Network pharmacology and subsequent experimental validation reveal the synergistic myocardial protection mechanism of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.

Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and subsequent experimental validation.Methods:Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of s.miltiorrhiza and C.tinctorius as herb pair.Molecular docking was used to verify the binding of the components of these herbs and their potential targets.An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects,which were evaluated using the combination index.Western blot was performed to detect the protein expression of these targets.Results:Network pharmacology analysis revealed 5 pathways and 8 core targets of s.miltiorrhiza and C.tinctorius in myocardial protection.Five of the core targets were enriched in the hypoxia-inducible factor-1(HIF-1)signaling pathway.S.miltiorrhiza-C.tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway.As an upstream gene of the HIF-1 pathway,STAT3 can be activated by the active ingredients cryptotanshinone(Ctan),salvianolic acid B(Sal.B),and myricetin(Myric).Cell experiments revealed that Myric,Sal.B,and Ctan also exhibited synergistic myocardial protective activity.Molecular docking verified the strong binding of Myric,Sal.B,and Ctan to STAT3.Western blot further showed that the active ingredients synergistically upregulated the protein expressionof STAT3.Conclusion:The pharmacodynamic transmission analysis revealed that the active ingredients of S.miltiorrhiza and C.tinctorius can synergistically resist ischemia through various targets and pathways.This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

Sevoflurane Versus Propofol for Myocardial Protection in Patients Undergoing Coronary Artery Bypass Grafting Surgery: a Meta-analysis of Randomized Controlled Trials

Objective To systematically review randomized controlled trials to compare myocardial protection profiles of sevoflurane with propofol in patients undergoing coronary artery bypass grafting （CABG） surgery. Methods Electronic databases were searched to identify all randomized controlled trials comparing sevoflurane with propofol for protecting myocardium in adult patients undergoing CABG surgery. Two authors independently extracted patients＇ perioperative data, including patients＇ baseline characteristics, surgical variables, and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference （WMD） and 95% confidential interval （C/）. For dichotomous data, treatment effects were calculated as odds ratio （OR） and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity （Q test P〈0.05）. Sensitivity analyses were done by examining the influence of statistical model on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P〈0.05. Results Our search yielded 13 studies including 696 patients, and 402 patients were allocated into sevoflurane group and 294 into propofol group. There was no significant difference in postoperative mechanical ventilation time, inotropic support, mortality, myocardial infarction, and atrial fibrillation between the two groups （all P〉0.05）. Patients randomized into sevoflurane group had higher post-bypass cardiac index （WMD=0.39, 95% CI： 0.18 to 0.60, P=0.0003）, lower troponin I level （WMD=-0.82, 95% CI：-0.87 to -0.85, P=0.0002）, lower incidence of myocardial ischemia （OR=0.37, 95% CI： 0.16 to 0.83, P=0.02）, shorter ICU and hospital stay length （WMD=-10.99, 95% CI： -12.97 to -9.01, P〈0.00001; WMD=-0.78, 95% CI： -1.00 to -0.56, P〈0.00001, respectively）. Conclusion This meta-analysis has found some evidence showing that sevoflurane has better myocardial protection than propofol in CABG surgery.

Effects of Warm Blood Cardioplegic Solution on Myocardial Protection

To evaluate the effects of warm blood cardioplegic solution on myocardial protection, normothermic induction and terminal perfusion of oxygenated blood cardioplegia in combination with intermittent administration of cold blood cardioplegia during ischemia were studied in an isolated working rat heart model.The experimental protocol consisted of a 120 min cardioplegic arrest followed by 45 min normothermic reperfusion. Myocardial content of adenosine triphosphate (ATP), recovery of the left ventricular function, release of creatine phosphokinase (CPK) and ultrastructure of myocardium were assessed before and after ischemia. The results showed that the hearts preserved with warm blood cardioplegic induction and terminal perfusion had significantly higher levels of ATP,better recovery of cardiac function and lower releases of CPK than those receiving cold blood cardioplegia alone, with myocardial tissue being of generally normal structure. These findings suggest that warm induction and terminal perfusion of blood cardioplegic solution can accelerate myocardial metabolic and functional recovery, preserve high-energy phosphate, reduce myocardial injury and enhance myocardial protection.

