Appraisal of Guidelines for the Management of Blood Pressure in Patients with Diabetes Mellitus: The Consensuses, Controversies and Gaps

Background@#Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. @*Methods@#Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. @*Results@#In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. @*Conclusion@#The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Appraisal of Guidelines for the Management of Blood Pressure in Patients with Diabetes Mellitus: The Consensuses, Controversies and Gaps

Background@#Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. @*Methods@#Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. @*Results@#In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. @*Conclusion@#The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Nicorandil protects H9 c2 cardiac cells against high glucose-induced injury and inflammation / 中国药理学通报

Aim To investigate whether nicorandil (Nic)protects H9c2 cardiac cells against high glucose (HG)-induced injury and inflammation by inhibiting nuclear factor-κB (NF-κB )/cyclooxygenase-2 (COX-2 )pathway.Methods Cell viability was measured by cell counter kit-8 (CCK-8)assay.The expression lev-els of NF-κB,COX-2 and cleaved caspase-3 were de-termined by Western blot.The activity of lactate dehy-drogenase (LDH)in the culture medium was measured with commercial kits.The intracellular level of reactive oxygen species (ROS)was detected by 2′,7′-dichlor-fluorescein-diacetate (DCFH-DA)staining followed by photofluorography.The number of apoptotic cells was observed by Hoechst 33258 nuclear staining followed by photofluorography.Mitochondrial membrane poten-tial (MMP)was examined by rhodamine 123 staining followed by photofluorography.The secretion levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA.Results After H9 c2 cardiac cells were treated with 35 mmol · L-1 glucose (high glucose,HG)for 24 h,the cell viability was significantly decreased .Pre-treatment of the cells with 20~100 μmol·L-1 Nic for 60 min or 50 μmol· L-1 Nic for 30~120 min before exposure to HG signif-icantly attenuated the decrease in viability induced by HG.On the other hand,HG increased the expression levels of phosphorated (p)-NF-κB p65 and cyclooxy-genase-2 (COX-2 )in H9c2 cardiac cells.Pre-treat-ment of the cells with 50 μmol·L-1 Nic for 60 min at-tenuated the up-regulation of p-NF-κB p65 and COX-2 expression levels induced by HG.Furthermore,HG induced considerable injuries and inflammatory re-sponse,leading to increases in LDH activity,ROS generation,MMP loss,the number of apoptotic cells, the expression of cleaved caspase-3 as well as the se-cretion levels of IL-1βand TNF-α.Pre-treatment of the cells with 50 μmol·L-1 Nic for 60 min before HG exposure,or co-treatment of the cells with 100 μmol· L-1 PDTC (an inhibitor of NF-κB)or 10 μmol·L-1 NS-398 (an inhibitor of COX-2)and HG for 24 h ob-viously reduced the above injuries and inflammatory re-sponse induced by HG. Conclusion Nic protects H9 c2 cardiac cells against HG-induced injury and in-flammation by inhibiting NF-κB/COX-2 pathway.

Interaction between necroptosis and p38MAPK pathway mediates high glucose-induced injury in H9 c2 cardiac cells / 中国药理学通报

Aim To investigate the role of the interac-tion between necroptosis ( Nec ) and p38 mitogen-acti-vated protein kinase ( MAPK) pathway in the high glu-cose (HG)-induced H9c2 cardiac cells injury.Meth-ods The cell viability was measured by cell counter kit-8 assay .The intracellular level of reactive oxygen species ( ROS ) was tested by DCFH-DA stating fol-lowed by photofluorography .Mitochondrial membrane potential ( MMP) was detected by Rhodamine 123 stai-ning followed by photofluorography . The expression levels of receptor interaction protein 3 ( RIP3, an indi-cator of Nec ) and p38 MAPK protein were tested by Western blot assay .Results The treatment of H9c2 cardiac cells with 35 mmol? L-1 glucose ( high glu-cose, HG) for 24 h induced considerable injuries , in-cluding a decrease in cell viability , increases in ROS generation as well as MMP loss .The co-treatment of the cells with 100 μmol? L-1 necrostatin-1(Nec-1,a specific inhibitor of Nec ) and HG for 24 h or the pre-treatment of the cells with 3 μmol? L-1 SB 2 0 3 5 8 0 ( an inhibitor of p38MAPK) for 60 min before HG exposure attenuated the above injuries induced by HG .Moreo-ver, the treatment of the cells with HG for 1,3,6,9, 12 ,24 ,36 and 48 h significantly increased the expres-sion levels of RIP3, peaking at 24 h.The co-treatment of the cells with 100 μmol? L-1 Nec-1 or the pre-treatment of the cells with 3 μmol? L-1 SB203580 considerably blocked the up-regulation of RIP3 expres-sion induced by HG .On the other hand , the co-treat-ment of the cells with 100 μmol? L-1 Nec-1 alleviated the HG-induced up-regulation of the expression of p-p38MAPK.Conclusion The interaction between Nec and p38 MAPK pathway mediates the HG-induced inju-ry in H9c2 cardiac cells.

