Aged ; Angioplasty, Balloon, Coronary ; instrumentation ; methods ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; pathology ; therapy

The study aimed to evaluate the therapeutic effect of nilotinib-loaded biocompatible gelatin methacryloyl (GelMA) microneedles patch on cardiac dysfunction after myocardial infarction(MI), and provide a new clinical perspective of myocardial fibrosis therapies. The GelMA microneedles patches were attached to the epicardial surface of the infarct and peri-infarct zone in order to deliver the anti-fibrosis drug nilotinib on the 10th day after MI, when the scar had matured. Cardiac function and left ventricular remodeling were assessed by such as echocardiography, BNP (brain natriuretic peptide) and the heart weight/body weight ratio (HW/BW). Myocardial hypertrophy and fibrosis were examined by WGA (wheat germ agglutinin) staining, HE (hematoxylin-eosin staining) staining and Sirius Red staining. The results showed that the nilotinib-loaded microneedles patch could effectively attenuate fibrosis expansion in the peri-infarct zone and myocardial hypertrophy, prevent adverse ventricular remodeling and finally improve cardiac function. This treatment strategy is a beneficial attempt to correct the cardiac dysfunction after myocardial infarction, which is expected to become a new strategy to correct the cardiac dysfunction after MI. This is of great clinical significance for improving the long-term prognosis of MI patients.
Humans ; Myocardial Infarction/drug therapy* ; Cardiomegaly ; Natriuretic Peptide, Brain/therapeutic use* ; Fibrosis ; Myocardium/pathology*

BACKGROUNDIn cardiology, it is controversial whether different therapy strategies influence prognosis after acute coronary syndrome. We examined and compared the long-term outcomes of invasive and conservative strategies in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and characterized the patients selected for an invasive approach.

METHODSA total of 976 patients with acute NSTEMI were collected from December 2006 to October 2012 in the First Affiliated Hospital of Dalian Medical University Hospital. They are divided into conservative strategy (586 patients) and invasive strategy (390 patients) group. Unified follow-up questionnaire was performed by telephone contact (cut-off date was November, 2013). The long-term clinical events were analyzed and related to the different treatment strategies.

RESULTSThe median follow-up time was 29 months. Mortality was 28.7% (n = 168) in the conservative group and 2.1% (n = 8) in the invasive management at long-term clinical follow-up. The secondary endpoint (the composite endpoint) was 59.0% (n = 346) in the conservative group and 30.3% (n = 118) in the invasive management. Multivariate analysis showed that patients in the conservative group had higher all-cause mortality rates than those who had the invasive management (adjusted risk ratio [RR] = 7.795; 95% confidence interval [CI]: 3.796-16.006, P < 0.001), and the similar result was also seen in the secondary endpoint (adjusted RR = 2.102; 95% CI: 1.694-2.610, P < 0.001). In the subgroup analysis according to each Thrombolysis in Myocardial Infarction risk score (TRS), log-rank analysis showed lower mortality and secondary endpoint rates in the invasive group with the intermediate and high-risk patients (TRS 3-7).

CONCLUSIONSAn invasive strategy could improve long-term outcomes for NSTEMI patients, especially for intermediate and high-risk ones (TRS 3-7).

Acute Coronary Syndrome ; mortality ; pathology ; therapy ; Aged ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; mortality ; pathology ; therapy ; Prognosis ; Retrospective Studies

OBJECTIVETo compare the acute myocardial infarction models in Beagle dogs and mongrel dogs, and study whether the Beagle dog model is sensitive to drug intervention.

METHODThe acute myocardial infarction model of dog was set up through ligation of anterior descending branch of coronary artery in dogs, in order to observe morphological changes of the heart and determine artery length and heart coefficient of exposed anterior descending branch of coronary artery. The epicardium electrocardiogram (sigmaST, N-ST) was used to measure the degree of myocardial ischemia. The quantitative histological assay (nitroblue tetrazolium, N-BT stain) was adopted to determine the area of myocardial infarction.

RESULTThere was no significant difference between Beagle dogs and mongrel dogs in terms of sigmaST, N-ST and ischemia area. The diltiazem group of Beagle dogs showed obvious reduction in the ischemia area (P < 0.05 and P < 0.01), with notable decline in sigmaST and N-ST, however, it had no statistical difference compared with the Beagle dog model group. Beagle dogs had clear coronary branches, longer exposed arteries and less difference in organ coefficient, which were suitable for the preparation of the myocardial infarction model, whereas mongrel dogs had irregular coronary branches and exposed arteries, with greater individual difference.