Experimental and Clinical Research of Myocardial Protection Effect Using MHBC Perfusion

Objectives To determine themyocardium -protecting effect of medium hypothermalblood cardioplegia (MHBC); further demonstrates thatthe optimal temperature between these hypothermaland normothermic can overcome the disadvantages;and thus discovers a more effective myocardium pro-tecting method. Methods Section 1: 14 mongreldogs (15-20 kg) were randomly divided into twogroups: experimental group and control group; car-dialpulmonary bypass was conventionally instituted,moderate hypothermia blood cardioplegia was used inexperimental group, Blood samples from right atriumtaken for examination of lactate dehydrogenase (LDH)creatine kinase(CK-MB) and Topin Ⅰ(cTn-Ⅰ). speci-mens of left ventricular subendocardial myocardiumwere biopsied to observe changes of ultrastructure.Section 2: 24 patients were randomly divided into twogroups and both groups received two types of treat-ment (same as Section 1) after aorta cross-clamp(ACC). Biochemical index and Clinical observationwere caculated as the indicators. Results In the ex-perimental research, LDH, CK-MB, cTn-Ⅰ were foundincreased afer reperfusion in both groups, but the ex-tent of changes in experimental group is tiny (statisti-cal difference). Compared with control group the effectof MHBC on cardial function is litile; the ultrastruc-ture. of cardiac muscle has no obvious change. In theclinical research, compared the test results of venousblood drawn before CPB, after beating recovery andafter CPB, CBC perfused group (LDH, CK-MB leak-age and cTn-Ⅰ value increase.) compared with MHBCperfused group had no remarkable difference (P>0.05), but at the result of clinical observation: MHBCperfused group had red, soft hearts after cardiac arrestbut CBC perfused group had pale, spasmatic heartsafter cardiac arrest; 0 case in MHBC perfused groupand 3 cases in CBC perfused group had twitch-re-moving beat recovery; 11 cases in MHBC perfusedgroup and 3 cases in CBC perfused group recoveredsinus heart rhythm after surgery; average consumptionof lidocaine was 16.67 (±55.28) mg for MHBC per-fused group and 118.33(±82.65) mg for CBC perfusedgroup (P<0.01) afer surgery; 4 cases in MHBC per-fused group and 11 cases in CBC perfused group suf-fered arrhythmia after surgery. Conclusions As anew myocardium - protecting method, MHBC perfusionin combination with natural body temperature drop ofCPB is worth clinical dissemination and application.

Efficacy of electroacupuncture on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass:a systematic review and Meta-analysis

OBJECTIVE:To evaluate the efficacy of electroacupuncture(EA)intervention on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass(CPB).METHODS:Eight databases,including Pub Med,Embase,the Cochrane Library,Web of Science,Chinese Bio Medical Literature Database,China National Knowledge Infrastructure Database,Wanfang Data,China Science and Technology Journal Database,and two clinical trial registries,were searched.All randomized controlled trials(RCTs)related to EA intervention in cardiac surgery with CPB were collected.Based on the inclusion and exclusion criteria,two researchers independently screened articles and extracted data.After the quality evaluation,RevMan 5.3 software was used for analysis.RESULTS:Fourteen RCTs involving 836 patients were included.Compared with the control treatment,EA significantly increased the incidence of cardiac automatic rebeat after aortic unclamping[relative risk(RR)=1.15,95%confidence interval(CI)(1.01,1.31),P<0.05;moderate].Twenty-four hours after aortic unclamping,EA significantly increased the superoxide dismutase[standardized mean difference(SMD)=0.96,95%CI(0.32,1.61),P<0.05;low],and interleukin(IL)-2[SMD=1.33,95%CI(0.19,2.47),P<0.05;very low]expression levels and decreased the malondialdehyde[SMD=-1.62,95%CI(-2.15,-1.09),P<0.05;moderate],tumour necrosis factor-α[SMD=-1.28,95%CI(-2.37,-0.19),P<0.05;moderate],and cardiac troponin I[SMD=-1.09,95%CI(-1.85,-0.32),P<0.05;low]expression levels as well as the inotrope scores[SMD=-0.77,95%CI(-1.22,-0.31),P<0.05;high].There was no difference in IL-6 and IL-10 expression levels.The amount of intraoperative sedative[SMD=-0.31,95%CI(-0.54,-0.09),P<0.05;moderate]and opioid analgesic[SMD=-0.96,95%CI(-1.53,-0.38),P<0.05;low]medication was significantly lower in the EA group than in the control group.Moreover,the postoperative tracheal intubation time[SMD=-0.92,95%CI(-1.40,-0.45),P<0.05;low]and intensive care unit stay[SMD=-1.71,95%CI(-3.06,-0.36),P<0.05;low]were significantly shorter in the EA group than in the control group.There were no differences in the time to get out of bed for the first time,total days of antibiotic use after surgery,or postoperative hospital stay.No adverse reactions related to EA were reported in any of the included studies.CONCLUSIONS:In cardiac surgery with CPB,EA may be a safe and effective strategy to reduce myocardial ischaemia-reperfusion injury and speed up the recovery of patients after surgery.These findings must be interpreted with caution,as most of the evidence was of low or moderate quality.More RCTs with larger sample sizes and higher quality are needed to provide more convincing evidence.