Opening of ATP-sensitive K+channels protects H9c2 cardiac cells against high glucose-induced injury and inflammation by inhibiting TLR4/NF-κB pathway / 中国病理生理杂志

AIM:To investigate whether the opening of ATP-sensitive K+(KATP) channels protects H9c2 car-diac cells against high glucose ( HG)-induced injury and inflammation by inhibiting the Toll-like receptor 4 ( TLR4 )/nu-clear factor-κB ( NF-κB) pathway.METHODS:The protein levels of TLR4 and NF-κB p65 were determined by Western blot.The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA.The cell viabil-ity was measured by CCK-8 assay.Mitochondrial membrane potential (MMP) was examined by rhodamine 123 (Rh 123) staining followed by photofluorography.The intracellular levels of reactive oxygen species ( ROS) were detected by 2′, 7′- dichlorfluorescein-diacetate (DCFH-DA) staining followed by photofluorography.The number of apoptotic cells was ob-served by Hoechst 33258 nuclear staining followed by photofluorography.RESULTS: After the H9c2 cardiac cells were treated with HG (35 mmol/L glucose) for 24 h, the protein levels of TLR4 and phosphorylated NF-κB p65 ( p-NF-κB p65) were significantly increased.Pretreatment of the cells with 100 μmol/L diazoxide ( DZ, a KATP channel opener) for 30 min before exposure to HG considerably blocked the up-regulation of the TLR4 and p-NF-κB protein levels induced by HG.Moreover, co-treatment of the cells with 30 μmol/L TAK-242 (an inhibitor of TLR4) obviously inhibited the HG-in-duced up-regulation of the p-NF-κB p65 protein level.On the other hand, pretreatment of the cells with 100 μmol/L DZ had a clear myocardial protection effect, which attenuated the HG-induced cytotoxicity, inflammatory response, mitochon-drial damage, oxidative stress and apoptosis, evidenced by an increase in the cell viability, and decreases in the levels of IL-1βand TNF-α, MMP loss, ROS generation and the number of apoptotic cells.Similarly, co-treatment of H9c2 cardiac cells with 30μmol/L TAK-242 or 100μmol/L PDTC ( an inhibitor of NF-κB) and HG for 24 h also obviously reduced the above injuries and inflammation induced by HG.CONCLUSION: The opening of KATP channels protects H9c2 cardiac cells against HG-induced injury and inflammation by inhibiting the TLR4/NF-κB pathway.

Hydrogen sulfide protects H9c2 cardiomyocytes against high glucose-in-duced injury by inhibiting necroptosis / 中国病理生理杂志

AIM:To study whether hydrogen sulfide (H2S) protects H9c2 cardiomyocytes against high glucose ( HG)-induced injury by inhibiting necroptosis .METHODS:The protein levels of RIP3 ( an indicator of necroptosis ) and cleaved caspase-3 were determined by Western blot .The cell viability was measured by CCK-8 assay.The intracellular le-vels of reactive oxygen species (ROS) were detected by 2’, 7’-dichlorfluorescein diacetate staining followed by photofluo-rography.Mitochondrial membrane potential (MMP) was examined by rhodamine 123 staining followed by photofluorogra-phy.The number of apoptotic cells was observed by Hoechst 33258 nuclear staining followed by photofluorography .RE-SULTS:After the H9c2 cells were treated with HG (35 mmol/L glucose) for 0~24 h, the protein expression of RIP3 in the H9c2 cells was significantly increased at 3 h, 6 h, 9 h, 12 h and 24 h, reaching the maximum level at 24 h.Pretreat-ment of the cells with 400μmol/L NaHS (a donor of H2S) or co-treatment of the cells with necrostatin-1 (Nec-1;a speci-fic inhibitor of necroptosis) considerably blocked the up-regulation of RIP3 protein induced by HG.Moreover, pretreatment with NaHS or co-treatment with Nec-1 obviously inhibited HG-induced injuries , leading to an increase in the cell viability , and decreases in the generation of ROS and MMP loss .On the other hand , pretreatment with NaHS also reduced the num-ber of apoptotic cells and the protein level of cleaved caspase-3 in the HG-treated H9c2 cardiomyocytes .CONCLUSION:H2 S protects H9c2 cardiomyocytes against HG-induced injury by inhibiting necroptosis .

