Effects of Ca2+on the releases of ET-1, NO and PGI2 from bovine coronary artery endothelial cells during hypoxia

AIM: To explore the mechanism of ET-1, NO and PGI² release from coronary artery endothelial cells(CAEC) induced by acute hypoxia. METHODS: Bovine coronary artery endothelial cells were cultured and [⁴⁵ Ca²⁺] was used to investigate the difference of calcium uptake between normoxia group and hypoxia group(3% O₂). The contents of ET-1, NO and PGI² in media of normoxia group, hypoxia group and hypoxia + verapamil group were measured 24 h after hypoxia. RESULTS: [ ⁴⁵ Ca²⁺] uptake by CAEC in hypoxia group was 1.9 times more than normoxia group(P< 0.01). Hypoxia + verapamil group released more PGI², ET-1 and less NO than hypoxia group(P< 0.05). CONCLUSION: Changes of ET-1, NO and PGI² releases during hypoxia may be caused by the inflow of Ca²⁺ into coronary artery endothelial cells.     

Effect of BQ123 on the voltage-gated K+ current of pulmonary artery smooth muscle cells of rats exposed to chronic hypoxia

AIM:To study the effect of BQ123 on voltage-gated K+ current in pulmonary artery smooth muscle cells (PASMCs) from chronic hypoxic rats. METHODS:Twelve age and body weight matched Wistar rats were randomly divided into control and chronic hypoxic group. Single PASMCs were obtained with acute enzyme (collagnaseⅠ plus papain) dispersing method. Using the whole cell patch-clamp technique in freshly isolated PASMCs from normorxic and hypoxic rats, the effects of ET-1 and BQ123, a selective ETA receptor antagonist, on voltage-gated K+ current were recorded. RESULTS:(1) ET-1 (10-8 mol·L-1) caused inhibition of K+ current in PASMCs from normoxic and hypoxic rats. The effect of ET-1 on K+ current in PASMCs from hypoxic rats was greater than that from normoxic rats ［+50 mV, percent inhibition were (71.04±6.58)% and (60.21±5.32)%, respectively, P<0.01, n=6］. (2) In normoxic PASMCs, neither BQ123 alone produced influence on the IKV (P>0.05, n=5), nor ETA receptor blockade had change of ET-1 mediated IKV inhibition. (3) In chronic hypoxic PASMCs, BQ123 significantly reduced the effect of ET-1 mediated IKV inhibition, from (28.49±6.69) pA/pF to (74.19±9.74) pA/pF at +50 mV (P<0.01, n=6). CONCLUSION:In normoxic condition, the effect of ET-1 on IKV of PASMCs is not mediated by BQ123, a selective ETA receptor antagonist. During exposure to chronic hypoxia, the inhibition of ET-1 on IKV of PASMCs is partly mediated by BQ123, namely, ETA receptor mediates the effect of ET-1 on IKV of chronic hypoxic PASMCs.     

Effects of metoprolol on cardiomyocyte apoptosis and caspase-12 activation after coronary microembolization in rats

AIM: To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-12 activation after coronary microembolization in rats. METHODS: 30 rats were randomized to sham-operated group (S group), coronary microembolization group (CME group) and metoprolol group. Coronary microembolization models were produced by injection of 42 μm microspheres (3000/0.1mL) into the left ventricle during 10 seconds ascending aorta occlusion in rats. The S groups were injected saline instead. Intravenous metoprolol was infused into the rats assigned to the metoprolol groups.Cardiomyocyte apoptosis was detected with in TUNEL staining. The activation of caspase-12 was measured by Western blotting analysis. Left ventricular ejection fraction (LVEF) was assessed by transthoracic two-dimensional echocardiography. RESULTS: ① LVEF was significantly decreased in CME group compared to S group (P<0.05). No statistical difference between the metoprolol group and CME group was observed. ②Compared with S group, the apoptosis rate of cardiomyocytes and the levels of activated caspase-12 proteins in CME group were significantly increased (all P<0.05). Compared with CME group, the apoptosis rate of cardiomyocyte and the levels of activated caspase-12 proteins in metoprolol group were significantly decreased (all P<0.05). CONCLUSION: Metoprolol inhibits the apoptosis of cardiomyocytes and the activation of caspase-12 after coronary microembolization.     