Myocardial protection of immature rabbits with an ATP-sensitive K^+ channel opener pinacidil

Objective To investigate the effectiveness of pinacidil,an opener of ATP-sensitive K+ channels,in protecting the myocardium of immature rabbit hearts from ischemic reperfusion injury.Methods Rabbit hearts underwent 30 min of global normothermic ischemia followed by 30 min of reperfusion on the modified Langendorff apparatus.Fifty-two isolated hearts of 3 - 4 week-old immature rabbits were divided into 4 groups randomly.During ischemia,3 different cardioplegic solutions were administered intermittently by infusion every 15 min(20-25 mi each time in all groups).Group 1:control group(n = 13);group 2:Krebs-Henseleit(K-H)solution with potassium(16 mmol/L)(n = 1:3);group 3:K-H solution with potassium(16 mmol/L)and pinacidil(50 μmol/L)(n = 13);group 4:K-H solution with potassium(16 mmol/L),pinacidil(50 μmol/L)and glibenclamide(10 μmol/L)(n = 13).The pre-ischemic and post-ischemic myocardial functions were assessed by the percentage recovery of the left ventricular developed pressure(LVDP);the left ventricular end-diastolic pressure(LVEDP);both the Positive peak and negative peaks of the first derivative of the left ventricular pressures(± dp/dtmax);coronary flow;the level of creatine kinase(CK),lactic dehydrogenase(LDH)and aspartate transcarbamoylase(AST)in coronary sinus venous effluent;and by myocardial ultrastructural changes.Results Before myocardial ischemia,there were no significant differences among the four groups in any of the parameters mentioned above.Post-ischemic recovery of LVDP,LVEDP,± dp/dtmax,coronary flow,the level of CK,LDH and AST,and myocardial ultrastructural changes were better in group 3 than those in the three other groups.Conclusions As a new and effective composition,pinacidil can significantly improve myocardial protection from cardioplegia for immature rabbit hearts.

Myocardial protection during heart surgery in China

Myocardial protection （MP） is the key for cardiopulmonary bypass （CPB） heart surgery. MP during cardiac surgery （CS） aims to preserve myocardial function while providing a bloodless and motionless operating field. Strategies on how to attenuate or prevent post-ischemic myocardial dysfunction that occurs intra-operatively during CS have been discussed for more than half a century. In 1950, Bigelow et al, first reported to decrease myocardial oxygen demand by means of hypothermia. Moreover, Melrose and coworkers2 described the use of electromechanical cardiac arrest induced by potassium infusion, permitting CS to be performed on a non-beating flaccid heart and clear surgical field. The combination of both of these techniques has been the golden standard in MP during surgery until now, allowing surgery with excellent clinical outcome. In 1975, Braimbridge et al introduced a crystalloid solution into clinical practice at St. Thomas Hospital. By the 1980s, blood-based potassium solutions were advocated to further improve MP and to reduce myocardial enzymes release based on the theory that blood would be a superior delivery vehicle for its oxygenating and buffering capacity.Fortunately, the majority of MP strategies now available do allow patients to undergo conventional and complex CS with an operative mortality rate ranging from less than 2% to 4%.