N-acetylcysteine protects H9c2 cells against injuries induced by methyl-glyoxal / 中国病理生理杂志

AIM:To investigate the protective effect of N-acetylcysteine (NAC) on H9c2 cells from injuries induced by methylglyoxal (MG) and the potential mechanism.METHODS:H9c2 cells were divided into control group, MG treatment group, NAC +MG treatment group, SP600125 pretreatment +MG group, NAC group and SP600125 group.The viability of the H9c2 cells was measured by CCK-8 assay.The protein levels of p-JNK and t-JNK were tested by Western blot .The changes of intracellular reactive oxygen species ( ROS) were evaluated by 2′, 7′-dichlorofluorescein di-acetate (DCFH-DA) staining.Mitochondrial membrane potential (MMP) was measured by rhodamine 123 (Rh123) stai-ning.The morphological changes in apoptotic cardiomyocytes were detected by Hoechst 33258 staining.RESULTS: Du-ring 100~800 μmol/L concentration range , MG caused significantly reduced viability of the H 9c2 cells in a dose-depend-ent manner.NAC had a protective effect on H9c2 cells against the injuries induced by MG during 500~1 500μmol/L con-centration range through raising cell viability , inhibiting cellular oxidative stress and improving MMP ( P <0.01 ) . SP600125,an inhibitor of JNK, showed the protective effect similar to NAC on H9c2 cells against MG-induced injuries, in-cluding attenuating oxidative stress , improving MMP and suppressing apoptosis .CONCLUSION: N-acetylcysteine offers obvious protective effect on H9c2 cells against the injuries induced by methylglyoxal .The underlying mechanisms may be associated with decreasing the production of ROS , ameliorating MMP , inhibiting the activation of JNK and suppressing ap-optosis.

Role of ATP-sensitive potassium channels-Akt pathway in hydrogen sulfide inhibiting high glucose-induced injury in H9 c2 cardiac cells / 中国药理学通报

Aim To investigate the role of ATP-sensi-tive potassium channels-Akt pathway in exogenous hy-drogen sulfide( H2 S) inhibiting the high glucose( HG)-induced injury in H9c2 cardiac cells. Methods The expression level of Akt protein was tested by Western blot assay. The cell viability was measured by cell counter kit-8(CCK-8 assay). The number of apoptotic cells was tested by Hoechst 33258 nuclear staining fol-lowed by photofluorography. The intracellular levels of reactive oxygen species ( ROS ) were detected by DCFH-DA staining followed by photofluorography. Mi-tochondrial membrane potential ( MMP ) was examined by JC-1 staining followed by photofluorography. Results H9c2 cells were treated with 35 mmol·L-1 glucose (high glucose, HG) for 0 ~24 h respectively. After treating for 3 h, the expression level of phosphorated ( p )-Akt protein began to be obviously reduced, the maximum reduced expression level was observed after the cells were exposed to HG for 24 h. Pretreatment of the cells with 50 μmol · L-1 pinacidil ( Pin, a KATP channel opener) or 400 μmol·L-1 NaHS( a donor of H2 S) prior to exposure to HG considerably blocked the down regulation of p-Akt expression level induced by HG. However, pretreatment with 1 mmol · L-1 KATP channel blocker glibenclamide( Gli) obviously attenua-ted the inhibitory effect of NaHS on HG-induced down-regulation of p-Akt expression level. On the other hand, the protective effects of NaHS against the HG-induced cardiomyocyte injury were markedly blocked by 30 μmol·L-1 Ly294002(an inhibitor of Akt), as indicated by the decrease in cell viability and MMP dissipation as well as the increases in the number of apoptotic cells and ROS generation. Conclution KATP channels-Akt pathway mediates the protective effect of H2 S against the HG-induced cardiac injury.

