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Meglumine Adenosine Cyclophosphate for Chronic Heart Failure: A Systematic Review

Objective　To assess the effectiveness and safety of meglumine adenosine cyclophosphate (MAC) for chronic heart failure. Methods　The databases such as Cochrane Central Register of Controlled Trials (Issue 3, 2011), MEDLINE (1950 to March 2011), EMbase (1980 to March 2011), CNKI (1995 to March 2011), and VIP (1989 to March 2011) were searched, and the relevant journals and conference proceedings were also manually retrieved. Then the studies were screened according to predefined inclusion and exclusion criteria, and their quality was evaluated. Meta-analyses were performed by using RevMan 5.0 software. Results　Seventeen randomized controlled trials (RCTs) involving 1 281 patients were included. All of the included RCTs were Grade C in methodological quality. The results of meta-analyses showed that MAC plus routine treatment was superior to routine treatment in improving the left ventricular ejection fraction (WMD=5.75, 95%CI 3.61 to 7.89), stroke volume (SV) (WMD=5.55, 95%CI 3.71 to 7.38), E/A (WMD=0.09, 95%CI 0.05 to 0.14) and 6 min walk test (WMD=43.52, 95%CI 21.00 to 66.04). But MAC plus routine treatment was similar to routine treatment in regulating cardiac index (CO) (WMD=0.20, 95%CI –0.31 to 0.71) and heart rate (WMD=0.64, 95%CI –7.49 to 8.77). No significant adverse effects or allergic reactions were reported. Conclusion　The current evidence shows that MAC may improve the left ventricular ejection fraction, stroke volume, E/A and 6 min walk test. Due to a high risk of selection bias and detection bias in the included studies, the evidence is insufficient to determine the effectiveness of MCA. Further large-scale trials are required to define the role of MAC in the treatment of chronic heart failure.

Effect of Adenosine on Propofol Consumption in Total Intravenous Anesthesia

目的　探讨全凭静脉麻醉中腺苷对丙泊酚用量的影响。 方法　2011年1月－12月期间59例行择期手术的患者全凭静脉麻醉，随机分为腺苷静脉持续输注组（A组）和对照组（B组），A组患者麻醉诱导后持续输注腺苷70 μg/（kg·min），直至术毕。B组麻醉后按常规处理。比较两组患者麻醉时间、苏醒时间、瑞芬太尼用量，麻醉过程中平均动脉压（MAP）、心率，以及麻醉过程中丙泊酚的用量。同时记录使用腺苷过程中的不良反应。 结果　两组患者麻醉时间、苏醒时间、瑞芬太尼用量比较均无明显差异，无统计学意义（P＞0.05）。两组患者麻醉过程中MAP、心率比较亦无明显差异，无统计学意义（P＞0.05）。两组患者麻醉过程中丙泊酚平均用量比较，A组明显低于C组，差异有统计学意义（P＜0.05），且不良反应发生率低。 结论　腺苷能明显降低全凭静脉麻醉中丙泊酚的使用剂量。

ABCA1在胆固醇结石患者胆囊黏膜上皮的表达

An Observation of the Protective Effects of SAdenosylLMethionine on Liver Function in Cirrhotic Rats after Hepatectomy

ObjectiveTo investigate the protective effect of SadenosylLmethionine on liver regeneration and liver function in cirrhotic rats after hepatectomy. MethodsCirrhosis was successfully induced by injection of 40% CCl4.Then,partial hepatectomy (about 30%) was performed in all rats. Cirrhotic rats were divided into 3 groups,namely,cirrhotic group (normal saline 5 ml/d,for 15 postoperative days，n=20),treatment group 1 〔S adenosylLmethionine 10 mg/(kg·d),for 15 postoperative days,n=16〕 and treatment group 2 〔SadenosylL methionine 20 mg/(kg·d),15 postoperative days,n=16〕,and normal control group was also established. Animals were sacrificed at the 15th postoperative day and 30th postoperative day to take samples for detection of liver function (Alb,ALT,TB,TBA) and serum TNFα.Liver tissues were also observed under light microscope and electron microscope. ResultsIn two treatment groups,at the time point (15 postoperative days or 30 postoperative days),concentrations of ALT,TB,TBA,Alb and TNFα were decreased significantly as compared with cirrhotic group (P ＜0.01),and concentration of Alb was increased significantly (P＜0.01).In contrast, there were no obvious difference in the same time point of different dosetreatment groups (Pgt;0.05),but the decrease of ALT,TB,TBA,TNFα and the increase of Alb were more significant at the second time point (30th postoperative day) than the first time point (15th postoperative day) when treated with same dose (P＜0.01).At the same time,concentration between TNF α and ALT,TB,TBA showed a positive correlation (P＜0.01),and the concentration between TNFα and Alb showed a negative correlation (P＜0.01).In addition, the histopathology showed SadenosylLmethionine had effects of protecting liver function and enhancing liver regeneration. ConclusionThe study suggests that SadenosylL methionine has the efficacy of enhancing liver regeneration and improving liver function.

