(max)was higher(P<0.01), -dp/dt_(max)and isovolumetric contraction time(ICT)was lower(P<0.05,P<0.01)in both the YHR group and the Captopril group.(4)Results of the myocardium ultrastructure showed edema under myocardium plasmalemma,enlarged sarcoplasmic reticulum and T tube,and significantly enlarged intercalated disc of the cardiac muscle in the model groups.In the Captopril group,the extension of sarcoplasmic reticulum and T tube as well as the pathological changes of intercalated disc were lighter,with slight edema under the myocardium plasmalemma.In the YHR group,the expansion of the sarcoplasmic reticulum was less than in the Captopril group,part of the pathological changes of intercalated discs was slightly more severe than that in the Captopril group,the dissolution of nuclear chromatin was not found,which was similar to that of the Captopril group,and no injury of the nucleus was found,either.Conclusion:YHR could reverse myocardial hypertrophy in rats with abdominal aortic banding and improve the systolic and diastolic function of the left ventricle.The ultrastructure of the myocardium such as arcoplasmic reticulum,intercalated disc,and cell nucleus in abdominal aortic banding rats could be partly reversed by the recipe.     

MICROCOMPUTER DATA PROCESSING OF HEMODYNAMIC EFFECTS OF A CARDIOTOXIC FRACTION(Fr.19-2) FROM THE SOUTHERN CHINESE COBRA(NAJA NAJA ATRA CANTOR)IN ANESTHETIZED CATS

A new program of microcomputer data processing was developed on AppleIIe computer on-line with 8-ch polygraph in the study of hemodynamic effects of a cardiotoxic fraction (Fr. 19-2) from the southern Chinese cobra (Naja naja atra Cantor). In anesthetized open-chest cats, Fr. 19-2 caused a dose-related decrease in various indices of myocardial contractility and pumping function such as dp/dt_(max), V_(CE-DP40), V_(CE-CPIP),V_(pm), CO, CI, SV, SI, LVW, LVWI, LVSW and LVSWI. It reduced the heart rate without other cardiac arrhythmias. A marked decrease in -dp/dt_(max) (219.7±23.5 vs 110.5±29.1kPa/s, P<0.01) and an increase in time constant of the fall of left ventricular pressure during isovolumetric relaxation (T) was induced. LVEDP rised till the dose of Fr. 19-2 reached 0.4mg/kg. It is concluded that this cardiotoxic fraction predominantly inhibits the hemodynamic indices and myocardial performance. With the new microcomputer data real-time processing system, 33 elaborated hemodynamic indices were ca     

Granulocyte-macrophage colony stimulating factor improves cardiac function in rabbits following myocardial infarction

To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the ani-mals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10μg/kg/day, once a day for 5 days.The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct re-gion of the heart were also studied. Restflts: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dys-function shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificanfly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic mvocardium.     

Effect of Atorvastatin on Serum MMP-2,MMP-9 and TIMP-1 in Rabbits with Chronic Heart Failure