Effects of pituitary adenylate cyclase-activating polypeptide on cardiac remodeling in coronary atherosclerotic rabbits

AIM:To study the intervention effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on cardiac remodeling during the development of rabbit coronary atherosclerosis. METHODS:60 male New Zealand rabbits were equally divided into 3 groups randomly: control group (C group), atherosclerosis model group (A group) and PACAP intervention group (P group). At the 4th, 8th and 12th week, 5-6 cases of rabbits in each group were sacrificed, cardiac tissue with coronary arteries were harvested to make paraffin sections. The sections were stained with hematoxylin-eosin and van Gieson separately. The qualitative observation and/or quantitative analysis were made by light microscope. RESULTS:（1）There was no lesion in C group. For A group and P group, there were plaques in large epicardial coronary arteries and small coronary arteries; an impressive accumulation of collagen was also observed in myocardium. In P group, the lesions of small coronary arteries were less serious, and the degrees of perivascular and myocardial fibrosis also appeared to be less.（2）For A group, the wall-to-lumen ratios in small coronary arteries were significantly greater at the 12th week (2.58±1.54) than C group (1.34±0.58) and P group (1.39±0.48) （P<0.05）； and the width of cardiomyocyte (13.85 μm±2.27 μm) was already remarkably narrower than C group (14.68 μm±2.40 μm) at the 8th week (P<0.05) and narrower significantly than C group and P group at the 12th week. （3）There were not difference significantly between the above-related parameters of P group and C group (P>0.05). CONCLUSION:Structure changes exist in coronary arteries and myocardium during the development of rabbit coronary atherosclerosis, PACAP can inhibit the cardiac remodeling.     

Pathophysiologic changes of local ischemic coronary artery and cardiac muscle after ligating canine LAD

AIM: To evaluate the reliability of making a research model of coronary artery stenosis and local myocardial infarction reproduced in dog by ligating canine LAD. METHODS: We disparted 30 aged healthy cross-breed dogs ［(18.5±6.7) kg］ into three groups. The near part of the LAD through left minimal thoracic incision was ligated to interdict 25% (group A), 50% (group B), 75% (group C) of the flux, respectively. The changes of plasma endothelium-derived factors NO, ET-1, sP-selectin and CTnT were measured before ligation and at different time points after ligation. The expression of P-selectin gene in cardiac muscle was detected by Western blotting. The segments of distal parts of the ligated LAD were cut and pathological changes of the patches of topical cardiac muscle were observed by electronic microscope. RESULTS: After ligation, NO/ET-1, P-selectin and CTnT had significant changes in group B (P<0.05) and group C (P<0.01). The expression of P-selectin of cardiac muscle was highly up-regulated after ligating in B (50%) and C (75%) group, In C group animals, a typical far more intense expression pattern was found. Under electronic microscope, the endothelium and other structures of the LAD wall and ultrastructure of myocardial cells had obvious changes in later two groups, especially in group C. There were a typical stenosis of LAD and myocardial infarction. CONCLUSIONS: Ligating the LAD 75% severely damages the endothelial cell and cardiac muscle cells of local ischemic vessel and cardiac muscle, thus forms the typical local stenosis of coronary artery and myocardial infarction, such method is a safe and reasonable way for making a disease model for studying CABG in surgery.     

Effects of atorvastatin on nitric oxide,endothelin-1 and myocardial function in a rabbit model of acute myocardial infarction and reperfusion

