[Short-term prognosis and risk factors of ventricular septal rupture following acute myocardial infarction].

OBJECTIVE: To analyze the short-term prognosis and risk factors of ventricular septal rupture (VSR) following acute myocardial infarction (AMI). METHODS: A total of 70 consecutive VSR patients following AMI hospitalized in our hospital from January 2002 to October 2010 were enrolled in this study. We compared the clinical characteristics of patients with VSR who survived ≤ 30 days (n = 39) and survived > 30 days (n = 31) post AMI. A short-term prognosis index of VSR (SPIV) was established based on the logistic regression analysis. RESULTS: The single factor analysis showed that the risk factors of death within 30 days of VSR patients were female, anterior AMI, Killip class 3 or 4, apical VSR and non-aneurysm (all P < 0.05). Logistic regression analysis revealed that female (P = 0.013), anterior AMI (P = 0.023), non-aneurysm (P = 0.023), non-diabetes (P = 0.009), Killip class 3 or 4 (P = 0.022) and time from AMI to VSR less than 4 days (P = 0.027) were independent risk determinants for death within 30 days post VSR. Patients with SPIV ≥ 9 were associated with high risk [77.4% (24/31)] of dying within 30 days post AMI. SPIV ≤ 8 were associated with low risk as the 30 days mortality is 28.6% (8/28). CONCLUSION: Female gender, anterior AMI, non-aneurysm, non-diabetes, Killip class 3 or 4 and time from AMI to VSR less than 4 days are independent risk factors of short-term mortality of VSR.

[Real world thirty-day mortality in female patients with acute myocardial infarction from Beijing].

OBJECTIVE: To evaluate the gender differences on the short-term outcomes of patients with acute myocardial infarction in the real world. METHODS: A total of 471 consecutive patients [male 368(78.1%) and female 103(21.9%)] with acute myocardial infarction <72 hours in cardiac care unit were included. The clinical data, death and major adverse cardiac and cerebrovascular events at 30 days post hospitalization were analyzed. RESULTS: Female patients were older (66.8 ± 10.1 vs. 56.9 ± 12.0, P < 0.001), TIMI score (5.1 ± 2.3 vs. 3.9 ± 2.1, P < 0.001) and GRACE score (162 ± 39 vs. 142 ± 35, P < 0.001) in female patients were higher than in male patients. Female patients had lower proportion of stent implantation (P = 0.038) while higher percentage of complex lesions and contraindications to PCI (P = 0.015) compared to male patients. Proportion of cardiac rupture, mitral regurgitation, malignant arrhythmia, post-infarction angina pectoris, contrast-induced nephropathy and minor gastrointestinal bleeding were also higher in female patients tan in male patients (P < 0.05). Thirty-day mortality was significantly higher in female patients than in male patients [5.8% (6/103) vs. 1.9% (7/368), P = 0.032], MACCE [10.7% (11/103) vs. 5.4% (20/368), P = 0.058] also tended to be higher in female patients than in male patients. Multi-logistic regression analysis showed that female gender was not an independent predictor for thirty-day mortality (P = 0.141) or MACCE (P = 0.426) while systolic blood pressure (OR = 1.072, 95%CI:1.016-1.130, P = 0.010) and pericardial effusion after myocardial infarction (OR = 40.518, 95%CI:1.098-1495.702, P = 0.044) were independent predictors for thirty-day mortality while systolic blood pressure (OR = 1.027, 95%CI:1.002-1.052, P = 0.036) and left ventricular ejection fraction (OR = 1.108, 95%CI:1.032-1.190, P = 0.005) were independent predictors for MACCE. CONCLUSIONS: Female gender itself is not an independent predictor for thirty-day mortality and MACCE despite poorer clinical characteristics, higher incidence of complications, and worse prognosis in female patients.

[Impact of cytochrome P450 2C19 polymorphisms on outcome of cardiovascular events in clopidogrel-treated Chinese patients after percutaneous coronary intervention].

OBJECTIVE: To investigate the impact of cytochrome P450 (CYP) 2C19 681G > A polymorphism on long-term prognosis of clopidogrel-treated Chinese patients after percutaneous coronary intervention (PCI). METHODS: Between January 1, 2009 and August 31,2009, 267 patients with coronary heart disease who received PCI and treated with clopidogrel for 12 months were enrolled. CYP2C19 * 2 was detected by MALDI-TOF MS and patients were grouped into CYP2C19 * 1/ * 1 (n = 130) and CYP2C19 * 2 carriers group (n = 137). Follow-up was 12 months. The primary endpoint was angina recurrence, urgent coronary revascularization, acute myocardial infarction, stent thrombosis, death and the combined end points. RESULTS: Baseline data were similar between two groups (P > 0.05). Urgent coronary revascularization and the combined end points occurred more frequently in CYP2C19 * 2 carriers than in CYP2C19 * 1/* 1 patients (7.3% vs. 1.5% and 8.0% vs. 2.3% respectively, all P < 0.05). But incidence of angina recurrence, acute myocardial infarction, stent thrombosis and death was similar between two groups (all P > 0.05). Hazard risk of 1 year cumulative survival of CYP2C19 * 2 carriers group was significantly higher than CYP2C19 * 1/ * 1 group after PCI ( HR = 3.59, 95% CI: 1.02 - 12.87, P < 0.05). CONCLUSION: CYP2C19 681G > A polymorphism is a determinant of prognosis in coronary heart disease patients receiving chronic clopidogrel treatment after PCI.