Objective: To observe the effects of atorvastatin on serum matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), and the tissue inhibitor of metalloproteinase-1(TIMP-1) in the development of chronic heart failure. To investigate the role of atorvastatin in the therapy of chronic heart failure and determine its possible mechanism of action. Methods: Thirty Japanese Big Ear rabbits were randomly selected and divided into 3 groups: sham-operated group(SO group), heart failure control group(HC group) and heart failure atorvastatin therapy group(HA group), with 6, 12 and 12 animals in the respective groups. Volume overloading was produced in the HC group and HA group animals by creating an aortic insufficiency, induced by damaging the aortic valve with a catheter introduced through the carotid artery. After 14 days, abdominal aorta constriction was performed in order to obtain a pressure overload. Six weeks later rabbits in the HA group were administered atorvastatin 3mg. Kg-1.d-1 for 4 weeks, at which time the experiment was terminated. Arterial blood was drawn and serum levels of MMP-2, MMP-9 and TIMP-1 were measured in all groups at the same time using an ELISA method. Results: Structural and functional indicators of chronic heart failure(CHF) were seen in both the HC and HA groups, but atorvastatin significantly reduced the observed effects. The serum concentrations of MMP-2, MMP-9 and TIMP-1 were at low levels in all three groups at the start of the study, with no difference between them(P < 0.05). At the end of 6th week concentrations were significantly increased in the HC and HA groups compared with the SO group(P < 0.05), but there were no differences between the HC group and HA group(P > 0.05). The increased concentrations in HC group continued to the end of the experiment, but values in the HA group were all lower than those in the HC group by the end of the experiment(P < 0.05). Conclusion: Serum concentrations of MMP-2, MMP-9 and TIMP-1 increase significantly during the course of CHF, paralleling the pathological progress of CHF. Atorvastatin benefits CHF, and the decreased serum levels of MMP-2, MMP- 9 and TIMP-1 may be one of the drug's mechanism of action.     

Cardioprotection of Shenfu Injection (参附注射液) against myocardial ischemia/reperfusion injury in open heart surgery

Objective: To investigate the protective effect of Shenfu Injection (参附注射液, SFI) against myocardium ischemia/reperfusion injury (IRI) in rnitral valve replacement (MVR) with cardiopulmonary bypass (CPB). Methods: Forty patients undergoing selective MVR were randomly assigned to the control group and trial Groups ⅠⅡ,Ⅲ, and Ⅳ according to the different administrations of SFI, 8 patients in each group. The changes of systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) in each group were monitored, respectively. The recovering percentage of spontaneous heart beat, the heart rate (HR) and cardiac rhythm as well as the abnormal duration of ECG-ST segment were recorded after the restoration of heart beat. The serum concentration of cardiac troponin Ⅰ (cTnl), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were determined as well. Results: (1) The SBP, MBP and DBP values, the recovering rate of spontaneous heart beat, HR, ECG-ST, atrioventricular block and ventricular arrhythmia were significantly improved in group Ⅳ compared with any other groups. (2) Compared with the control group, the postoperative serum contents of cTnl and MDA were significantly decreased, but the activity of SOD was significantly increased in group Ⅳ. Conclusions: SFI had a certain protective effect against myocardium IRI. Moreover, better efficacy was seen with the administration of 1.5 mL/kg SFI into CPB priming fluid and pumping 1.5 mL/kg SFI via CPB as soon as the clamped aorta was unclamped.     

Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Objective:To compare the cardioprotective efficacy of equimolar doses(50 mM/kg,p.o.)of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats.Methods:Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg.This study included four treatment groups of rats(n=6):the control group(0.5%carboxymethyl cellulose solution-treated),the doxorubicin-treated group(0.5%carboxymethyl cellulose solution along with doxorubicin),the genistein-treated group(50 mM/kg/day;p.o.along with doxorubicin)and phloretin-treated group(50 mM/kg/day;p.o.along with doxorubicin).On the 10th day of dosing,rats were anesthetized for recording ECG,mean arterial pressure,and left ventricular function.Oxidative stress,nitric oxide levels,and inflammatory cytokines were estimated in the cardiac tissue.Cardiac function parameters(creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase)were estimated in the serum samples.Results:Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats.Phloretin administration attenuated doxorubicin-induced alterations in hemodynamic parameters(heart rate,mean arterial blood pressure,and left ventricular function)and suppressed the expression of pro-inflammatory cytokines.The cardiac injury markers like creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase were reduced by both genistein and phloretin.All these effects of phloretin were more prominent than genistein.Conclusions:Phloretin offers cardioprotection that is comparable to genistein,a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity.Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.     