MORPHOMETRIC EVALUATION ON MYOCARDIAL PROTECTION OF COLD CRYSTALLOID VERSUS WARM BLOOD CARDIOPLEGIA

Twenty patients undergoing open-heart valve replacement were divided randomly into two groups in this study; intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) (hypothermic group) and continuous administration of warm blood cardioplegia with normothermic CPB (normothermic group) respectively. Tissue samples were taken from the right atrium before weaning from CPB and from the right appendage 30 minutes after removal of the cross-clamp. The results of pathological study in these two groups were as follows: the structural alterations were most severe during the ischemic period in the hypothermic group. Damages of the myocardial

Blocking the Aryl Hydrocarbon Receptor Alleviates Myocardial Ischemia/Reperfusion Injury in Rats

Objective Restoring the blood perfusion of ischemic heart tissues is the main treatment for myocardial ischemia.However,the accompanying myocardial ischemia reperfusion injury(IRI)would aggravate myocardial damage.Previous studies have confirmed that aryl hydrocarbon receptor(AhR)is closely correlated to kidney and intestinal IRI.The present study aimed to explore the relationship between AhR and myocardial IRI.Methods An oxygen glucose deprivation/reoxygenation(OGD/R)model of H9c2 cells and an ischemia/reperfusion(I/R)model of Sprague-Dawley rat myocardium were established.OGD/R cells and myocardial IRI rats were treated with different concentrations of the AhR antagonist CH-223191 or agonist 6-formylindolo[3,2-b]carbazole(FICZ).Under the conditions of normoxia and hypoxia/reoxygenation,the activity of cardiomyocytes,lactate dehydrogenase(LDH)and cell reactive oxygen species(ROS)were detected.In rats,myocardial pathological damage and markers of myocardial injury were detected.Results According to the results of the cell viability,LDH and ROS tests in vitro,both CH-223191 and FICZ showed no myocardial protection under OGD/R conditions.However,the histological staining and analysis of myocardial injury marker LDH in vitro revealed that CH-223191 could significantly reduce the myocardial IRI.Conclusion AhR exhibited a different effect on myocardial IRI in vitro and in vivo.In vivo,CH-223191 could significantly alleviate the myocardial IRI,suggesting that inhibition of AhR may play a role in myocardial protection,and AhR may serve as a potential treatment target for myocardial IRI.

Effect of Amino Acid Cardioplegia on Myocardial Metabolism and Function of Ischemic Canine Heart

To evaluate the effect of amino acid cardioplegia on myocardial metabolism and function of ischemic canine heart, canine cardiopulmonary bypass (CPB) model was established and the dog heart was subjected to a 120 min ischemic arrest. Animals were divided into 3 groups, group 1:warm blood cardioplegia induction and terminal perfusion plus 4 C ST. Thomas hospital solution (STS)during ischemia;group 2: warm blood cardioplegia enriched with amino acid (L-asparte and L-glutamate 13 mmol/L each) and STS without amino acid (A.G.) and group 3:both warm blood cardioplegic solution and STS enriched with A. G..The result demonstrated that the cardiac function of animals in group 2 and 3 had a significantly better recovery after ischemic-re-perfusion. By the end of ischemia the content of myocardial ATP in group 3 was distinctly higher than that in group 1(P<0. 05), with the release of cardiac enzyme being the least. Myocardial ultra-structure almost remained intact before and after ischemia. Our experiment suggests that the cardioplegia arrest with warm blood and cold crystalloid solution enriched with amino acids could diminish the ischemia-re-perfusion injuries of the heart and enhance the effect of myocardial protection.