[Clinical characteristics and outcome comparison between young (< or = 45 years) female and male patients with coronary artery disease undergoing percutaneous coronary intervention].

OBJECTIVE: To compare the clinical characteristics and clinical outcomes in young (< / = 45 years) female and male coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). METHODS: Angiographic and clinical data from 124 premenopausal female patients who underwent elective PCI from April 2004 to February 2008 were compared to age-matched 430 male patients who underwent elective PCI between 2006 and 2007 in our department. All patients were treated according to guidelines and coronary angiography was repeated after 6 months. One year clinical follow-up were performed in all patients. RESULTS: Incidences of dyslipidemia, the history of myocardial infarction and smoking were significantly lower in female patients than in male patients (all P < 0.01). Left main, left anterior descending and bifurcation lesions were more common while type C lesion and right coronary lesion were less common in young female CAD group compared to young male CAD group (P < 0.01-0.05). The average lesion length in female patients was significantly longer than that in male patients [(20.36 +/- 13.37) mm vs. (23.04 +/- 13.86) mm, P < 0.05]. The in-hospital and follow-up incidences of major adverse cardiac events, stent thrombosis and in-stent restenosis were similar between young female and male CAD patients. CONCLUSIONS: CAD risk factors were less and vessel lesions were more likely to be found at left main, left anterior descending and bifurcation in young female CAD patients compared to young male CAD patients. The clinical outcomes were similar between young female and male CAD patients.

[The relationship between plasma BNP level and the left ventricular dysfunction parameters in patients with acute myocardial infarction and it's value in diagonosing heart failure.].

OBJECTIVE: To explore the correlation between plasma BNP level and left ventricular dysfunction parameters in patients with acute myocardial infarction (AMI). METHODS: Plasma BNP level was determined in 230 consecutive inpatients with AMI and 111 normal controls. Patients were grouped according Killip grades, LVEF and LVEDd, respectively. BNP was transformed into lnBNP for the normal distribution. The receiver operator characteristic curve (ROC curve) was drawn to determine the best threshold and criteria for diagnosing heart failure. RESULTS: After AMI, lnBNP levels increased significantly in proportion with increasing Killip grades (I-III), and decreasing LVEF (all P < 0.05). lnBNP level was significantly higher in LVEDd > 55 mm group than in the LVEDd < 55 mm group (P < 0.01). lnBNP, LVEDd and LVEF all linearly correlated with Killip grades (P < 0.05) and the best correlation was shown between lnBNP and Killip grades (r = 0.53, P < 0.05). lnBNP also positively correlated with LVEDd (r = 0.17, P < 0.05) and negatively correlated with LVEF (r = -0.41, P < 0.01). Among the parameters, lnBNP level presented the largest AUC in their ROC curves (P < 0.01) for diagnosing decompensated heart failure and cardiogenic shock. The sensitivity, specifiticity and accuracy rates for diagnosing decompensated heart failure were 84.9%, 45.0% and 70.0% respectively by lnBNP at the cut point of 140 ng/L. The sensitivity, negative predicting value and accuracy rate for diagnosing cardiac shock were 82.8%, 66.7% and 67.4% respectively by BNP at the cut point of 400 ng/L. CONCLUSION: lnBNP level in hospitalized patients with AMI was positively correlated with Killip grades and LVEDd, negatively correlated with LVEF and could serve as a parameter for diagnosing the decompensated heart failure and excluding the cardiac shock.

[Effect of intracoronary transplantation of autologous bone marrow mononuclear cells on myocardial ischemia reperfusion injury in mini-swine model].

OBJECTIVE: To investigate the therapeutic effectiveness of intracoronary transplantation of autologous bone marrow mononuclear cells (BM-MNC) on myocardial ischemia reperfusion injury in mini-swine model. METHODS: Myocardial ischemia reperfusion injury model was established by ligating in 16 mini-swines, which were further randomized into two groups: (3.54 +/- 0.90) x 10(8) BM-MNC was intracoronarily transplanted in BM-MNC group (n = 9), and phosphate buffer saline was intracoronarily applied in the control group (n = 7). Ultrasonic cardiograhpy, hemodynamics, neovascular density, and myocardium infarction size were evaluated before and 4 weeks after transplantation. RESULTS: In BM-MNC group, left ventricular ejection fraction (LVEF), intra-ventricular septa, lateral wall and anterior wall, cardiac output (CO) and + dp/dt(max) had no significant differences before and 4 weeks after transplantation (P > 0.05). In the control group, LVEF, intraventricular septa, lateral wall and anterior wall, CO, and + dp/dt(max) significantly decreased 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and- dp/dt(max) had no significant differences before and after cell transplantation. Capillary density was significantly larger in the BM-MNC group than in the control group [(13.39 +/- 6.96) /HP vs. (3.50 +/- 1.90) /HP]. The percentage and size of myocardial infarction was significantly lower in the BM-MNC group than in the control group. CONCLUSION: Transplantation of BM-MNC into the myocardial ischemic reperfusion-injury area can increase capillary density and decrease infarction area, and thus remarkably improve cardiac systolic function.