AIM: To evaluate the effects of atorvastatin on nitric oxide(NO), endothelin-1(ET-1)and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion(AMI/R). METHODS: Twenty-four rabbits were randomized into 3 groups: 8 in AMI/R group, 8 in atorvastatin-treated group(5 mg·kg-1·d-1)and 8 in sham-operated group. Animals in the former two groups were subjected to 60 min of coronary occlusion followed by 120 min of reperfusion. Data on haemodynamics were collected. NO in blood sample, and in normal, and in infarcted reflow and no-reflow myocardium were evaluated respectively by nitrate reductase method. The levels of ET-1 in blood sample, and in normal, infarcted reflow and no-reflow myocardium were determined by radioimmunoassay. RESULTS: (1)Compared to the baselines, the heart rate(HR), systolic blood pressure(SBP), diastolic blood pressure(DBP), left ventricular systolic pressure(LVSP), maximal rate of increase and decline in left ventricular pressure(±dp/dtmax)and cardiac output(CO)in AMI/R and atorvastatin-treated groups were significantly declined, whereas left ventricular end-diastolic pressure(LVEDP)was increased after 60 min of coronary occlusion and 120 min of reperfusion(P<0.05 or P<0.01). However, in atorvastatin-treated group, LVSP, LVEDP, ±dp/dtmax and CO at the time point of 120 min of reperfusion recovered more significantly than those at the time point of 60 min of coronary occlusion(P<0.01), which was more significant than those in AMI/R group(P<0.05 or P<0.01). Compared to AMI/R group, the SBP and DBP were significantly heigher in atorvastatin-treated group(P<0.01).(2)In atorvastatin-treated group, the levels of ET-1 in blood sample were significantly lower than those in AMI/R group(P<0.01), and the levels of NO were significantly higher(P<0.01). Moreover, the levels of NO or ET-1 in infarcted reflow myocardium were significantly lower than that in AMI/R group(P<0.05 or P<0.01).(3)Atorvastatin could ameliorate myocardial function. CONCLUSION: Atorvastatin is effective in increasing NO and reducing ET-1 in blood plasma and local myocardium, and in protection of endothelial cells. Atorvastatin also has a beneficial effect on improving left ventricular function during acute myocardial infarction and reperfusion in rabbits.     

Effect of non-invasive ischemic preconditioning on nitric oxide/endothelin-1 imbalance and gas exchange impairment following limb ischemia reperfusion: a clinical study

AIM: To investigate the effects of non-invasive ischemic preconditioning on nitric oxide (NO)/endothelin-1 (ET-1) imbalance and gas exchange impairment following limb ischemia reperfusion in patients undergoing unilateral lower extremity surgery with tourniquet. METHODS: Twenty-seven patients aged 25-65 years, whose tourniquets duration varied from 1 h to 1.5 h and matched American Society of Anesthesiologists Physical Status Ⅰ-Ⅱ, were randomized into two groups: a control group (n=14) and a ischemic preconditioning group (IPC group, n=13) in which patients received three cycles of 5 min of ischemia/5 min of reperfusion before tourniquet inflation. Radial arterial blood gas, plasma malondialdehyde (MDA) and NO, serum ET-1 and interleukin-6 (IL-6) were measured just before tourniquet inflation(T0), 1 h after inflation(T1), and 0.5 h(T2), 2 h(T3), 6 h(T4), 24 h(T5) after tourniquet deflation. Meanwhile NO/ET-1 ratio, alveolar-arterial oxygen gradient (PA-aDO2) and intrapulmonary shunt (Qs/Qt) were calculated. RESULTS: In control group, arterial partial pressure of oxygen (PaO2) were decreased, while PA-aDO2 and Qs/Qt were increased significantly at T4 compared to the baselines at T0 (P<0.01). Plasma NO levels and NO/ET-1 ratios decreased gradually after tourniquets deflation and statistical significances were observed at T3 (P<0.01) with a valley at T4 (P<0.01) and recovered to baselines at T5. Serum ET-1, IL-6 and plasma MDA began to increase remarkably after T3 (P<0.05 or P<0.01), peaked at T4 and dropped slightly at T5. The changes above-mentioned could be well attenuated by the application of IPC (P<0.05 or P<0.01) except PaO2 (P>0.05). CONCLUSION: Clinical application of unilateral tourniquet within safe time limit (1.5 h) may lead to limb ischemia reperfusion and further pulmonary gas exchange impairment, which could be partially attenuated by the application of IPC via alleviating NO/ET-1 imbalance.     

Vascular dilation function is correlated to the level of hs-CRP and ET-1 in patients with coronary artery disease

AIM: To evaluate the correlations among vascular dilation function, high-sensiticity C-reactive protein(hs-CRP) and endothelin-1(ET-1) in patients with coronary artery disease. METHODS: Flow-mediated vasodilation (FMD) and nitroglycerin mediated dilation (NMD) were measured by high-frequency ultrasound in 65 patients with coronary artery disease and 33 cases in control group. hs-CRP and ET-1 were detected at the meantime. RESULTS: FMD and NMD were decreased significantly in patients with coronary artery disease compared with the control group, but in contrast, hs-CRP and ET-1 were increased in patients with coronary artery disease as compared with the control group. hs-CRP and ET-1 were negatively correlated with FMD and NMD, respectively (P<0.05), and FMD was positively correlated with NMD (P<0.01). CONCLUSION: Vasodilation dysfunction exists in patients with coronary artery disease, which may result from the enhancement of hs-CRP and ET-1.     