The study of myocardial protective effect of creatine phosphate sodium in liver transplant patients

Objective:To study the cardioprotective effectof creatine phosphate sodium by measuring perioperative myocardial enzymes of allogeneic liver transplant patients.Methods:The 26 cases of orthotopic liver transplant patients were randomly divided into control group and creatine phosphate sodium group,13 cases in each group.The creatine phosphate sodium group were given creatine phosphate sodium 30 mg/kg at the time of induction.The control group were given equal amount of N.S.All patients at six-phase of before surgery,after anesthesia,before anhepatic phase,anhepatic phase,new liver and the 12 hours after surgery extraction radial artery.The CK,CK-MB and cTnI activity was measured.Results:To compared with control group,creatine phosphate sodium group’s plasma CK,CK-MB and cTnI concentrations in before anhepatic phase,anhepatic phase,new liver and the 12 hours after surgery 4 phase are significantly lower(p<0.05).Conclusions:The creatine phosphate sodium has a protective effect on liver transplantation in patients with myocardial damage.

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 mitral valve replacement （MVR） with cardiopulmonary bypass （CPB）. Metheds： Forty patients undergoing selective MVR were randomly assigned to the control group and trial Groups Ⅰ, Ⅱ,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. Cenclusiens： 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.

Myocardial protection with pinacidil induced hyperpolarized arrest during cardiopulmonary bypass

Objective To investigate the myocardial protective effects of pinacidil induced hyperpolarized arrest and compare with those afforded by conventional depolarized hyperkalemic arrestMethods Eighteen dogs were equally divided into three groups: normothermic hyperpolarized group (Group A), hypothermic hyperpolarized group (Group B), and hyperkalemic group (Group C) Pinacidil (50μmol/L) containing 37℃ St Thomas solution (K+5mmol/L, 10ml/kg), pinacidil (50μmol/L, Sigma, USA) containing 4℃ St Thomas solution (K+ 5mmol/L, 10ml/kg) and 4℃ standard St Thomas solution (K+ 16mmol/L, 10ml/kg) were infused respectively through the aortic root after aorticclamping Heart arrest and its recovery, ultrastructure of the myocardium, the level of serum myocardial enzymes, and lipid peroxide and adenine cleotide of the myocardium were measuredHemodynamics during ischemia and after reperfusion were observedResults The percentages of normal mitochondria and glycogen did not change much during ischemia (except at 60 min) and after reperfusion in B Group, but declined markedly in Group C 30 min and 60 min after ischemia and 20 min after reperfusion (P<0.01) In Group A,they were lower than those of Group B before ischemia, but higher than those of Group C The recoveries of CO, SV, CI, LVSW, RVSW and MAP in Group B were significantly better than those in other two groups 15 min and 30 min after reperfusion (P<0.05and0.01, respectively) However, they were still better in Group A than those in Group C(P<0.05 and 0.01, respectively)The onset of heart arrest was faster in Groups C and B than that in Group A Highly elevated serum myocardial enzymes were observed 60 min after ischemia and 20 min after reperfusion in Group C, while they were only mild in the hyperpolarized groups, especially in Group B, and their recoveries were rapid Adenine nucleotides of the myocardium were better preserved in Group B than in other two groups 30 min, 60 min after ischemia, and 20 min after reperfusion (P<0.05 and 0.01, respectively)They were also much better in Group A than in GroupC(P<0.05and0.01,respectively)Lipid peroxide of the myocardium were significantly lower in Group B than in other groups 20 min after reperfusion (P<0.01),and they were lower in Group A than in Group C(P<0.05) Conclusions Myocardial protection for global ischemia during cardiopulmonary bypass (CPB) could be achieved with hyperpolarized heart arrest induced by pinacidil, an ATP sensitive potassium channel opener,especially in the hypothermic state The protection is weaker in normothermia but is still superior to that with traditional depolarized hyperkalemic arrest