Post-infarction treatment with simvastatin reduces myocardial no-reflow by opening of the KATP channel.

UNLABELLED: Simvastatin can prevent cardiac remodelling after myocardial infarction, though the exact mechanisms are uncertain. Myocardial no-reflow is associated with progressive cardiac remodelling. However, it remains unknown whether post-infarction treatment with simvastatin can also reduce myocardial no-reflow for which suppression of adenosine triphosphate-sensitive K+ (K(ATP)) channel opening is an important mechanism. METHODS: Area at risk and the area of no-reflow were determined by myocardial contrast echocardiography (MCE) and by pathology in 45 mini-swine randomised into 5 groups: 10 control, 9 simvastatin, 9 glibenclamide, 9 simvastatin plus glibenclamide and 8 sham-operated. A myocardial infarction and reperfusion model was created by 3-h occlusion of the coronary artery followed by 4 weeks of reperfusion. RESULTS: Compared with the control group, simvastatin significantly increased coronary blood volume (P<0.01) and decreased the area of no-reflow measured by MCE (78.5+/-4.5% to 43.7+/-4.3%) and pathological evaluation (82.3+/-1.9% to 45.2+/-3.8%) of area at risk (P<0.01). Simvastatin also increased the levels of K(ATP) channel proteins (SUR2 and Kir6.2) (P<0.05), but had no effect on necrosis area. The combination of simvastatin and glibenclamide had no significant effect on the above parameters. CONCLUSIONS: Post-infarction treatment with simvastatin can reduce myocardial no-reflow. This beneficial effect is due to activation of the K(ATP) channel.

Inferior-septal myocardial infarction misdiagnosed as anterior-septal myocardial infarction: electrocardiographic, scintigraphic, and angiographic correlations.

OBJECTIVE: To explore the infarct sites in patients with inferior wall acute myocardial infarction (AMI) concomitant with ST segment elevation in leads V1-V3 and leads V3R-V5R. METHODS: Five patients diagnosed as inferior, right ventricular, and anteroseptal walls AMI at admission were enrolled. Electrocardiographic data and results of isotope 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging and coronary angiography (CAG) were analyzed. RESULTS: Electrocardiogram showed that ST segment significantly elevated in standard leads II, III, aVF, and leads V1-V3, V3R-V5R in all five patients. The magnitude of ST segment elevation was maximal in lead V1 and decreased gradually from lead V1 to V3 and from lead V1 to V3R-V5R. There was isotope 99mTc-MIBI myocardial perfusion imaging defect in inferior and basal inferior-septal walls. CAG showed that right coronary artery was infarct-related artery. CONCLUSIONS: The diagnostic criteria for basal inferior-septal wall AMI can be formulated as follows: (1) ST segment elevates > or = 2 mm in lead V1 in the clinical setting of inferior wall AMI; (2) the magnitude of ST segment elevation is the tallest in lead V1 and decreases gradually from lead V1 to V3 and from lead V1 to V3R-V5R. With two conditions above, the basal inferior-septal wall AMI should be diagnosed.

[The predictive value of B-type natriuretic peptide for the mortality from acute myocardial infarction].

OBJECTIVE: To explore the predictive value of B-type natriuretic peptide (BNP) for the mortality of acute myocardial infarction (AMI). METHODS: Follow-up was made in 264 consecutive patients with AMI, with an average period of (14.7 +/- 5.3) months and follow-up rate of 87.1% (230 cases). Cardiac death was recorded in the 1st, 6th and 12th month after AMI. Among one to seven days after AMI, the MB isoenzyme of creatine kinase (CK-MB), troponin T (TnT), echocardiographically measured left ventricular end-diastolic internal diameter (LVEDd), left ventricular ejection fraction (LVEF) and BNP were determined. The Receiver Operating Characteristic (ROC) were drawn to determine the predictive value for the cardiac death after AMI comparing BNP with the classical risk factors mentioned above. Analysis was made to define the relative independent risk factors of cardiac death and non-cardiac death survival rate after AMI. RESULTS: The ROC curves comparing CK-MB, TnT, LVEDd and LVEF with BNP and lnBNP showed that BNP was the only index for predicting cardiac death after AMI, the cut off point value of BNP determined according to ROC curve was 864 ng/L and the sensitivity, specificity, accuracy, positive and negative predictive values for predicting the cardiac death was 76.2% - 92.9%, 84.3% - 85.6%, 82.2% - 86.1%, 21.3% - 36.2% and 97.3% - 98.9% at the 1st 16th, 12th month after AMI respectively. Furthermore, BNP showed the only independent risk factor for predicting the cardiac death in the short and long term period after AMI (P < 0.01) by multiple factors cox regression analysis. The non-cardiac death survival rate in the group of BNP level < or = 864 ng/L was significantly higher than that in the group of BNP > 864 ng/L (97.3% vs 72.3%, P < 0.001), and the median survival time of the dead in the former group was also significantly longer than in the latter group (16.0 vs 10.7, P < 0.01), no matter whether they were suffering from AMI with ST elevation or not, treated with or without primary PCI. CONCLUSION: BNP has the best predictive value for mortality after AMI compared with other traditional indexes.

