OBJECTIVEThis study was designed to investigate the relationship between high sensitivity C-reactive protein (hs-CRP) level at admission and myocardial perfusion after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction.

METHODSThe study population consisted of 197 patients (154 men, mean age 60.94 +/- 11.62 years) who were admitted to our hospital with first acute myocardial infarction and underwent primary PCI in the infarct-related artery. Myocardial perfusion was evaluated by Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG). Patients were divided into two groups according to TMPG after PCI. Group 1 consisted of 39 patients with TMPG 0 - 1 and group 2 consisted of 158 patients with TMPG 2 - 3. Serum hs-CRP levels at admission were measured.

RESULTShs-CRP level at admission was significantly higher in group 1 than that in group 2 (P = 0.026).

CONCLUSIONSHigher hs-CRP level at admission in patients with acute myocardial infarction is related to poorer myocardial perfusion post primary PCI.

Aged ; Angioplasty, Balloon, Coronary ; C-Reactive Protein ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; therapy ; Myocardial Reperfusion

OBJECTIVETo assess the effect of Tongxinluo on cytokines and myocardial no-reflow in early reperfusion of acute myocardial infarction (AMI).

METHODSForty mini-swine were divided into five groups randomly, sham group, control group, low dose (0.1 g/kg), medium dose (0.2 g/kg) and high dose (0. 4 g/kg) group of Tongxinluo (which were administered 2 h before reperfusion), eight swine in each group. Animals except those in the sham group were subjected to 1.5 h of coronary occlusion followed by 3 h of reperfusion. Serum contents of P-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), interleukin 6 (IL-6) and interleukin 10 (IL-10), as well as myocardial contrast echocardiography (MCE) were evaluated at baseline, and after 1.5 h of AMI and 3 h of reperfusion.

RESULTS(1) Compared with that of the control group, high dose of Tongxinluo could reduce serum contents of P-selectin and ICAM-1 at 1.5 h of AMI (all P<0.05), and P-selectin, ICAM-1, VCAM-1, and IL-6 at 3 h of reperfusion significantly (all P< 0.05), accompanied by significantly elevated IL-10 (P<0.05). (2) Compared with that of control group, high dose of Tongxinluo could reduce no-reflow area at 3 h of reperfusion significantly [(6.59 +/- 1.73) cm2 vs (4.68 +/- 1.53) cm2, P<0.05].

CONCLUSIONHigh dose of Tongxinluo could effectively reduce serum contents of adhesion and pro-inflammatory cytokines, regulate anti-inflammatory factor levels, and attenuate no-reflow area in the early reperfusion of AMI. It thus provided experimental basis for its clinical application.

Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Intercellular Adhesion Molecule-1 ; metabolism ; Myocardial Infarction ; drug therapy ; metabolism ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; drug therapy ; metabolism ; Myocardium ; metabolism ; P-Selectin ; metabolism ; Phytotherapy ; Swine ; Swine, Miniature

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

This study evaluated the effects of early treatment with β-adrenergic blocker metoprolol on ventricular remodeling and function after acute myocardial infarction (AMI) by using high frequency ultrasound. The relationship between the efficacy and the expression level of cardiac myocardial inflammatory cytokine was examined in rats. The rat model of AMI was induced by ligating the left anterior descending artery. The surviving rats were randomly assigned to two experimental groups: MI control (MI) group and MI metoprolol (MI-B) group, with the rats undergoing sham operation serving as normal control (Sham). MI-B group was given metoprolol for 4 weeks (refer to the CCS-2 protocol) and the other two groups received equal volume of saline via intragastric (i.g.) administration. The ventricular remodeling and function were evaluated by high frequency ultrasound 4 weeks after the treatment. Then all rats were sacrificed for pathological examination and immunohistochemistrical detection of inflammatory cytokines, including IL-1β, IL-6, IL-10 and TNF-α. Compared with the MI group, the left ventricular end-systolic dimension, end-diastolic dimension, end-systolic volume and end-diastolic volume of the MI-B group were significantly decreased (P<0.01), while the left ventricular anterior wall end-diastolic thickness, ejection fraction and fractional shortening were obviously increased (P<0.01). The conspicuous improvement in the left ventricular morphology and function was coincident with the markedly reduced TNF-α and IL-1β expression and the increased IL-10 expression. We are led to conclude that early metoprolol treatment for AMI can regulate myocardial inflammatory cytokine expression to improve cardiac function and the underlying mechanism might be that it decreases the level of pro-inflammatory cytokines and increases the level of its anti-inflammatory counterparts in cardiac myocytes. Our study also showed that echocardiography is a useful technique for the structural and functional assessment of left ventricle after acute myocardial infarction.
Animals ; Cytokines ; metabolism ; Inflammation ; drug therapy ; metabolism ; Male ; Metoprolol ; pharmacology ; Myocardial Infarction ; drug therapy ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Ultrasonography ; methods