Effect of ecdysterone on heteroptopic heart transplantation in rats

Objective： To investigate the protective effects of ecdysterone（EDS） on the allograft heart transplant model of rats. Methods： Fifty healthy Sprayue-Dawley（SD） rats were divided into donors and recipients randomly. Hearts were harvested and placed heterotopically into allogenic recipients. All animals were divided into three groups： sham-operation group（only opening and closing the abdomen, n=l 0）, EDS group（injected intraperitoneally with 20 mg/（kg · day） of EDS, n = 10）, and control group （injected intraperitoneally with normal saline, n = 10）. The pathological changes of myocardial tissue were analyzed by light microscopy and transmission electron microscopy and the levels of myocardial enzymes（GOT, LDH, CPK）, SOD, ET-1, NO, MDA in serum were measured. Tissue samples underwent the detection ofapoptotic cell death by in situ terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling for apoptotic index（M） and also by immunohistochemistry method to study the expressions of Bcl-2 and Bax. Results： Pathological examination and transmission electron microscope observation showed greater myocardium damage in the control group. EDS group showed a decrease in the amount of myocardial enzymes, MDA, ET-1 and an increase in the levels of SOD, NO, compared to the control group. The A1 of EDS group became lower than that of control group, meanwhile the EDS group increased the expression of Bcl-2 and decreased the expression of Bax. Conclusion： EDS has protective effects on heteroptopic heart transplantation, which provides a new idea for myocardial protection in heart transplantation. However, the mechanism of its protective effect needs further research.

Protective Effects of Hyperpolarizing Cardioplegia with Pinacidil on Myocardium in Rats

Whether the ATP sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H K solution containing pinacidil (50 μmol/L) (P1 and P2) and depolarized arrest St. Thomas' solution (S1 and S2) subjected to 15 ℃ hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest. Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.

Orthotopic heart transplantation with prolonged donor ischemic time:report of 3 cases and literature review

Heart transplantation has become an effective therapy for patients with end stage heart failure. The preservation of the donor heart is an important factor that affects the results of the operation. We performed 3 cases of orthotopic heart transplantation and obtained some experience in the preservation of the donor heart. Methods： Three male patients with end stage heart failure received the operation in our department successfully. Doppler echocardiography showed left ventrieular end diameter （LVED） of the patients were 91, 87, and 83 mm, and ejection fraction （EF） were 24%, 20%, 12.9%, respectively. Once the declaration of brain death had been made, the median stemotomy was performed with a sternal saw. Haparin at a dose of 300 U/kg of body weight was administered. After at least 2-min heparin circulation, the procurement proceeded. The superior vena cava and the inferior vena cava were nearly completely divided. When the heart was empty, the ascending aorta was cross-clamped and the St. Thomas solution was infused by gravity. The heart was excised by transection of the inferior vena cava, the superior vena cava and all pulmonary veins. After donor heart was removed, it was infused with University of Wisconsin （UW） solution by gravity at a temperature of 4-6℃, then placed in UW solution for storage during transportation. The temperature of solution was maintained at about 4-6℃. The ischemic times of donor heart were 9, 8 and 6 h, respectively. The bicaval anastomotic heart transplantation was adopted. The left atrial anastomoses were constructed using 3.0 polypropylene. The inferior vene cava anastomosis was constructed, the donor and native aorta were cut to an appropriate length. Then the aorta and main pulmonary artery anastomosis were performed respectively. The superior vene cava anastomosis was usually constructed during the rewarming phase. The intraoperative course with a cardiopulmonary bypass of the 3 patients was 96, 44 and 49 min, respectively. Standard triple immunosuppression therapy was commenced in the immediate post-operative period. Results： The operation procedure was smooth and no perioperative death occurred. The follow-up was carried out carefully. The patient＇s condition was fine in 25, 30 and 32 months after operation. The blood pressure was 130/90, 140/95 and 120/80 mmHg, respectively, and LVED was 51, 49 and 53 mm; EF was 50%, 54% and 60%, respectively. Cardiothoracic ratio was 0.63, 0.55, and 0.64, respectively. Conclusion： Preservation time of donor heart with St. Thomas solution infusion and UW solution storage at 0-4℃ may exceed 6 h, and receive comparable middle-term outcomes.