Effect of Shen-Fu Injection(参附注射液)on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients

Objective: To investigate the hemodynamic effect of Shen-Fu Injection(参附注射液, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output(PICCO). Methods: All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1 st, 2014 to December 31 th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group(33 cases) and control group(32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. Results: The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h(P0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group(P0.05), including cardiac index(CI), global end diastolic volume index(GEDI), mean arterial pressure(MAP) and heart rate(HR). In addition, there was no significant change of extra-vascular lung water index between the two groups(P0.05). Conclusion: SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.     

Alterations in myosin heavy chain isoform gene expression during the transition from compensatory hypertrophy to congestive heart failure in rats

Objective To explore the molecular mechanism underlying the decreased velocity of tension rise in rat myocardium during congestive heart failure (CHF) and left ventricula r hypertrophy (LVH) induced by aortic stenosis.Methods The maximum velocity of tension rise (+dT/dt(max)) was measured in left ventricular papillary muscle and the mRNA level of myosin heavy chain (MHC) isof orms in the left ventricle were detected by Northern blot analysis.Results The value of +dT/dt(max) in CHF and LVH group were 64.17% and 37.15% lower than sham-operated controls (Sham) (P&lt;0.01); values in the CHF group were 42.99% lower than that of LVH (P&lt;0.01). The level of α-MHC mRNA in LVH was not different from that of the Sham (P&gt;0.05), but decreased significan tly in CHF to 42.3% of Sham and 56.1% of LVH (P&lt;0.01). The level of β- MHC mRNA was up-regulated by 88.3% (P&lt;0.01) in LVH compared with Sham and the level of β-MHC in CHF was 1.5-fold and 3.7-fold higher than that in L VH and Sham respectively (P&lt;0.01). The ratio of α-MHC/β-MHC mRNA in LV H and CHF decreased to 42.4% and 9.8% respectively of the value in Sham (P &lt;0.01). Correlation between α-MHC/β-MHC mRNA level and +dT/dt(max) wa s analyzed which showed that these values were positively correlated with a corr elation coefficient of 0.875 (P&lt;0.01).Conclusion The decreased ratio of α-MHC/β-MHC mRNA was the major molecular mechanism un derlying the decreased +dT/dt(max) in CHF and LVH myocardium. The decreased ratio of α-MHC/β-MHC mRNA in LVH was mainly due to the up regulation of β-MHC mRNA while in CHF both down regulation of α-MHC and up regulatio n of β-MHC were involved.     

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.     

Chronic blocking of β3-adrenoceptor ameliorates cardiac function in rat model of heart failure

Background Stimulation of the heart β(3)-adrenoceptor (AR) may result in a negative inotropic effect. Being up-regulated, β(3)-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of β(3)-AR on heart failure has not been fully elucidated. In this study, we used a selective β(3)-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism.Methods Male Wistar rats were chosen randomly as controls (n=8). Isoproterenol induced heart failure rats were randomly divided into ISO group (n=10) and SR group (n=10). The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes: the ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW), collagen volume fraction (CVF), left ventricular end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVESd), ejection fraction (EF), fractional shortening (FS) and the ratio of E wave to A wave (E/A),the mRNA and protein expression of β(3)-AR and eNOS, and cGMP level in the heart.Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group (P&lt;0.01), but they were limited in the SR group (P&lt;0.05 compared with the ISO group). CVF increased in the ISO group and the SR group (P&lt;0.01), but it was significantly attenuated in the SR group (P&lt;0.01). LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group (P&lt;0.01), while EF and FS were significantly decreased (P&lt;0.01). Compared with the ISO group, the SR group showed that LVEDd, LVESd and E/A ratio were significantly decreased (P&lt;0.01), whereas EF and FS were significantly increased (P&lt;0.01). β(3)-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P&lt;0.01). These increases were all attenuated in the SR group compared with the ISO group (P&lt;0.01). The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group (P&lt;0.01), whereas SR59230A treatment normalized this increment (P&lt;0.01).Conclusions Chronic blocking of β(3)-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.