[Autologous bone marrow mononuclear cells and peripheral endothelial progenitor cells differentiation in myocardial ischemia reperfusion injury region in swine].

OBJECTIVE: To investigate the differentiation status of autologous bone marrow mononuclear cells (BM-MNC) and peripheral endothelial progenitor cells (EPC) transplanted into myocardial ischemia reperfusion injury region in swine. METHODS: BM-MNC marked with PKH26 (n = 9), EPC marked with CM-DiI (n = 7), phosphate buffer saline (control, n = 7) were transplanted into myocardial ischemia reperfusion injury region of swine by intracoronary artery injection. Specimens were harvested 4 weeks after injection for histological analysis (HE, immunochemical stain for vWF, alpha-sarcomeric-actin and fibronectin antibody). Cell differentiation was observed under transmission electronmicroscope. RESULTS: The number of small blood vessels was similar between BM-MNC group and EPC group (13.39 +/- 6.96/HP vs.12.39 +/- 4.72/HP, P < 0.05), but was significantly higher than that of control group (P < 0.05). Responsive intensity of immunochemical stain for fibronectin antibody was significantly lower in BM-MNC and EPC groups than that in control group. Responsive intensity of immunochemical stain for alpha-sarcomeric-actin antibody was similar among the three groups. Cluster cells were observed in one swine from BM-MNC group which might relate to the proliferation of stem cells in situ. Immature endothelial cells and myocytes were also detected by transmission electronmicroscope in BM-MNC and EPC group. CONCLUSION: BM-MNC and EPC transplanted into myocardial ischemia reperfusion injury region in swine stimulated the formation of blood vessels and inhibited fibrogenesis.

[Effects of intracoronary transplantation of autologous bone marrow mononuclear cells or endothelial progenitor cells in mini-swine model of myocardial ischemia-reperfusion].

OBJECTIVE: To compare the effects of intracoronary transplantation of autologous bone marrow mononuclear cells (BM-MNC) or peripheral endothelial progenitor cells (EPC) in mini-swine model of myocardial ischemia-reperfusion. METHODS: The Mini-swine acute myocardial infarction and reperfusion model was created with 90 min occlusion of the left anterior descending coronary artery followed by reperfusion and the animals were then divided into BM-MNC group (3.54 x 10(8) +/- 0.90 x 10(8), n = 9), EPC group (1.16 x 10(7) +/- 1.07 x 10(7), n = 7) and control group (saline, n = 7). Echocardiography, hemodynamic measurements and myocardium infarction size were evaluated before and 4 weeks after intracoronary cell transplantations. RESULTS: The net decrease from baseline to 4 weeks after transplantation of left ventricular ejection fraction (LVEF), left ventricular end systolic pressure, cardiac output and +dp/dt(max) were significantly attenuated post BM-MNC and EPC therapy compared to control group (all P < 0.05) and were similar between BM-MNC and EPC groups. Transplantation of BM-MNC and EPC also significantly decreased myocardial infarction size compared to control group. CONCLUSION: Autologous intracoronary transplantation of BM-MNC or EPC in this model equally improved cardiac systolic function and reduced infarction area.

[Beneficial effects of carvedilol on cardiomyocyte apoptosis and bcl-2/bax expression after acute myocardial infarction an experiment with rats].

OBJECTIVE: To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction (AMI). METHODS: Eighty-three female SD rats underwent ligation of left anterior descending coronary artery, and were randomly assigned to 2 groups 24 hours later: carvedilol (n = 40, 10 mg.kg(-1).d(-1)was administered via direct gastric gavage 24 hs after the ligation, Group C) and AMI control group (n = 43, normal saline of the same volume was given by gastric gavage, Group MI). Another 27 rats were used as sham operation group (Group S, administered with normal saline too). The rats of each group were killed and their hearts were taken out 48 hours and 4 weeks after observation respectively (MI-48 h, MI-4 week, C-48 h, C-4 week, S-48 h, and S-4 week subgroups). TUNEL and DNA gel electrophoresis were used to detect the cardiomyocyte apoptosis. Immunohistochemistry and Western blotting were used to detect the expression of bcl-2 and bax. RESULTS: The apoptotic indices of the infracted/scar, border and non-infarcted areas at any time-point of Group MI were all significantly higher than those of Group S (all P < 0.05). Only the apoptotic indices of the infracted/scar and border areas of the C-4 week subgroup were significantly lower than those of the MI-4 week subgroup (both P < 0.05), and were close to those of the non-infarcted area. DNA gel electrophoresis showed that the positive rate of Group S at any time-point were both 0, the positive rate of MI-48 h subgroup and C-48 h subgroup were both significantly higher than that of Group S (both P < 0.05) without significant difference between these 2 groups, and the positive rates of the MI-4 week subgroup and C-4 week subgroup were both 0. Immunohistochemistry showed that the bax gene expression was slightly to significantly increased in the infarcted/scar, border, and non-infarcted areas of the MI-48 h and MI-4 week subgroups. The bcl-2 expression was significantly increased only in the infracted area of the MI-48 h subgroup. The bcl-2 expression was slightly increased in the infracted and border areas of the C-48 h subgroup and the bax expression was significantly decreased in the infracted/scar area of the C-4 week subgroup. Western blotting showed that (1) the bcl-2 expression of the S-4 week subgroup was significantly higher than that of the S-48 h subgroup (P < 0.05), (2) the bcl-2 expression and bax expression of the MI-48 h subgroup were significantly higher than that of the S-48 h subgroup (P < 0.05 - 0.01), the bcl-2/bax ratio of the MI-48 h subgroup was significantly lower that that of the S-48 h subgroup, however, there were no significant differences in the bcl-2 and bax expression and bcl-2/bax ratio between the MI-4 week subgroup and S-48 h subgroup (all P > 0.05), and (3) There were no significant difference in the bcl-2 and bax expression between Group A and Group S (all P > 0.05), however, the bcl-2/bax ratios at the 2 time-points of Group C were both significantly higher than those of Group MI. CONCLUSION: Cardiomyocyte apoptosis occurs in the infarction/scar, border and non-infarcted areas after AMI. Prolonged treatment with carvedilol reduces cardiomyocyte apoptosis in the scar and border areas and increases the expression ratio of bcl-2/bax.