THE ROLE OF NITRIC OXIDE, TXA2/PGI2 AND ATP ON HEPATIC ISCHEMIA/REPERFUSION INJURY IN CIRRHOTIC RATS

The aim of this study is to assess ischemia/reperfusion injury in carbon tetrachloride induced cirrhotic liver as compared to normal liver in the rats. Results showed that in cirrhotic liver, instead of diminishing the hepatic vein nitric oxide level increased significantly after ischemia from 8.04 μmol/L to 11.52 μmol/L and remained high till 5 hrs after reperfusion. The hepatic adenosine triphosphate (ATP) contents decreased as that seen in normal rat but did not restore to normal till the end of 5 hrs after reperfusion. Based on these findings, it is postulated that in cirrhotic liver, ischemia/reperfusion injury is aggrvated as evidenced by of nitric oxide, and extended diminishing in ATP.

STUDY ON THE CHANGES OF cAMP AND cGMP WITHIN PLATELET AND IN SERUM IN THE COURSE OF CANINE INFERIOR VENA CAVA RECONSTRUCTION

The Dacron grafts seeded with autologous venous fragments were implanted into IVC of 13 canines as seeded group and the control grafts (8 cases), which were only preclotted with fresh blood. The amounts of cAMP and cGMP in serum and within platelet were measured. All of the specimens explanted at exsaguination were observed morphologically. The results shown that the total patency rate were 61.5% in seeded group, but 25.0% in control one and new endothelial lining formed at two weeks after implantation of the seeded grafts. The amounts of cAMP in serum and within platelet were higher in seeded group, but the amounts of cGMP were lower in serum and within platelet. These were in accordance with the results that the endothelialization of the grafts were complete in seeded group but not complete in control one. The results indicate that seeding Dacron with autologous venous fragment makes new endothelium formed at two weeks after implantation, increases the amounts of cAMP in serum and within platelet, but reduces the amounts of cGMP and thus improves graft patency rate.

Evaluation of Adenosine Monophosphate Bronchoprovocation Test in Asthmatics

Objective To evaluate the clinical value and safety of adenosine monophosphate( AMP)bronchoprovocation test in patients with asthma. Methods Sixty asthmatics, including 19 cases with uncontrolled asthma, 22 with partially controlled asthma, and 19 with controlled asthma were enrolled. Twenty-four healthy volunteers were enrolled as control and 20 patients with upper respiratory tract infection ( URI) were also included. AMP bronchoprovocation test ( AMP-BPT) was performed. PD20 FEV1-AMP lt;40 mg was set as a cut-off value of positive response to AMP. Positive rate, sensitivity, specificity, accuracy and adverse reactions of AMP-BPT were evaluated. Eleven cases with uncontrolled asthma and 12 cases with partially controlled asthma were followed up with AMP-BPT three months and six months after inhaledcorticosteroids treatment. Asthma symptom scores were recorded a week early before each challenge. The correlation between PD20FEV1 -AMP and asthma symptom score was analyzed. Values of PD20 FEV1 -AMP were represented as median and quartile range [ M( QR) ] . Results No positive responses to AMP were found in both healthy and URI subjects. On the other hand, positive responses to AMP were found in all the uncontrolled asthmatics ( 100% ) with PD20FEV1 -AMP as 0. 6 mg ( 0. 4 mg) , in 19 partially controlled asthmatics ( 86. 4% ) with PD20 FEV1 -AMP as 5. 38 mg ( 32. 67 mg ) , and in 5 controlled asthmatics( 26. 3% ) with PD20FEV1 -AMP as 40 mg ( 29. 3 mg) . There were negative correlations between the logarithms of PD20 FEV1 -AMP and logarithms of asthma symptom scores ( r = - 0. 598, P lt; 0. 01) . The sensitivity, specificity and accuracy was 72% , 100%, and 84% , respectively. Percentage of subjects who experienced wheezing, cough, dyspnea, swallows stimulation, chest tightness, expectoration and cyanosis during AMP-BPT were 37. 5%, 21. 2%, 15. 4%,7. 7%, 7. 7%, 4. 8%, and 1. 0%, respectively. No severe adverse reaction was found. Conclusions AMP-BPT is helpful to the diagnosis and differential diagnosis of bronchial asthma. It also can be used to evaluate the severity and control level, and to monitor the therapeutic efficacy in clinical practice. Moreover, AMP-BPT is well tolerated with little adverse reaction.