Role of ATP-sensitive potassium channels in inhibitory effect of hydrogen sulfide on high glucose-induced injury in H9c2 cardiac cells / 中国病理生理杂志

AIM:To investigate the roles of ATP-sensitive potassium ( KATP ) channels in high glucose-induced cardiac injury and the inhibitory effect of hydrogen sulfide ( H2 S) on the cardiomyocyte injury.METHODS:The expres-sion level of KATP channel protein was tested by Western blot.The cell viability was measured by CCK-8 assay.The number of apoptotic cells was observed by Hoechst 33258 nuclear staining.Mitochondrial membrane potential ( MMP) was exam-ined by JC-1 staining.RESULTS:After the H9c2 cells were treated with 35 mmol/L glucose ( high glucose, HG) for 1~24 h, the protein level of KATP channel was significantly reduced at 6 h, 9 h, 12 h and 24 h, reaching the minimum level at 12 h and 24 h.Pretreatment of the cells with 400μmol/L NaHS ( a donor of H2 S) prior to exposure to HG for 12 h con-siderably blocked the down-regulation of KATP channels induced by HG.Pretreatment of the cells with 100 μmol/L mito-chondrial KATP channel opener diazoxide, 50μmol/L non-selective KATP channel opener pinacidil or NaHS obviously inhibi-ted HG-induced injuries, leading to an increase in the cell viability, and decreases in the number of apoptotic cells and the MMP loss.Pretreatment with 100μmol/L mitochondrial KATP channel antagonist 5-hydroxydecanoic acid or 1 mmol/L non-selective KATP channel antagonist glibenclamide attenuated the above cardioprotective effects of NaHS.CONCLUSION:KATP channels mediate the inhibitory effect of H2 S on HG-induced cardiac injury.

Edaravone protects H9 c2 cells against doxorubicin-induced cardiotoxicity / 中国药理学通报

Aim To explore whether edaravone (EDA), a novel free radical scavenger, protects H9c2 cardiac cells against doxorubicin ( DOX )-induced car-diotoxicity. Methods H9c2 cells were treated with 5μmol·L-1 DOX to establish a model of DOX cardio-toxicity. Cell viability was examined by cell counter kit ( CCK-8 ) . Changes in morphology and amount of ap-optotic cells were detected by Hoechst 33258 staining;intracellular level of reactive oxygen species ( ROS ) was measured by DCFH-DA staining and photofluorog-raphy;mitochondrial membrane potential ( MMP) was observed by rhodamine 123 ( RH123 ) staining and photoflurograph; the expression level of caspase-3 was determined by Western blot assay. Results Pretreat-ment of H9 c2 cells with 20 , 40 and 80 μmol · L-1 EDA for 60 min markedly inhibited cytotoxicity in-duced by 5 μmol · L-1 DOX, respectively, as evi-denced by an increase in cell viability. The protective effect induced by 40 μmol · L-1 EDA was maximal. Pretreatment of H9 c2 cells with 40 μmol · L-1 EDA for 30 , 60 , 90 and 120 min significantly attenuated DOX-induced cytotoxicity, respectively, having a max-imal protection at 60 min. Furthermore, pretreatment of H9 c2 cells with 40 μmol · L-1 EDA for 60 min be-fore exposure to 5 μmol · L-1 DOX for 24 h obviously reduced cardiac injuries, as evidenced by decreases in the DOX-induced intracellular ROS generation, num-ber of apoptotic cells, and expression of cleaved caspase-3, as well as loss of MMP. Conclusions EDA can protect H9 c2 cardiac cells against DOX-in-duced cardiotoxicity, this protection may be associated with inhibition of ROS production and preservation of MMP.

Effects of Hirudin on Ventricular Arrhythmia after Acute Myocardial Infarction in Rats / 中山大学学报(医学科学版)