[Effect of adenosine on endothelin-1 in the infarcted reflow and no-reflow myocardium of mini-swine].

OBJECTIVE: To evaluate the effect of adenosine on endothelin-1 (ET-1) after acute myocardial infarction (AMI) and reperfusion and explore the possible mechanism of no-reflow. METHODS: Twenty-four mini-swine were randomized into three study groups: control group (n=8), adenosine treated group (n=8), and sham-operated group (n=8). The mini-swine in the groups were subjected to 3 hours of coronary occlusion, followed by 60 minutes of reperfusion except those in the sham-operated group. The levels of ET-1 in blood sample, normal, infracted reflow and no-reflow myocardium were evaluated by radioimmuno-assay (RIA). The gene expressions of ET-1 in normal, infracted reflow and no-reflow myocardium were quantified by reverse transcription-polymerase chain reaction. RESULTS: In both control group and adenosine group, compared with that at the baseline, ET-1 in blood sample significantly increased at 5 minutes and 180 minutes of left anterior descending coronary artery occlusion, as well as 5 and 60 minutes of reperfusion (all P < 0.01). In adenosine group, the levels of ET-1 were significantly lower than those in the control group (P < 0.05, P < 0.01). In both control group and adenosine group, compared with that in normal myocardium, ET-1 levels in both infarcted reflow and no-reflow myocardium significantly increased (both P < 0.01), with the level of ET-1 in no-reflow myocardium significantly higher than that in infarcted reflow myocardium (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01). In both control and adenosine groups, compared with that in normal myocardium, the gene expression of ET-1 in infarcted reflow myocardium was significantly up-regulated (P < 0.01), while that of ET-1 in. no-reflow myocardium significantly down-regulated (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01). CONCLUSION: The endothelium injury may be one of the important mechanisms for no-reflow phenomenon. Adenosine cay prevent endothelium from injury to reduce no-reflow.

[Effects of atenolol and metoprolol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction in rats].

OBJECTIVE: To compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction (AMI) in rats. METHODS: AMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(-1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham operation group (group S, n = 27) was also established. Two subgroup (48 h subgroup and 4 weeks subgroup) was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry and Western blot analysis. RESULTS: Compared with AMI control group, myocyte apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01) in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of bax and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and bax were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group (P < 0.05). CONCLUSION: Both Atenolol and Metoprolol treatment can reduce cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.

[Serum B-type natriuretic peptide changes in patients with acute myocardial infarction].

OBJECTIVE: To observe the serum B-type natriuretic peptide (BNP) changes post acute myocardial infarction (AMI). METHODS: The serum BNP level was determined in 230 consecutive patients with AMI admitted to CCU and in 111 normal cases from October 2002 to October 2003 in Fuwai Hospital. The 230 AMI patients were further divided into various subgroups according to first or recurrent AMI, ST elevations myocardial infarction (STEMI) or non-ST elevations myocardial infarction (NSTEMI) group, infarction location, coronary arteries involved, infarction related arteries (IRA), TIMI blood flow of IRA and primary PCI or not. Serum BNP, CK-MB, TnT and heart function were analyzed. RESULTS: The serum BNP level was significantly increased in patients with AMI (553.7 +/- 735.1) ng/L than that in normal subjects [(26.4 +/- 27.4) ng/L, P < 0.05]. LVEF was significantly lower, and LVEDd, BNP and LnBNP were all significantly higher in the first time AMI group compared to recurrent AMI group (all P < 0.001). The BNP level were significantly higher in AMI patients with single or triple coronary arteries stenosis than those without coronary stenosis (P < 0.05), in TIMI blood flow 0 - 1 and 2 groups than in TIMI 3 group (all P < 0.001). The CK-MB and TnT were significantly increased while BNP significantly decreased in the patients underwent primary PCI group compared with patients did not receive PCI therapy (all P < 0.05 - 0.001). CONCLUSION: Serum BNP was significantly elevated in patients after AMI but decreased after successful primary PCI in patients with AMI.