Chronic hypoxia altered the expression of ET-1 mRNA in response to acute hypoxia in pulmonary artery endothelial cells

AIM:To investigate the expression of ET-1 mRNA in porcine pulmonary artery endothelial cells cultured in normoxic and chronic hypoxic conditions, and their different responses to acute hypoxia were also evaluated.METHODS:Insituhybridization and image -analysis system were used. RESULTS:Acute hypoxia enhanced the expression of ET-1 mRNA in both normoxic and chronic hypoxic group. The increment was more significant in the latter group.CONCLUSION:Chronic hypoxia increased the expression of ET-1 mRNA in response to acute hypoxia in porcine pulmonary artery endothelial cells.     

Correlation of urinary liver-type fatty acid binding protein concentration with renal injury in aged patients undergoing percutaneous coronary intervention

ATM: To determine whether urinary liver-type fatty acid-binding protein (uL-FABP) levels are related to acute renal injury and prognosis of renal (90 d) in the aged patients undergoing percutaneous coronary intervention (PCI). METHODS: The patients with age 60 or older undergoing PCI (n=48) were selected to conduct a prospective study. There were 14 patients with the occurrence of renal injury after PCI[renal injury was defined as an increase in serum creatinine (sCr) of greater than 20 μmol/L within 48 h after PCI]. uL-FABP was measured before PCI and at 6 h, 24 h and 48 h after PCI by ELISA. Correlation of the changes of sCr and estimated glomerular filtration rate (eGFR) after PCI with the uL-FABP levels was analyzed. RESULTS: uL-FABP increased significantly at 24 h and 48 h after PCI(P<0.05). However, sCr was only significantly increased at 48 h after PCI (P<0.05). The levels of uL-FABP before PCI and at 48 h after PCI were all significantly correlated with the increases of sCr within 48 h after PCI (P<0.01). No signifi-cant correlation between uL-FABP levels and the changes of eGFR following PCI (90 d) was observed. CONCLUSION: The increase in uL-FABP at 24 h after PCI in the aged patients may be an early indicator for acute renal injury as indicated by sCr at 48 h following PCI. Measurement of uL-FABP before PCI in the aged patients with occurrence of renal injury may be an important indicator for renal damage within 48 h.     

Changes of OX40 ligand expression in patients with acute coronary syndromes

AIM: To investigate the changes of OX40 ligand expression on monocytes and serum soluble OX40 ligand in patients with acute coronary syndromes (ACS).METHODS: The present study included healthy controls (n=30), patients with stable angina (SA, n=40) and patients with ACS, including unstable angina (UA, n=50) and acute myocardial infarction (AMI, n=30). The expression of OX40L on platelets was analyzed with flow cytometry and serum level of soluble OX40L (sOX40L) was determined with ELISA.RESULTS: The expression of OX40L on monocytes and serum level of sOX40L were significantly higher in patients with UA and AMI compared to healthy controls and patients with SA. In patients with AMI, sOX40L levels showed no significant increase when compared to patients with UA, while AMI patients had a peak level of sOX40L at 24 h after AMI. Percutaneous transluminal coronary angioplasty (PTCA) induced a marked rise in sOX40L levels in all patients. However, OX40L expression on monocytes showed no difference between patients with PTCA, before and after operation.CONCLUSION: The expression of OX40L may participate the mechanism of ACS and represent a marker for the activity of coronary disease.     