Electrocardiography ; Female ; Fetal Hypoxia ; complications ; Humans ; Infant, Newborn ; Myocardial Infarction ; etiology ; therapy ; Myocardium ; metabolism ; pathology ; Treatment Outcome

BACKGROUNDMyocardial tissue-level perfusion failure is associated with adverse outcomes following ST-elevation myocardial infarction (STEMI) despite successful epicardial recanalization. We have developed a new quantitative index-thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC)--for assessing myocardial tissue level perfusion. However, factors affecting this novel index of myocardial perfusion are currently unknown.

METHODSA total of 255 consecutive STEMI patients undergoing primary angioplasty were enrolled. Myocardial tissue level perfusion was assessed by TMPFC, which measures the filling and clearance of contrast in the myocardium using cine-angiographic frame counting. We differentiate three groups with two cut off values for TMPFC: a TMPFC of 90 frames was the upper boundary of the 95% confidence interval (CI) for the TMPFC observed in normal arteries, and a TMPFC of 130 was the 75th percentile of TMPFC.

RESULTSSTEMI patients with TMPFC > 130 frames (68 patients, 26.7%) had higher clinical and angiographic risk factor profiles as well as a higher 30-day MACE rate compared with those with TMPFC ≤ 90 frames and those with TMPFC > 90 and ≤ 130 frames. Multivariable analysis identified that the independent predictors of TMPFC > 130 frames were age ≥ 75 years (OR 2.08, 95%CI 1.21 to 3.58, P = 0.007), diabetes (OR 1.37, 95%CI 1.01 to 1.86, P = 0.042), Killip class ≥ 2 (OR 1.52, 95%CI 1.05 to 2.21, P = 0.027), and prolonged pain-to-balloon time (OR 1.73, 95%CI 1.07 to 2.79, P = 0.013). TMPFC > 130 frames was identified as the strongest independent predictor of 30-day major adverse cardiac event (MACE) (OR 2.77, 95%CI 1.21 to 6.31, P = 0.008), along with age ≥ 75 years (OR 2.19, 95%CI 1.11 to 4.33, P = 0.016), female gender (OR 1.67, 95%CI 1.03 to 2.70, P = 0.038), and Killip class ≥ 2 (OR 1.83, 95%CI 1.07 to 3.14, P = 0.021).

CONCLUSIONSSTEMI patients with poor myocardial perfusion assessed by TMPFC had higher risk factor profiles. Advanced age, diabetes, higher Killip class, and longer ischemia time were independent predictors of impaired TMPFC after primary percutaneous coronary intervention. These results emphasize that particular attention should be paid on myocardial microvascular reperfusion in STEMI patients with these risk factors.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; pathology ; therapy ; Myocardial Reperfusion ; Myocardium ; metabolism ; pathology

OBJECTIVETo 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.

METHODSTwenty-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.

RESULTSIn 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).

CONCLUSIONThe endothelium injury may be one of the important mechanisms for no-reflow phenomenon. Adenosine cay prevent endothelium from injury to reduce no-reflow.

Adenosine ; pharmacology ; therapeutic use ; Animals ; Disease Models, Animal ; Endothelin-1 ; genetics ; metabolism ; Female ; Male ; Myocardial Infarction ; drug therapy ; physiopathology ; Myocardial Reperfusion ; Swine ; Swine, Miniature

OBJECTIVETo study the protection effects and the mechanisms of Huoxue Anxin Recipe (HAR) on acute myocardial infarction (AMI) rats.

METHODSThe AMI Wistar rat model was prepared by ligating the left anterior descending coronary artery. By taking elantan long as the positive control drug, HAR was extracted from Chinese herbs by modern pharmacological methods and composed according to theories of Chinese medicine (CM). The medication time started from the day of modeling to the 21st day of the modeling. The heart function, the morphological changes of the heart, changes in the mRNA and protein levels of toll like receptor 4 nuclear factor kappa B tumor necrosis factor alpha (TLR4-NFkappaB-TNFalpha) pathway were observed.