[Effects of anti-platelet drugs on myocardial no-reflow after acute myocardial infarction and reperfusion: experiment with mini-swine model].

OBJECTIVE: To evaluate the effects of anti-platelet drugs on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion. METHODS: Thirty-two mini-swine were randomized into 4 equal groups: Control Group, without any intervention; Group A approximately C, pretreated with aspirin-clopidogrel (A-C) combination (300 mg loading dose followed by 75 mg per day of clopidogrel and 10 mg x kg(-1) x d(-1) of aspirin for 3 days), Group Tirofiban, given an intravenous infusion of tirofiban (15 microg/kg in intravenous bolus followed by 0.5 microg x kg(-1) x min(-1) in continuous intravenous infusion from 30 min before occlusion to the end of protocol; and Sham Operation Group, undergoing sham operation. The former 3 groups underwent three-hour occlusion of the left anterior descending (LAD) coronary artery followed by one-hour reperfusion Before the adminisfration of drngs and hefore lipation of LAD flood sanpks were collocfed to detoif the platelet aggregation rate (PAR). Hemodynamic examination and myocardial contrast echocardiography (MCE) were performed before AMI, 3 h after AMI, and 1 h after reperfusion. The coronary ligation area (LA) and area of no-reflow (ANR) were determined with both MCE in vivo and pathological examination after the swine were killed. RESULTS: The platelet aggregation rates (MAR) after AMI were 46.8% and 45.7% respectively in tirofiban group and A-C Combination group, and significantly decreased to 12.9% and 14.3% respectively after the administration of drugs (both P < 0.01) with equivalent potency (P > 0.05). The left ventricular function was significantly improved in tirofiban group in comparison with control group (P < 0.05 - 0.01), the coronary blood flow volume (CBV) 1 h after reperfusion was 73.2% in tirofiban group, significantly higher than that of control group (45.8%, P < 0.01), and the ANR of tirofiban group was 22.8% and 23.2% judged by MCE and pathological examination respectively, both significantly smaller than those of control group (78.5% and 82.3%, both P < 0.01), and the NA of tirofiban group was 89.2%, significantly smaller than that of Control Group (98.5%, P < 0.05). However, there were not significant differences in left ventricular function, central blood volume, ANR and NA between A-C combination group and control group (all P > 0.05). CONCLUSION: Tirofiban is markedly effective in attenuating myocardial no-reflow after reperfusion; in contrast, A-C combination is totally ineffective.

[Beneficial effects of Tong-xin-luo (herb) on myocardial no-reflow after acute myocardial infarction and reperfusion: experiment of mini-swine model].

OBJECTIVE: To evaluate the beneficial effects of Tong-xin-luo on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion. METHODS: Forty mini-swine were randomized into 5 equal groups: control group, low-dose group (pretreated with Tong-xin-luo 0.05 g.kg(-1).d(-1) for 3 days), medium-dose group (pretreated with Tong-xin-luo 0.2 g .kg(-1).d(-1) for 3 days), high-dose group (pretreated with Tong-xin-luo 0.5 g.kg(-1).d(-1) for 3 days), and sham-operation group. The swine in the former four groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion. Left ventricle systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP), rate of maximum pressure change in left ventricle (+/- dp/dt(max)), cardiac output (CO), and heart rate (HR) were measured 5 min before AMI in all groups and 180 min after AMI and 60 min after reperfusion in the groups 1-4. Coronary blood volume (CBV) was recorded 5 min before AMI in all groups and immediately and 60 min after reperfusion in the group 1-4. Myocardial contrast echography (MCE) was used before AMI, 3 h after AMI, and 60 min after reperfusion in the group 1-4 so as to calculate the left ventricle wall area (LVWA), ligation area (LS), and %LA. Sixty minutes after reperfusion thioflavin-S was injected into the left ventricle to dye the reperfusion area, then the descending anterior branch was re-ligated at the original site and Evan's blue was injected into the left ventricle to dye the area outside the reperfusion area blue. The heart was taken out immediately to undergo pathological examination and calculation of LVWA, LS, area of no-reflow (SNR), LA, ANR. necrosis area (NS), and NA. RESULTS: (1) In the control group, systolic and diastolic blood pressures (SBP and DBP), LVSP, +/- dp/dt(max), and CO significantly decreased (P < 0.05 or P < 0.01), while LVEDP significantly increased (P < 0.01) 3 hour after AMI, and then LVSP was significantly recovered while +/- dp/dt(max) further significantly decreased (both P < 0.05) 60 minutes after reperfusion. In the 3 Tongxinluo groups, the changes of LVSP, +/- dp/dt(max), CO and LVEDP were the same as those in the control group 3 hours after AMI, and 60 minutes after reperfusion, +/- dp/dt(max), CO and LVEDP were recovered significantly in the high-dose group to degrees better than those in the control group (all P < 0.05). (2) In the control group, the LS values measured by MCE in vivo and by pathological evaluation were similar (P > 0.05), and the SNR was 78.5% by MCE in vivo and was 82.3% by pathological evaluation with the final NS reaching 98.5% of LS. There was no significant difference in LS by both MCE and pathological evaluation between the Tongxinluo groups and control group, though the values of SNR by both methods in the medium and high-dose groups were 41.1% and 42.4% and 24.1% and 25.0% respectively, all significantly lower than those in the control group and low-dose group (P < 0.05 or P < 0.01) with the values in the high-dose group being significantly lower than those in the median-dose group (P < 0.05 and P < 0.01). The final NS of pathological evaluation was also significantly decreased to 90.2%and 81.2% of LS (P < 0.05). In the control group, CBV was significantly decreased to 45.8% and 50.6% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.01). In the high-dose group, CBV was also significantly decreased to 76% and 73.5% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.05), however, both significantly higher than those in the control group (both P < 0.01). CONCLUSION: Tongxinluo is effective in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area during AMI and reperfusion.