CONCLUSIONBeagle dogs are superior to mongrel dogs in the preparation of the acute myocardial infarction model, which is sensitive to for drug intervention.

Acute Disease ; Animals ; Disease Models, Animal ; Dogs ; Electrocardiography ; Female ; Male ; Myocardial Infarction ; drug therapy ; pathology ; Myocardium ; pathology

Objective To quantitatively evaluate the associations of infarct size, regional myocardial function examined by cardiac magnetic resonance feature tracking (CMR-FT) strain analysis with infarct location in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention.Methods Cardiac magnetic resonance images were retrospectively analyzed in 95 consecutive STEMI patients with successful reperfusion. The patients were divided into the anterior wall myocardial infarction (AWMI) and nonanterior wall myocardial infarction (NAWMI) groups. Infarct characteristics were assessed by late gadolinium enhancement. Global and regional strains and associated strain rates in the radial, circumferential and longitudinal directions were assessed by CMR-FT based on standard cine images. The associations of infarct size, regional myocardial function examined by CMR-FT strain analysis with infarct location in STEMI patients were evaluated by the Spearman or Pearsonmethod. Results There were 44 patients in the AWMI group and 51 in the NAWMI group. The extent of left ventricular enhanced mass was significantly larger in patients with AWMI compared with the NAWMI group (24.47±11.89, 21.06±12.08 %LV; t=3.928, P = 0.008). In infarct zone analysis, strains in the radial, circumferential and longitudinal directions were remarkably declined in the AWMI group compared with the NAWMI group (z=-20.873, -20.918, -10.357, all P < 0.001). The volume (end-systolic volume index), total enhanced mass and extent of enhanced mass of the left ventricular were correlated best with infarct zone strain in the AWMI group (all P < 0.001). Conclusion In STEMI patients treated by percutaneous coronary intervention, myocardial damage is more extensive and regional myocardial function in the infarct zone is lower in the AWMI group compared with the NAWMI group.
Humans ; Anterior Wall Myocardial Infarction/therapy* ; ST Elevation Myocardial Infarction/pathology* ; Contrast Media ; Retrospective Studies ; Ventricular Function, Left ; Magnetic Resonance Imaging, Cine/methods* ; Gadolinium ; Magnetic Resonance Imaging ; Myocardial Infarction/diagnostic imaging* ; Magnetic Resonance Spectroscopy ; Percutaneous Coronary Intervention ; Stroke Volume

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 study the effect of different access routes on autologous satellite cell implantation to stimulate myocardial regeneration.

METHODSSatellite cells were procured from skeletal muscle (gluteus max) of adult mongrel canine, cultured, proliferated and labeled with 4', 6-diamidino-2-phenylindone (DAPI) in vitro. The cells were autologously implanted into the site of acute myocardial infarction by local injection or perfusion through the ligated distal left anterior descending coronary artery. Specimens were harvested 2, 4 and 8 weeks later for histological study.

RESULTSThe labeling efficiency of satellite cells with DAPI was close to 100%. Fluorescent cells were found at the infarcted zone, papillary muscle and local injection site. Some of these cells had progressively differentiated into striated muscle fibers connected to intercalated discs. The infant cells appeared different from the mature myocardium under an electron microscope. Satellite cells implanted by perfusion through the coronary artery were arranged in order of consistency with host myocardial fibers. The satellite cells, implanted by local injection, were found growing in a disordered way.

CONCLUSIONSatellite cells, implanted by coronary artery perfusion, can progressively differentiate into striated muscle fibers, arranging in order and disseminating over the infarcted zone. This approach seems more favorable for the recovery of myocardial contractile function than that of local injection.

Animals ; Cell Differentiation ; physiology ; Dogs ; Myocardial Infarction ; pathology ; therapy ; Myocardium ; cytology ; Regeneration ; Satellite Cells, Skeletal Muscle ; cytology ; transplantation ; Transplantation, Autologous

BACKGROUNDA growing volume of data suggests that simple manual thrombus aspiration followed by direct stenting improves myocardial reperfusion and clinical outcome compared with conventional primary PCI, but there is still limited data comparing the in vivo performance among different devices. This study aimed to compare the efficacy and operability of thrombus aspiration by the Diver CE (Invatec, Brescia, Italy) and ZEEK (Zeon Medical Inc., Tokyo, Japan) aspiration catheters in ST-segment elevation myocardial infarction (STEMI) and their impact on 3-month outcome.