Relationship between serum concentrations of IL-18, IL-10, IL-6 and acute coronary syndrome

AIM: To examine the relation between serum concentrations of interleukin-18, interleukin-10, interleukin-6 and acute coronary syndrome (ACS). METHODS: Serum concentrations of IL-18, IL-10, IL-6 were measured in 17 patients with acute myocardial infarction (AMI), 30 patients with unstable angina pectoris (UAP), 15 patients with stable angina pectoris (SAP) and 20 controls by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA).The relation between IL-18, IL-6 and IL-10 was compared. RESULTS: Serum concentrations of IL-18, IL-6 were significantly increased in the AMI and UAP groups in comparison with the SAP and control groups. Conversely, serum concentrations of IL-10 were significantly decreased in the AMI and UAP groups in comparison with the SAP and control groups. The correlation of concentrations of IL-18 and IL-6 had no significance; but the levels of IL-18 and IL-6 were negatively correlated with IL-10. CONCLUSION: Serum IL-18, IL-6 concentrations increase while serum IL-10 concentration decreases in patients with acute coronary syndromes. The inflammatory imbalance between IL-18, IL-6 and IL-10 may play an important role in the instability of atherosclerotic plaque.     

Effects of Chinese medicine WPY on expression of L-selectin and distribution of F-actin in leukocytes from acute necrotizing pancreatitis rats

AIM: To explore the changes of L-selectin expression and F-actin distribution of leukocytes from pancreatic circulation in the experimental acute necrotizing pancreatitis (ANP) rats and impact of Chinese herbs west China pancreatitis yi hao (WPY) on them in vivo. METHODS: Forty-four Wistar rats were randomized into control group, ANP group and ANP WPY treated group. The leukocytes from blood of splenic vein were incubated with PE-anti-CD62L for L-selectin and TRTIC-Phalloidin for F-actin, then the ratio of CD62L positive granulocytes was measured by flow cytometry and leukocytes were taken images with confocal laser scanning microscope. The distribution of F-actin at the border or central part of leukocyte was analyzed by using Mias system. RESULTS: The ratio of CD62L positive granulocytes increased in ANP rats, but those increases at 6 h (31.78%±12.37%) and 12 h (29.83%±13.73%) were significant ［vs control group(11.96%±5.32%), P<0.05］. The ratio of F-actin border/center gray value of leukocytes increased at 1 h, 6 h and 12 h in ANP rats, and those at 1 h (2.52±0.49) and 12 h (2.72±0.48) were significant ［vs control group (1.79±0.26), P<0.05］. The ratio of F-actin border/center gray value of leukocytes (1.54±0.24) declined significantly at 6 h in WPY-treated ANP rats (P<0.05). CONCLUSION: L-selectin expression and F-actin distribution change significantly in leukocytes from pancreatic circulation in ANP rats, suggesting that an increase in adhesive avidity and a decrease in deformability of leukocytes are pathophysiologic factors for progression of ANP, and traditional Chinese medicine WPY may regulate these changes of leukocytes in some degrees.     

Role of endothelin in portal hypertension induced by endotoxin

AIM:To study the role of endothelin-1 (ET-1) in portal hypertension (PHT) induced by endotoxin. METHODS:Collagenase in situ perfusion was adopted to separate hepatic stellate cells (HSCs). HSCs was cultured on concretized collagen. ET-1 anti-sense oligonucleotide was added into the culture medium and then LPS was also added up to the concentration of 1 000 μg/L. The diameters of the concretized collagen were measured. Sense and mis-sense oligonucleotide were applied as control. ET-1 in the culture medium was detected by radioimmunoassay and ET-1 mRNA in HSCs was detected by RT-PCR. β-actin of HSCs was detected by Western blotting. RESULTS:The diameter of concretized collagen on which HSCs pretreated with ET-1 anti-sense oligonucleotide was 93.3%±3.8% the size of the primary. The diameter of concretized collagen of the control groups were 70.1%±4.8% and 70.5%±3.9% (P<0.05). ET-1 was (49.8±7.4)ng/L in the culture medium of HSCs pretreated with ET-1 anti-sense oligonucleotide and (329.8±34.9), (339.1±43.7)ng/L in the control medium (P<0.05). β-actin and ETI mRNA presented in HSCs pretreated with ET-1 anti-sense oligonucleotide was much less than that in the controls. CONCLUSION:ET-1 anti-sense oligonucleotide inactivated HSCs by counteracting the expression of ET-1, which may be helpful to control PHT induced by LPS.     