THE ACTION OF CAPTOPRIL ON SCAVENGING OXYGEN FREE RADICALS

The protective effect of captopril on ischemic myocardium was studied in 40 patients with congenital heart disease accompanied with pulmonary hypertention.Twenty of these patients received captopril 50 mg b.i.d.for three months preoperatively (Group A).The other 20 patients without pretreatment with captopril were used as controls (Group B).In Group A,the cardiac output increased and the pulmonary pressure decreased significantly in the first 24 hours postoperatively,indicating a high cardiac output with a low vascular resistance.The differences or CPK,CPKMB,LDH release between Group A and Group B were highly significant or siguificant from the end of operation to 24 hours postoperatively. Myocardial protection in the reduction of the release of CPK, CPK-MB, LDH might be attributed to action on scavenging oxygen free radicals.

Progresses in the research of Danhong Injection against the cardial ischemia-referfusion injury

Researches in the field of the myocardial ischemia-reperfusion injury are attracting the attentions of clinicians for the treatments that protect cardiac muscle cells from being injured can not only help the patients get recovery but also keep them in health. By clearing the free radicals and reducing calcium overload of myocardial cell, treatments with Danhong Injection will help myocardial cells survive from inflammatory reactions which are triggered by ischemia reperfusion so as that endothelial function will be improved and myocardial cell apoptosis will be inhibited. In all, Danhong Injection is an ideal medicine for protecting myocardial cell against ischemia reperfusion injury.

Comparative analysis of structural characteristics and cardiomyocyte protective effects of glucomannan extracted from Bletilla striata using varied methods

Doxorubicin(DOX)is a widely employed tumor therapy,yet its substantial toxic side effects pose a considerable challenge.Bletilla striata has demonstrated efficacy in preventing and treating these toxic side effects in clinical practice,with polysaccharides identified as the principal active component.In the present study,16 fractions of B.striata polysaccharides(BsPs)were extracted using diverse methods,including hot-water extraction(HWE),ultrasonic-assisted extraction(UAE),enzyme-assisted extraction(EAE),dilute acid-water extraction(ACWE),and dilute alkali-water extraction(ALWE).These extractions were subsequently precipitated at final ethanol concentrations of 80%and 95%,respectively.The investigation encompassed yields,total carbohydrate content(TCC),total protein content(TPC),preliminary structural properties,and anti-DOX myocardial cytotoxic activity.Results indicated that the extraction method significantly influenced the physicochemical properties,associated functional properties,and anti-DOX myocardial cytotoxic activity of BsPs.HWE and UAE yielded higher BsPs quantities.The relative molecular weight(RMW)distribution of BsPs differed notably between HWE or UAE,EAE,ACWE,and ALWE.The RMW of primary BsPs obtained from HWE and UAE(1.9×10^(7)-1.7×10^(7) Da)exceeded that from EAE(7.5×10^(3)-2.8×10^(4) Da)and ALWE(5.1×10^(4)-1.7×10^(4) Da),with smaller molecular weights primarily precipitated by higher ethanol concentrations.BsPs were composed of Man and Glu,with partial fractions containing small amounts of Gal or Ara,displaying varying molar ratios.Notably,BsPs from ACWE exhibited the most significant structural differences,lacking 1,4-α-D-Glcp and a triple-helical structure.Furthermore,BsPs obtained from HWE,UAE,and EAE demonstrated heightened anti-DOX myocardial cytotoxic activity compared to other methods.This study underscored the influence of extraction methods on BsPs’structure and myocardial protective activity,offering a foundation for exploring structural diversity and employing specific extraction methods to extract polysaccharides with robust myocardial protective properties efficiently.

Mechanism of the protective effects of noninvasive limbs preconditioning on myocardial ischemia-reperfusion injury

Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning （IPC）.Methods Forty Wistar rats were randomly divided into four experimental groups. In Group I , the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-,, we administered L-nitro-arginine methyl ester （L-NAME） 10 mg/kg or hexamethonium chloride 20 mg,/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyhetrazolium chloride staining.Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment （ P〉0. 05 ）. The myocardial infarct size （IS） was decreased significantly in Group PL and Group PL-U compared with Group I , and the IS/AAR was 34. 5%± 7.6%, 35.9%±8.6% and58.5%±8.5%, respectively （P〈0.05）. The IS/AAR was 49.1%±6.5% in Group PEN, and there was no significant difference compared with Group I （P〉0. 05 ）.Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.