[Beneficial effects of diltiazem on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion].

OBJECTIVE: To evaluate the beneficial effects of diltiazem on myocardial no-reflow. METHODS: Twenty-four mini-swine were randomized into 3 equal groups: diltiazem-treated group subjected to 3 hours of coronary occlusion to cause acute myocardial infarction (AMI), followed by 60 minutes of reperfusion and injected with diltiazem into the coronary artery 1 minute before reperfusion, control group undergoing coronary occlusion followed by 60 minutes of reperfusion and injected with normal saline, and sham operation group. 5 minutes before AMI in all groups and 180 minutes after AMI and 60 minutes after re-perfusion in the diltiazem and control groups, hemodynamic data, such as heart rate (HR), left ventricular systolic pressure (LVSP). Left ventricular end diastolic pressure (LVEDP), +/- dp/dt(max), cardiac output (CO), and coronary blood volume (CBV) were measured. Myocardial contrast echography (MCE) was used to measure the left ventricle wall area (LVWA) and ligation area (LA) so as to calculate LA and to measure the area of no-reflow (ANR) so as to calculate ANR. 60 minutes after reperfusion thioflavin-S was injected into left ventricle so as to color the reperfused area and then the descending anterior branch was re-ligated and Evan's blue was injected into the left ventricle to color the area outside the ligation area. The heart was taken out to undergo histological examination. RESULTS: (1) In comparison with the values before AMI the LVSP, +/- dp/dt(max), and CO of the control group significantly declined (P < 0.05, 0.01), while the LVEDP significantly increased (P < 0.01) by the end of 3 hours after LAD occlusion; and the LVSP significantly increased and the +/- dp/dt(max) further significantly declined (both P < 0.05) 60 minutes after reperfusion. In the diltiazem group, the changes of LVSP, +/- dp/dt(max), CO, and LVEDP were the same as those in the control group after 3 hours of AMI, while the +/- dp/dt(max), CO, and LVEDP recovered significantly, more significantly than those in the control group, 60 minutes after reperfusion (all P < 0.05). (2) In the control group, the sizes of coronary ligation area (LA) measured by both MCE in vivo and histopathological evaluation were similar (P > 0.05), and the values of area of no-reflow (ANR) measured by MCE in vivo and histopathological evaluation were 78.5% and 82.3% respectively with the final necrosis area (NA) reaching 99% of the LA. There was no significant difference in LA measured by both MCE and histopathological evaluation between the control and diltiazem groups, while the values of ANR measured by both methods was significantly decreased to 19.9% and 20.6% that before AMI respectively in the diltiazem group (both P < 0.01). There was no significant difference in NA between the control and diltiazem groups (P > 0.05). The CBV of the control group was significantly declined to 45.8% and 50.6% of the baseline value respectively immediately and 60 minutes after reperfusion (both P < 0.01), while the CBV of the diltiazem group became 80.4% and 79.3% of the baseline value respectively immediately and 60 minutes after reperfusion (both P < 0.05), both significantly higher than those of the control group (both P < 0.01). CONCLUSION: Diltiazem is effective both in preventing myocardial no-reflow and improving left ventricular function, but not in reducing MI size during AMI and reperfusion.

[Comparison of doxycycline, losartan, and their combination on the expression of matrix metalloproteinase, tissue inhibitor of matrix metalloproteinase, and collagen remodeling in the noninfarcted myocardium after acute myocardial infarction in rats].