Changes in endogenous nitric oxide and effects of inhaled nitric oxide on pulmonary artery hypertension in chronically hypoxic rats

AIM: To investigate the role of nitric oxide (NO)in the development of chronically hypoxic pulmonary artery hypertension (PAH) and the hemodynamic effects of inhaled NO on pulmonary circulation. METHODS: 67 male adult SD rats were randomly divided into 7 groups: (1) control (n=9);(2) chronically intermitent hypoxia (CIH, 6 h/d, 7 d/w) 1 week(n=7); (3) CIH 2 weeks (n=11); (4) CIH 3 weeks (n=11); (5) CIH 1 week+L-NAME (NO synthase inhibitor, 30 mg/kg, by gavage, n=10); (6)CIH 3 weeks+L-Arg (NO precursor, 10 mg/kg, by gavage, n=9); (7) CIH 3 weeks+inhaled NO (0.0004% for 20 min, n=10) to determine the mean pulmonary artery pressure (MPAP), weigh the right ventricle (R) and ventricular segment plus left ventricle (S+L), and calculate R/(S+L) (g/g) and R/Wt (Wt: body weight, g/kg). RESULTS: 1.MPAP increased compared with control when CIH 1 week, reaching the highest when CIH 2 weeks; R/(S+L) and R/Wt also increased notably when CIH 1 week (P＜0.01); 2. The level of plasma NO₂^-/NO₃^- elevated significantly when CIH 2 weeks, but fell when CIH 3 weeks; the content of plasma ET-1(endothelin-1) also increased significantly. The level of plasma ET-1 correlated with R/(S+L) and R/Wt, r=0.43 and 0.46, respectively, both P＜0.01; 3. The level of plasma NO₂^-/NO₃^- droped 33.2 % (P＜0.01) after treatment with L-NAME, with R/(S+L) increasing 15.2 % (P＜0.05); 4. L-Arg decreased the MPAP 17.8 %(P＜0.01). CONCLUSION: The endogenous NO release increases at early stage (1-2 weeks) of chronic hypoxia, but falls at the prolonged stage; the elevated level of plasma ET-1 possibly plays an important role in remodeling of chronically hypoxic pulmonary vessels and ventricle; inhaled NO significantly decreases the chronically hypoxic PAH.     

Effects of endothelin and endothelin receptor antagonist on funny current and its gene expression in neonatal rat ventricular myocytes

AIM: To analyze the effect of endothelin-1 (ET-1) and ET-1 receptor antagonist on funny current (If) and its gene (hyperpolarization-activated cation channel, HCN) expression in neonatal rat ventricular myocytes. METHODS: Fresh ventricular myocytes were isolated from 1-3 d rats. The expression of If gene was measured by real-time quantitative polymerase chain reaction (real-time PCR). If was recorded and studied through whole-cell patch clamp. The cardiomyocytes were stimulated by ET-1 (0, 1, 10, 100 nmol/L) for 3 hours, or ET-1 (100 nmol/L) for 0, 0.5, 1, 3, 6 hours or ET-1 plus ETA- or ETB-receptor antagonist (BE-18257B or IRL-1038), respectively. RESULTS: HCN1, HCN2, HCN3, HCN4 represented (0.23±0.01)%, (83.58±0.04)%, (0.79±0.01)%, (15.44±0.01)% of total HCN mRNA, respectively. If was recorded. When cells were stimulated by ET-1 (10, 100 nmol/L), HCN2 was significantly increased by 0.1, 2 times and HCN4 was increased by 0.1, 0.5 times. When cells were stimulated for 0.5, 1, 3 and 6 hours, HCN2 was significantly increased by 0.3, 1, 5, 5.1 times and HCN4 was increased by 0.1, 0.6, 2, 2.1 times. The treatment of the combination of ET-1 plus BE-18257B significantly decreased HCN2 and HCN4 level. However, HCN1 and HCN3 had no statistically significant change. If would be increased by ET -1 and this effect was reverted by BE-18257B. IRL-1038 had no effects on If and HCN. CONCLUSION: (1) HCN2 and HCN4 represent a large amount of total HCN mRNA in neonatal rat ventricular myocytes. (2) If and the expression of HCN2 and HCN4 are increased by ET-1, this effect is reverted by BE-18257B.     