[Objective] To determine the effects and possible mechanism of the thrombin antagonist r-RGD-Hirudin (HIR) on ventricular arrhythmia(VA) after acute myocardial infarction (AMI). [Methods] Seventy adult male Sprague-Dawley rats were randomly subjected to the 10 groups according to duration of left coronary occlusion: HIR 0 min, HIR 5 rain, HIR 10 min, HIR 20 min, HIR 30 min, and normal saline(NS) 0 min, NS 5 min, NS 10 min, NS 20 min, NS 30 min; and the average of every group is 7 rats. Acute myocardial infarction was produced by the occlusion of the left anterior descending coronary artery, then the measurements of arrhythmia and infarction sizing by Evans blue were assessed as well as the expression of three isoforms of inositol 1,4,5-trisphosphate receptors (IP3Rs) mRNA in isehemic myocardium by reverse transeriptase polymerase chain reactions (RT-PCR). [Results] Compared with NS groups, the measurements of VA in HIR were reduced significantly in 5 to 20 minutes after AMI (P<0.05). The incidence of VA was all positive related to the expression of three isoforms of IP3Rs mRNA (P<0.01). Compared with NS groups, the expression of type2,inositol 1,4,5-trisphosphate receptor (IP3R2) mRNA at 10 min and type3, inositol 1,4,5-trisphosphate receptor mRNA (IP3R3) at 10 min and 20 min after AMI were significant decreased (P<0.05) in HIR groups. [Conclusion] The thrombin antagonist r-RGD-Hirudin exerts its myocardial protection against ventricular arrhythmia after acute myocardial infarction possible through IP3R2 and IP3R3 and not typel, inositol 1,4,5-trisphosphate receptor (IP3R1).

Roles of heat shock protein 90 in the blockage of H2S against cardiomyocyte injuries induced by chemical hypoxia / 中国病理生理杂志

AIM: To explore the roles of heat shock protein 90 (HSP90) in the blockage of hydrogen sulfide (H2S) against chemical hypoxia-mimetic agent (cobalt chloride, CoCl_2)-induced oxidative stress injuries in H9c2 cardiac cell. METHODS: H9c2 cells were treated with CoCl_2 to set up the chemical hypoxia-induced the model of cardiomyocyte injury. Sodium hydrosulfide (NaHS, a H2S donor) was added into medium for 30 min before CoCl_2 treatment. ATP content was detected by high performance liquid chromatogram (HPLC). Mitochondrial membrane potential (MMP) was measured by rhodamine123 (Rh123) staining and photofluorography. The activity of superoxide dismutase (SOD) was observed using a SOD kit. The expression of heme oxygenase-1 (HO-1) was evaluated by Western blotting. RESULTS: CoCl_2 at concentration of 600 μmol/L significantly reduced SOD activity, ATP level and MMP, and enhanced the expression of HO-1 in H9c2 cells. Pretreatment with 400 μmol/L NaHS dramatically inhibited the cytotoxicity induced by CoCl_2, increased SOD activity, ATP level and MMP, decreased HO-1 expression. 17-allylamino-17 demethoxygeldanamycine(17AAG), an inhibitor of HSP90, obviously blocked the inhibitory effect of H2S on the CoCl_2-induced cytotoxicity, reduced the levels of ATP and MMP, increased HO-1 expression. However, no significantly influence on SOD activity was observed. CONCLUSION: HSP90 may mediate the cardioprotection of H2S via inhibiting the oxidative stress induced by chemical hypoxia.

The clinical significance of soluble thrombomodulin in acute coronary syndrome / 中国医师进修杂志

Objective To study the levels of soluble thrombomodulin (sTM)in patients with acute coronary syndrome (ACS) and evaluate its clinical significance. Method Measured the sTM levels with enzyme linked immunosorbent assay, and described the characteristics of coronary arteriography, risk factors of coronary heart disease, and adverse events in a case-control study of 48 ACS patients (ACS group)and 10 normal people (control group). Results The level of sTM in ACS group was (3.67±1.71) μg/L, and (2.34±0.43)μg/L in control group (P<0.05). The level of sTM in the patients of risk factors or impaired vessels number more than 2 increased significantly than those in the patients of risk factors or impaired vessols number inferior or equal to 2, (4.93±2.76) μg/Lvs (3.13±0.81) μg/L, P<0.05, (4.60± 2.83) μg/L vs (2.91±0.23) μg/L, P < 0.05 respectively. The incidence of cardiac events in the patients of sTM more than 3.2 μg/L (70.0%)was higher significantly than that in the patients of sTM inferior or equal to 3.2 μg/L(35.7%), P< 0.05. Conclusions The levels of sTM are valuable markers to evaluate the impaired degree and scope of endothelial cells in ACS. They are also associated with the number of risk factors, and useful in predicting the extent and prognosis of the disease.