OBJECTIVE: To compare the effects of matrix metalloproteinase (MMP) inhibitor doxycycline, losartan, and their combination on the expression of MMP-8, 13, tissue inhibitor of MMP-1, 2 (TIMP-1, 2), and collagen remodeling in the noninfarcted myocardium after acute myocardial infarction (AMI) in rats. METHODS: Two hundred and fifty-four AMI rats, induced by left coronary ligation, were randomly assigned to the following groups: (1) AMI controls group (n = 64); (2) doxycycline group (30 mg x kg(-1) x d(-1), n = 63); (3) losartan group (10 mg x kg(-1) x d(-1), n = 62); (4) concomitant doxycycline and losartan group (30 and 10 mg x kg(-1) x d(-1) respectively, n = 65); and (5) Sham-operated rats (n = 30), which were randomly selected to serve as noninfarction controls. Each group was further divided into three subgroups of 1, 2, and 4 weeks that received treatment. After the completion of treatment, the rats were killed. The mRNA and protein expression of MMPs and TIMPs in the noninfarcted myocardium were quantified by RT-PCR and Western blot, respectively. The type I and type III collagen volume fraction (CVF) of the noninfarced myocardium were assessed immunohistochemically. RESULTS: No significant difference existed in myocardial infarction sizes among the 12 subgroups of AMI controls and the three treatment groups (42%-48%, all P > 0.05). Compared with sham operated rats, the mRNA and protein expression of MMP-8 and 13 significantly increased by 39%-183% in all three subgroups of AMI controls (all P < 0.05), except both of their mRNA expressions in 2-week subgroups; the mRNA and protein levels of TIMP-1 increased only in 1-week subgroup of AMI controls by 104% and 67%, respectively (both P < 0.05); the mRNA of TIMP-2 increased in all 1, 2, and 4-week subgroups by 144%-232% (all P < 0.05), but its protein expression lagged and only enhanced in 2 and 4-week subgroups of AMI controls by 231% and 332%, respectively (both P < 0.05). Meanwhile, both type I and type III CVF of noninfarcted myocardium significantly increased in all three subgroups of AMI controls (type I CVF: 3.01%-5.64% vs 1.53%-1.67%, P < 0.01-0.001; type III CVF: 2.19%-4.42% vs 1.46%-1.59%, P < 0.05-0.001), with type I CVF being higher in 4-week than in 1 and 2-week subgroups (5.64% vs 3.01% and 3.02% respectively, all P < 0.05). Compared with AMI controls, all three kinds of treatment significantly reduced the increased mRNA and protein expressions of MMP-8, 13 and TIMP-1, 2 after AMI by 14%-60% (all P < 0.05), as well as type I/III CVF in their 2 and 4-week subgroups (type I CVF: 1.56%-2.38% vs 3.02%-5.64%, P < 0.05-0.001; type III CVF: 1.92%-2.65% vs 4.19%-4.42%, P < 0.05-0.01), except for doxycycline's effect on type III CVF in any of its three subgroups (all P > 0.05). Among the three treatment groups, significant differences existed in the above mentioned indicators only at some subgroup levels (all P < 0.05). CONCLUSIONS: Like losartan, doxycycline can also suppress the enhanced mRNA and protein expression of MMP-8, 13 and TIMP-1, 2, and reduce type I collagen deposition in the noninfarcted myocardium after AMI in rats. However, it has no effect on type III collagen deposition.

[Comparison of doxycycline, losartan, and their combination in the prevention of post-infarction remodeling in rats].

OBJECTIVE: To compare the effects of doxycycline, losartan, and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats. METHODS: Twenty-four hours after the induction of AMI, the 254 survival rats were randomly assigned to the following groups and received drug treatment: (1) AMI controls (n=64), (2) doxycycline (30 mg x kg(-1) x d(-1), n = 63), (3) losartan (10 mg x kg(-1) x d(-1), n = 62), and (4) combination doxycycline and losartan (30 and 10 mg x kg(-1) x d(-1) respectively, n = 65) treatment groups. Also, sham operated rats (n = 30) were selected randomly. Each group was further divided into three subgroups of 1, 2, and 4 weeks of treatment. After the completion of treatment, hemodynamic studies were performed. Then, the heart of rat was fixed and analyzed pathologically. RESULTS: Exclusive of the dead rats and the hearts with the myocardial infarction size < 35% or > 50%, complete experimental data were obtained in 157 rats. Besides sham operated rats, there was no significant difference in myocardial infarction sizes among the 12 subgroups of AMI control and drug treatment groups (P> 0.05). Compared with sham operated rats, left ventricular end diastolic pressure (LVEDP) and left ventricular absolute weight and relative weight (LVAW and LVRW) were significantly increased in 1, 2, and 4 week subgroups of AMI controls (P < 0.05, P < 0.01, and P < 0.001, respectively), with LVEDP elevated more significantly in 4 week than in 1 and 2 week subgroups (P < 0.01); whereas the maximum rising and dropping rate of left ventricular pressure (+/-dp/dt) and its corrected value by left ventricular systolic pressure (+/-dp/dt/LVSP) were all significantly decreased only at 4 week subgroup of AMI controls (P < 0.001). Compared with AMI controls group, LVEDP was significantly decreased in all 1, 2, and 4 week subgroups of the three treatment groups (P < 0.05, P < 0.01, and P < 0.001, respectively); LVAW and LVRW were significantly decreased in 2 and 4 week subgroups of losartan and combination groups (P < 0.05, P < 0.01, P < 0.001, respectively), and in only 4 week subgroup in doxycycline (P < 0.05, P < 0.01, and P < 0.001, respectively); whereas the maximum dropping rate of left ventricular pressure and the corrected value of left ventricular pressure rising and dropping rate were significantly increased only in 4 week subgroups of all three treatment groups (P < 0.05, P < 0.01, respectively). There is no significant difference in all indices above among the three treatment groups at all three time points (P > 0.05). CONCLUSION: It is indicated that doxycycline can prevent left ventricular remodeling and improve its systolic and diastolic function after AMI in rats, with the equivalent effect to that of losartan. There seems no additive effect when the two drugs are used in combination.