METHODSFrom September 2004 to June 2008, 298 consecutive patients with STEMI who received manual thrombus aspiration were involved in a single center retrospective analysis. Of them, 229 and 69 were treated with Diver CE and ZEEK aspiration catheters, respectively. Primary endpoints were myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade, ST-segment elevation resolution (STR), device pushability and trackability as judged by the frequency of usage of dual guide wires and aspiration efficacy as indicated by size distribution of aspirated thrombi. Secondary endpoints were 3-month outcome including left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), as well as cardiac death, target lesion revascularization (TLR), re-infarction and their combination as major adverse cardiac events (MACE).

RESULTSBaseline characteristics were not different between the two groups expect for a higher frequency of temporary cardiac pacing in the ZEEK group (ZEEK) than in the Diver CE group (Diver CE) (0.44% vs 5.8%, P = 0.002). Visible retrieved thrombi were achieved in 65.9% of the Diver CE and 68.1% of the ZEEK (P = 0.74). Aspirated thrombi were categorized as small thrombi (< 3.5 mm), moderate thrombi (3.5-7.0 mm) and large thrombi (> 7.0 mm). Small thrombi were more frequently seen in the Diver CE (61.6% vs 42.6%), whereas moderate and larger thrombi were more frequently found in the ZEEK (38.4% vs 57.4%) (P = 0.021). Rates of dual wire utilization were 1.7% of the Diver CE and 7.2% of the ZEEK (P = 0.052). There were no differences in MBG, STR and TIMI flow grade between the two groups. No differences were found in cardiac death, TLR, re-infarction, MACE, LVEDD and LVEF between the Diver CE and the ZEEK during 3-month follow-up.

CONCLUSIONSBoth Diver CE and ZEEK manual aspiration catheters are effective for thrombectomy in STEMI. In clinical practice, ZEEK presents a stronger aspiration capacity for moderate to large thrombi compared with Diver CE, but Diver CE displays a trend towards better pushability and trackability than ZEEK. Differences in aspiration capacity and operability between Diver CE and ZEEK in this setting do not influence myocardial reperfusion and 3-month outcome.

Coronary Angiography ; Echocardiography ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; pathology ; surgery ; Thrombectomy ; instrumentation ; methods ; Treatment Outcome

OBJECTIVETo evaluate the possibility that using intracoronary delivery of autologus bone marrow-derived mesenchymal stem cells (MSCs) to improve the cardiac function after acute myocardial infarction (AMI) in miniature pig.

METHODSMSCs were cultured in Dulbecco's modified Eagle's medium-F12 (DMEM/F12) medium. AMI model was made by blocking the blood stream of the first diagonal branch in miniature pig, and released the branch after 90 minutes. After 10-14 days, (4-6) x 10(7) culture-expanded autologus 4', 6-diamidino-2-phenylindole (DAPI)-labelled MSCs were transplanted into each host heart's AMI area through intracoronary way. Ultrasonic cardiography (UCG) was performed to observe the left ventricular function at 3 months after transplantation. The cellular transplanted hearts were harvested and investigated by immunohistochemical analysis.

RESULTSLeft ventricular function of the MSCs group was improved significantly 3 months later compared with the control group [(54.65 +/- 3.39) vs (43.98 +/- 4.21)%, (P < 0.01)]. Exogenous MSCs survived and site-differentiated into cardiomyocytes in infracted hearts.

CONCLUSIONMSCs can play a benificial role to repair damaged heart. Heart function can be improved after MSCs transplantation in porcine myocardial infarction model.

Animals ; Female ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Myocardial Infarction ; pathology ; physiopathology ; therapy ; Swine ; Swine, Miniature ; Transplantation, Autologous ; Treatment Outcome

The purpose of this study was to observe whether human peripheral dervied monouncleas cells (hMNCs) could participate in the regeneration process of the ischemic hearts in the way of differentiating into cardiomyocytes, vascular endothelial cells and smooth muscle cells. hMNCs were transplanted into the bodies of the mice with myocardial infarction through the tail vein injection. Hearts were harvested 2-12 weeks after injection then sliced up into frozen sections of 5 micron thickness. Double immunofluorescence staining was used to test the differentiation of the grafted cells into cardiomyocytes, smooth muscle cells and vascular endothelial cells which revealed that cells expressing both HLA and TNT, HLA and alpha-SMA, HLA and vWF existed in the hearts of the mice. According to the study, it is probable that hMNCs could participate in the regeneration process of the infarcted hearts in the way of differentiation.
Animals ; Cell Differentiation ; physiology ; Humans ; Leukocytes, Mononuclear ; transplantation ; Mice ; Mice, Nude ; Myocardial Infarction ; pathology ; therapy ; Myocytes, Cardiac ; cytology ; Transplantation, Heterologous