Effects of TIMI risk index on predicting prognosis m patients with ST-elevation myocardial infarction / 中华急诊医学杂志

Objective To evaluate the value of the TIMI risk index in predicting 30-day and one-yosr mortality and incidence of heart failure in patients with ST-elevation myocardial infarction (STEMI).Method Data of 229 patients with STEM1 from August 1999 to March 2006 in the First Affiliated Hospital,Sun Yat-sen University,were retrospeclively collected,analyzed and scored with TIMI risk index.When categorized into quintiles(≤12.5,12.5～17.5,17.5～22.5,22.5～30,>30) and modeled as a continuous variable,difference of prediction of 30day and one-year mortality and 30-day incidence of heart failure of patients were compared respectively.Results When categorized into quintilos and modeled as a continuous variable,30-day and one-year mortality and 30-day incidence of heart failure were increasing with increasing score of risk index (P<0.05).The area under the recewer operating characteristic curve were 0.65,0.68,0.67 and 0.70,0.72,0.70,respectively.Conclusions The TIM1 risk index can be used as a simple,rapid and practical tool to risk-stratify patients with STEMI.

In vivo adaptive response of the peripheral conduit artery in patients with borderline systolic hypertension / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate elastic changes of the radial artery, a medium-sized muscular peripheral conduit artery, in patients with borderline systolic hypertension.</p><p><b>METHODS</b>Using a non-invasive high-resolution echo-tracking device coupled to a photoplethysmography (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured radial artery elastic parameters of 20 patients with borderline systolic hypertension and 20 normal subjects according to Langewouters model.</p><p><b>RESULTS</b>The diameter of the radial artery of control subjects and those with borderline systolic hypertension at the isobaric level of 100 mmHg and mean arterial pressure was similar, but the compliance and distensibility at similar conditions in patients with borderline systolic hypertension did not further reduced and even increased.</p><p><b>CONCLUSION</b>In patients with borderline systolic hypertension, the adaptive responses of the radial artery compliance and distensibility to increased pressure were directed to maintain its elasticity, contributing to the homeostasis of the cardiovascular system.</p>

Slow Atrioventricular Nodal Pathway Ablation: Electrocardiogram Monitoring During Effective Delivery of Radiofrequency Energy / 中山大学学报(医学科学版)

【Objective】 To explore the significance of electrocard iogram monitoring during the effective application of radiofrequency energy to s low atrioventricular (AV) nodal pathway ablation. 【Methods】 Slow AV nodal pathway ablation was performed in 58 patients with slownfast AV nodal ree-trant tachyca rdi a (AVNRT). The changes of electrocardiogram were monitored during the effective application of low radiofrequency RF energy (15～25 W). A faster rate of junctio nal ectopy (>150 min-1), ventriculoatrial (VA) block in association with j unctional ectopy, and l ong P-R interval during sinus beat were considered as harbingers of atrioventri cular (AV) block. RF energy deliveries were discontinued as soon as the harbinge rs of AV block occurred. Otherwise, RF energy continued until junctional ectopie s were decreased or vanished. If junctionnal ectopies were not decreased, RF ene rgy continued lasted for 90～120 s. 【Results】 Slow AV nodal pathway ablation w as successful in all patients who had junctional ectopy during the effective del ivery of RF energy. The effective ablation time was (128±26) s. 54 patients exp erienced one time successful ablation, and 4 patients experienced two times abla tion. Unsustained AV block occurred in 6 patinets after RF energy deliveries whi ch were immediately terminated because of VA block in association with junctiona l ectopy in 4 patinets and long P-R interval during sinus beats in 2 patients. No patients developed permanent AV block. Recurrent AVNRT requiring second ablat ion occurred in 2 of 58 successfully ablated slow pathway during (18±16) months of follow-up. 【Conclusion】 RF energy deliveries could be instructed b y intracardiac electrocardiogram monitoring during AVNRT ablation, which could e nhance the successful rate of slow pathway ablation, reduce recurrence and avoide permanent AV block.