Inhibitory effect of high-dose Xuezhikang on inflammatory response induced by percutaneous coronary intervention in patients with unstable angina

AIM: To study the inhibitory effect of high-dose Xuezhikang,administered before percutaneous coronary intervention (PCI) on inflammatory response induced by PCI in patients with unstable angina (UA).METHODS: All patients with UA in class Ⅲ and ⅡB according to Braunwald classification were considered for inclusion in the present study.Finally,196 patients received Xuezhikang treatment 72 h before coronary angiography and successfully performed PCI with elevated C-reactive protein (CRP) level (>3 mg/L) were randomised to 2 groups: 1.2 g/d of Xuezhikang as group A,or 2.4 g/d of Xuezhikang as group B.The levels of CRP were measured at baseline,after 3 days of therapy (before procedure) and 48 hours after PCI.The patients were followed-up for 6 months for major adverse coronary events and left ventricular ejection fraction.RESULTS: There was no significant difference in the mean CRP level among the two randomized groups (P>0.05),however,after three days of pharmacological treatment,there was significantly reduced CRP content in group A ［(5.44±1.57） mg/L vs （4.04±1.54） mg/L,P<0.05］ and in group B ［(5.42±1.36） mg/L vs （3.60±1.14） mg/L,P<0.05］ compared with admission.Measurements performed 48 hours after the procedure revealed a marked CRP level increase in group A (up to 9.22 mg/L±5.03 mg/L) and an obvious increase in groups B (up to 4.97 mg/L±1.75 mg/L,P<0.05) compared with pre-procedure.The serum level of CRP in B group was distinctly lower than that in A group before (P<0.05) and after the procedure (P<0.05),respectively.Major adverse coronary events during the 6-month clinical follow-up occurred less in group A than that in group B ［21/104 (20.2%) vs 9/92 (9.8%); patients,P<0.05］.Follow-up echocardiography revealed lower left ventricular ejection fraction in group A than that in group B (55.41%±10.93% vs 59.30%±9.99%,P<0.05).CONCLUSION: High-dose Xuezhikang therapy,administered before PCI,has better inhibition effect than low-dose on inflammatory response induced by PCI in patients with UA.Attenuation of inflammatory response may be crucial for the reduction of coronary events following invasive coronary interventions.     

Changes of serum nitric oxide in CB4V-induced insulin-dependent diabetic mice

AIM: To observe the changes of serum nitric oxide and the production level of IL-1 in different period of coxsackievirus B4 (CB₄V)-induced insulin-dependent diabetic mice.METHODS: The insulin-dependent diabetes mellitus (IDDM) animal model induced by CB₄V infection was established. Serum nitric oxide level was estimated by nitrate reductase method after infection 72 h,1 week, 3 weeks,6 weeks,8 weeks, respectively. At the same time, level of IL-1 produced by peritoneal Mф was measued.RESULTS: (1) Changes of serum nitric oxide: serum nitric oxide level in control group remained normal level. The serum nitric oxide level in diabetic group increased significantly at 72 h after infection(P＜0.01), and reached top at 1 weeks after infection, then decreased to normal level in 6 and 8 weeks (P＞0.05). (2) IL-1 activities: IL-1 activities were increased obviously from 72 h to 3 weeks after virus infection, but decreased to normal level after 6 weeks.CONCLUSION: Nitric oxide may be one of the important factors in the development of CB₄V-induced IDDM.     

Effect of ischemia/reperfusion on expression of endothelin in the rat ventral prostate and preventive measure

AIM:Effect of ischemia/reperfusion on expression of endothelin-1(ET-1) in the rat prostate and preventive measure were studied. METHODS:The abdominal aorta of rat was clipped briefly and repeatedly so as to treat the prostate with ischemia/reperfusion and expression of ET-1 mRNA in the ventral prostate was determined by RT-PCR.RESULTS:Expression of ET-1 mRNA in the ventral prostate was significantly increased at 1 h and 3 h after 90 min repeated ischemia/reperfusion (P＜0.05), and was not significantly changed after previous treatment of Dizocilpine maleate (MK-801) (P＞0.05). CONCLUSIONS:Expression of ET-1 in the prostate can be affected by repeated brief ischemia/reperfusion and it may play a role in the development of benign prostatic hyperplasia. Ischemia-reperfusion-induced ET-1 expression in the prostate of rats can be inhibited by prectreatment of MK-801.