RESULTSCompared with the sham-operation group, the ejection fraction (EF) and left ventricular fractional shortening (FS) significantly decreased (P < 0.01), the left ventricular intemal dimension end-diastolic (LVIDd) and left ventricular internal dimension end-systolic (LVIDs) significantly increased (P < 0.01), the mRNA and protein levels of TLR4-NFkappaB-TNFalpha channel significantly increased in the model group (P < 0.01). The infarction in the front wall of the left ventricle was obviously seen, accompanied with severe inflammatory cell infiltration and collagen deposition in model group. Compared with the model group, the EF and FS significantly increased, LVIDd and LVIDs significantly decreased in the positive control group, the high and low dose HAR groups (P < 0.05, P < 0.01). The infracted area of the front wall of the left ventricle was obviously contracted. The inflammatory cell infiltration and collagen deposition were obviously alleviated. In the high and low dose HAR groups, the mRNA and protein expression levels of TLR4-NFkappaB-TNFalpha significantly decreased (P < 0.05, P < 0.01), but no inhibition was found in the positive control group.

CONCLUSIONSHAR could significantly improve the morphological structures and functional abnormality induced by myocardial ischemia in AMI rats. Its effects was correlated with inhibiting TLR4-NFkappaB-TNFalpha pathway.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Myocardial Infarction ; drug therapy ; metabolism ; Myocardial Ischemia ; metabolism ; prevention & control ; NF-kappa B ; metabolism ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo detect the regulation of angiogenic genes involved in the processes of collateral development.

METHODSMyocardial infarction (MI) scar was induced by cryoinjury in New Zealand rabbits. Four weeks after MI, 24 hours before cell transplantation, bone marrow was aspirated from the right thigh bone and mononuclear bone marrow cells (BMCs) were isolated by Ficoll density gradient centrifugation. Then the mononuclear BMCs (n = 8) or IMDM culture medium (n = 8) were transplanted into infarction scar and the periphery. Four weeks after mononuclear BMCs transplantation, DNA microarray analysis was performed to detect the regulation of angiogenesis-related genes in infarction scar and the periphery. And the differences of angiogenic genes expression were compared among several important growth factors by Western blot.

RESULTSDNA microarray analysis showed the detail regulation of genes involved in the angiogenic processes. There were 15 genes upregulated over 3 times in the infarction scar. In addition, we also found more genes are involved in the process of angiogenesis in its periphery than in the infarction scar (40 genes vs. 15 genes). Western bolt analysis further demonstrated that mononuclear BMCs transplantation was capable of increasing the levels of VEGF, FGF and Angiopoietin-I expression in the infarction scar and its periphery, compared with the control group, P < 0.05.

CONCLUSIONThese findings indicate that the natural angiogenic processes leading to collateral development are extremely complex, since many kinds of bone marrow-derived growth factors involved in the processes after mononuclear BMCs transplantation into infarction sites.

Animals ; Bone Marrow Transplantation ; Female ; Gene Expression Profiling ; Male ; Monocytes ; metabolism ; Myocardial Infarction ; genetics ; pathology ; therapy ; Neovascularization, Pathologic ; metabolism ; Oligonucleotide Array Sequence Analysis ; Rabbits ; Up-Regulation ; Ventricular Remodeling

OBJECTIVE: To determine the improvements of post-infarction heart function after transplantation of autologous skeletal myoblasts transfected with VEGF165 in rabbits. METHODS: Myocardium infarction was induced in rabbits by left anterior descending coronary artery ligation. At 2 weeks, 1.75×10(7) autologous skeletal myoblasts transfected with pcDNA3.1-VEGF165 were infused into the region of MI via direct intramuscular injection; pcDNA3.1 served as a control. RESULTS: The DAPI-labeled and Desmin-positive immunostained skeletal myofibers were found throughout the infracted areas and border zones, and the density of blood capillary in the MI region transplanted by myoblasts with VEGF165 was increased (measured 4 weeks later and compared with controls). Heart function was examined by the Buxco system and demonstrated that maximum dp/dt [(1607.23±102.67) mmHg/s vs (1217.77±89.91) mmHg/s] and minimum dp/dt [(-1535.09 ± 81.34) mmHg/s vs (1174.58 ± 91.5) mmHg/s] were improved in the heart transplanted with the transfected myoblasts(P<0.05). CONCLUSION Autologous skeletal myoblasts transfected with VEGF165 could ameliorate the blood supply in the MI region, and aid recovery of heart function more quickly in post-infarction hearts. This suggests an effective treatment for myocardium infarction.
Animals ; Female ; Myoblasts, Skeletal ; metabolism ; transplantation ; Myocardial Infarction ; physiopathology ; therapy ; Rabbits ; Recovery of Function ; Transfection ; Transplantation, Autologous ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Ventricular Function, Left ; physiology