Role of ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H_2O_2 preconditioning / 中国病理生理杂志

AIM: To explore the role of extracellular signal-regulated kinases ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H2O2 preconditioning in PC12 cells.METHODS: In PC12 cells,the experimental model of cytoprotection by H2O2 preconditioning against oxidative stress-induced injury was set up.The morphological changes in the apoptotic cells were observed by using of chromatin dye Hoechst 33258.The percent of apoptotic cells was determined by flow cytometry(FCM) with propidium iodide staining.The levels of p-ERK1/2 and p-STAT3 expression were detected by Western blotting assay.RESULTS: Preconditioning with H2O2 at concentration of 100 ?mol/L for 90 min obviously inhibited apoptosis induced by 300 ?mol/L H2O2,and both ERK1/2 and STAT3 were activated.UO126(10 ?mol/L,an inhibitor of ERK1/2) or AG-490(10?mol/L,an inhibitor of JAK2) significantly blocked the cytoprotection effect of H2O2 preconditioning.Moreover,UO126(10 ?mol/L) also markedly inhibited the up-regulation of p-STAT3 expression by H2O2 preconditioning.CONCLUSION: H2O2 preconditioning activates ERK1/2-STAT3 signal pathway,which may be one of the mechanisms underlying H2O2 preconditioning-induced cytoprotection.

Complement activation in acute coronary syndromes / 中国病理生理杂志

AIM:To evaluate complement activation in patients with all forms of acute coronary syndromes(ACS)and to examine the relationship between the degree of complement activation and myocardial injury.METHODS:The subjects were divided into 2 groups:110 ACS patients(group ACS)and 18 healthy persons(group control).One hundred and ten patients with ACS were divided into 3 sub-group:51 patients with ST-segment elevated myocardial infarction(STEMI),28 patients with non-ST-segment elevated myocardial infarction(NSTEMI)and 31 patients with unstable angina(UA).Complement 3(C3),complement 4(C4),troponin T(TnT)as well as creatine kinase MB(CK-MB)were evaluated.RESULTS:Plasma C3 and C4 peak levels were significantly higher in patients with STEMI [(1 525?302)mg/L and(423?123)mg/L] and NSTEMI [(1 516?289)mg/L and(396?68)mg/L] than those in patients with UA [(1 275?172)mg/L and(356?91)mg/L] and the control subjects [(1 072?196)mg/L and(182?73)mg/L](P

Correlation between the effect of angiotensin-(1-7) on cardiac hypertrophy and extracellular signal-regulated kinase in pressure-overloaded rats / 中国病理生理杂志

AIM: To investigate the effects and mechanisms of angiotensin-(1-7) on cardiac hypertrophy in pressure-overloaded rats. METHODS: Ar at model of pressure-overloaded heart was induced by constriction of abdominal aorta. Seventy-five male Sprague Dawley rats were randomized to sham-operated group, model control group and angiotensin-(1-7) treatment group. They were treated with intravenous infusion of angiotensin-(1-7) (25 microgram/kg per hour) or saline by minipump. RESULTS: Abdominal aortic banding resulted in a significant increases in LVW/BW, myocardial angiotensinⅡlevels, and p-ERK1/2 expression. Angiotensin-(1-7) had no effect on aortic banding-induced increases in myocardial angiotensinⅡlevels, but it significantly attenuated aortic banding-induced increases in LVW/BW and p-ERK1/2 expression. CONCLUSION: Angiotensin-(1-7) attenuates the development of cardiac hypertrophy in pressure-overloaded rats. It may be associated with the inhibition of p-ERK1/2 expression in cardiac tissue.

Myelin-associated glycoprotein inhibits the differentiation and neurite growth of neural stem cells / 中国病理生理杂志

AIM:To observe the characterization in neural cells derived from the hippocampus of embryonic rats and to examine the effect of myelin-associated glycoprotein(MAG) on the proliferation,differentiation and neurite growth of neural stem cells(NSCs).METHODS:The hippocampus cells of embryonic rats were isolated and cultured in vitro.The expressions of nestin and doublecortin,the marks of NSCs,were observed by immunocytochemical method.The rate of proliferating cells was examined by BrdU immunocytochemistry.The average neuronal neurite length and the percentage of differentiated neurons were detected by immunocytochemistry staining.RESULTS:The hippocampus cells of 16 days old embryonic rats had the characteristics of NSCs.The percentage of differentiated neurons(?-tubulin Ⅲ-positive cells) was 18.17%?2.79% and the average neuronal neurite length was(136.27?33.66)?m,seven days after the differentiation initiated in vitro in control group.After NSCs were treated with MAG-Fc(200 ?g/L),the percentage of differentiated neurons and the average neurite length were decreased,respectively,to 10.05%?3.42%(P0.05).CONCLUSION:MAG-Fc inhibits the differentiation and neurite growth of the NSCs,but has no effect on the proliferation.