Effects of Adiponectin on Proliferation of Airway Smooth Muscle Cells and Activation of Adenosine Monophosphate-Activated Protein Kinase

Objective To investigate the effect of adiponectin on proliferation of airway smooth muscle cells( ASMCs) , and explore its possible mechanism. Methods ASMCs were derived fromrat airway tissue and were cultured in vitro. RT-PCR was used to verify the expression of adiponectin receptors on ASMCs. Then ASMCs were treated with adiponectin at different concentrations( 5, 10, 20, 40, 80 μg/mL) for different periods of time( 1, 12, 24, 48, 72 hours) , respectively. The absorbsence ratios of adiponectin at different concentrations were determined by MTT assay. The adenosine monophosphate-activated protein kinase( AMPK) and phosphorylated AMPK( pho-AMPK) in ASMCs were quantified by Western blot after being treated with adiponectin at different concentrations ( 5, 10, 20, 40 μg/mL) for 48 hours. ResultsThe inhibition of adiponectin on ASMCs was showed in dose-dependent manner( r = 0. 324, P lt; 0. 01) and time-dependent manner( r = 0. 607, P lt; 0. 05) . Western blot indicated that the expression of pho-AMPK increased with the increased concentrations of adiponectin( r =0. 607, P lt; 0. 01) . The ratio of pho-AMPK/AMPK were ( 27. 66 ±1. 03) % , ( 31. 91 ±0. 86 ) %, ( 75. 52 ±2. 67) % , and ( 84. 50 ±1. 05) % ,respectively, with significant differences between each concentrations of adiponectin( P lt; 0. 05) . There was no expression of pho-AMPK in the control group. Conclusion Adiponectin can significantly inhibit ASMCs’proliferation by activating AMPK.

腺苷含血心脏停搏液在心瓣膜置换术中对心肌的保护作用

摘要: 目的 研究含血心脏停搏液中加入外源性腺苷在心瓣膜置换术中对心肌的保护作用。 方法 将32例行心瓣膜置换术患者随机分为两组，腺苷组在含血心脏停搏液中加入外源性腺苷，对照组单用含血心脏停搏液，分别经主动脉根部或切开主动脉经冠状动脉窦直接灌注。于术前、主动脉开放后6 h、24 h、72 h采集患者桡动脉血，监测心肌肌酸激酶同工酶(CKMB)、肌钙蛋白I(cTnI)；观察心脏停搏情况，术后机械辅助通气时间及术后正性肌力药物的应用情况；透射电子显微镜观察心肌超微结构的改变。 结果 两组患者均无死亡。腺苷组诱导心脏停搏时间较对照组短(P=0.021)；腺苷组的CK-MB水平在主动脉开放后6 h、24 h，cTnI水平在主动脉开放后6 h、24 h、72 h均较对照组低(Plt;0.05);两组机械辅助通气时间和术后多巴胺使用剂量差异无统计学意义(Pgt;0.05)；腺苷组心肌超微结构心肌损伤较对照组明显减轻。 结论 外源性腺苷加入心脏停搏液中能显著提高对心肌的保护效果。

Role of Cyclic Adenosine Monophosphate Signaling Pathway in Myocardial Protection by Diazoxide Preconditioning: Experiment with Isolated Rat Hearts

Abstract： Objective To study the changes of the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) expression of isolated rat hearts after diazoxide preconditioning (DPC), and to explore the possible mechanism of cAMP signaling pathway in myocardial protection by DPC. Methods Isolated working heart Langendorff perfusion models of 40 Wistar rats were set up and were divided randomly into four groups. For the ischemia reperfusion injury(I/R) group (n=10), 30 min of equilibrium perfusion was followed by a 60 min reperfusion of KrebsHenseleit (K-H) fluid. The DPC group (n=10) had a 10 min equilibrium perfusion and two cycles of 5 min of 100 μmol/L diazoxide perfusion followed by a 5 min diazoxidefree period before the 30 min ischemia and the 60 min reperfusion of K-H fluid. The blank control group (control group, n=10) and the Dimethyl Sulphoxide(DMSO) group (n=10) were perfused with the same treatment as in the DPC group except that diazoxide was replaced by natriichloridum and DMSO respectively. The activity of creatine kinase (CK) in coronary outflow, the activity of malonyldialdehyde (MDA) and superoxide dismutase (SOD) in myocardium were detected. And the scope of myocardial infarction and the concentrations of myocardial cAMP and PKA were also assessed. Results Compared with the I/R group, the level of MDA for the DPC group decreased significantly (8.28±2.04 nmol/mg vs. 15.52±2.18 nmol/mg, q=11.761,Plt;0.05), the level of SOD increased significantly (621.39±86.23 U/mg vs. 477.48±65.20 U/mg, q=5.598,Plt;0.05). After a 30 min reperfusion, compared with the I/R group, the content of CK decreased significantly (82.55±10.08 U/L vs. 101.64±19.24 U/L, q=5.598, Plt;0.05) and the infarct size reduced significantly (5.63%±9.23% vs.17.58%±5.76%, q=6.176,Plt;0.05) in the DPC group. The cAMP concentration in the DPC group was much higher than that in the I/R group (0.64±0.07 pmol/g vs. 0.34±0.05 pmol/g, q=14.738,Plt;0.05), and PKA concentration was also much higher than that in the I/R group ［17.13±1.57 pmol/(L·min·mg) vs. 12.85±2.01 pmol/(L·min·mg), Plt;0.05］. However, there were no significant differences between the I/R group, DMSO group and the control group in the above indexs (Pgt;0.05). Conclusion DPC significantly improves the releasing of cAMP and PKA, decreases oxygen free radicals, and relieves myocardial ischemia reperfusion injury. The cAMP signaling pathway may be involved in triggering the process of myocardial protection mechanisms of DPC.