After Acute Myocardial Infarction Group Research Articles

Guanxin V alleviates ventricular remodeling after acute myocardial infarction with circadian disruption by regulating mitochondrial dynamics.

Circadian disruption has been a common issue due to modern lifestyles. Ventricular remodeling (VR) is a pivotal progressive pathologic change after acute myocardial infarction (AMI) andcircadian disruption may have anegative influence on VR according to thelatest research. Whether or notGuanxin V (GXV) has a positive effect on VR after AMI with circadian disruption drew our interest. Rats were randomly divided into asham group, anAMI group, anAMI with circadian disruption group, and anAMI with circadian disruption treated with the GXV group according to a random number table. RNA sequencing (RNA-Seq) was utilized to confirm the different expressed genes regulated by circadian disruption. Cardiac function, inflammation factors, pathological evaluation, and mitochondrial dynamics after the intervention were conducted to reveal the mechanism by which GXV regulated VR after AMI with circadian disruption. RNA-Seq demonstrated that NF-κB was up-regulated by circadian disruption in rats with AMI. Functional and pathological evaluation indicated that compared with the AMI group, circadian disruption was associcataed withdeteriorated cardiac function, expanded infarcted size, and exacerbated fibrosis and cardiomyocyte apoptosis. Further investigation demonstrated that mitochondrial dynamics imbalance was induced by circadian disruption. GXV intervention reversed the inflammatory status including down-regulation of NF-κB. Reserved cardiac function, limited infarct size, and ameliorated fibrosis and apoptosis were also observed in the GXV treated group. GXV maintained mitochondrial fission/fusion imbalance through suppressed expression of mitochondrial fission-associated proteins. The study findings suggestthat identified mitochondrial dysfunctions may underlie the link between circadian disruption and VR. GXV may exert cardioprotection after AMI with circadian disruption through regulating mitochondrial dynamics.

Study of the mechanism of Shexiang Baoxin pill-mediated angiogenesis in acute myocardial infarction.

The Shexiang Baoxin pill (SBP) is a commonly used drug for the treatment of coronary artery disease in China. More recently, some studies have found that it improved coronary microvascular function. This study aimed to explore the possible mechanism by which the SBP promotes angiogenesis after acute myocardial infarction (AMI). A rabbit model of acute myocardial infarction was established by ligating the left anterior descending coronary artery with silk thread, and the limb lead electrocardiogram was recorded to determine the success of the model. The rabbits were divided into a control group (SBP + normal rabbit group), a sham operation group, a saline + AMI group and an SBP + AMI group. There were 10 rabbits in each group. The animals were sacrificed and myocardial tissue was collected seven days after the operation. Haematoxylin-eosin staining was used to observe the histological changes in the rabbit myocardium in each group. The degree of acute myocardial infarction was observed with picric acid staining, which was used to detect the expression of vascular endothelial growth factor (VEGF), silent information regulator 1 (SIRT1), Beclin1 and mTOR protein in the myocardial tissue of each group. Immunofluorescence CD31-labelled microvascular density (MVD) was used to observe the vascular regeneration of the rabbits in each group. Compared with the normal saline + AMI group, the myocardial infarction area of the SBP + AMI group decreased and CD31 immunofluorescence-labelled MVD increased. Compared with the control and sham operation groups, the expression of VEGF, Beclin1 and mTOR in the normal saline + AMI group and the SBP + AMI group increased, while the expression of SIRT1 decreased. Compared with the normal saline + AMI group and the SBP + AMI group, the positive expression of VEGF, Beclin1, mTOR and SIRT1 in the SBP + AMI group was significantly increased. Autophagy was enhanced after acute myocardial infarction. SBP may affect angiogenesis through the SIRT1/mTOR signalling pathway after acute myocardial infarction to inhibit ventricular remodelling and a decline in cardiac function.

Effects and mechanism of renal denervation on ventricular arrhythmia after acute myocardial infarction in rats

BackgroundRenal denervation (RDN) can reduce ventricular arrhythmia after acute myocardial infarction (AMI), but the mechanism is not clear. The purpose of this study is to study its mechanism.MethodsThirty-two Sprague–Dawley rats were divided into four groups: control group, AMI group, RDN-1d + AMI group, RDN-2w + AMI group. The AMI model was established 1 day after RDN in the RDN-1d + AMI group and 2 weeks after RDN in the RDN-2w + AMI group. At the same time, 8 normal rats were subjected to AMI modelling (the AMI group). The control group consisted of 8 rats without RDN intervention or AMI modelling.ResultsThe study confirmed that RDN can reduce the occurrence of ventricular tachycardia in AMI rats, reduce renal sympathetic nerve discharge, and inhibit the activity of local sympathetic nerves and cell growth factor (NGF) protein expression in the heart after AMI. In addition, RDN decreased the expression of norepinephrine (NE) and glutamate in the hypothalamus,and NE in cerebrospinal fluid, and increased the expression level of γ aminobutyric acid (GABA) in the hypothalamus after AMI.ConclusionRDN can effectively reduce the occurrence of ventricular arrhythmia after AMI, and its main mechanism may be via the inhibition of central sympathetic nerve discharge.

Cardiac sympathetic afferent ablation to prevent ventricular arrhythmia complicating acute myocardial infarction by inhibiting activated astrocytes.

Enhanced cardiac sympathetic afferent reflex (CSAR) contributes to ventricular arrhythmia (VA) after acute myocardial infarction (AMI). However, central regulation mechanisms remain unknown. The aim of this study was to investigate whether local cardiac sympathetic afferent ablation (LCSAA) could reduce VA by inhibiting activated astrocytes in the hypothalamus paraventricular (PVN) in an AMI rat model. The rats were randomly divided into AMI, AMI + BD (baroreceptor denervation), AMI + LCSAA and AMI + BD+ LCSAA groups. Before the generation of AMI, BD and (or) LCSAA were performed. At 24 h after AMI, the incidence and duration of VA in AMI + LCSAA group and AMI + BD + LCSAA group were significantly reduced than AMI group (P < 0.05). Furthermore, LCSAA significantly reduced GFAP (a marker for activated astrocytes) positive cells and their projections as well as the level of TNF‐α and IL‐6 in the PVN of AMI + LCSAA group and AMI + BD+ LCSAA group, along with the decrease of neuronal activation in PVN and sympathetic nerve activity (P < 0.05). but BD had no obvious difference between AMI + LCSAA and AMI + BD + LCSAA group (P > 0.05). Therefore, LCSAA could decrease sympathoexcitation and VA occurrence in AMI rats by inhibiting astrocyte and neuronal activation in the PVN. Our study demonstrates that activated astrocytes may play an important role on CSAR in AMI.

Age-related difference in the impact of diabetes mellitus on all-cause mortality after acute myocardial infarction

AimTo test the hypothesis that the impact of diabetes mellitus on clinical outcomes after acute myocardial infarction (AMI) can vary by age. MethodsA total of 12,600 AMI patients from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) between November 2011 and December 2015 was classified into young (n = 3,590 [29%]) and old (n = 9,010 [72%]). Those less than 55 years of age were considered young. We performed comparisons of baseline characteristics, in-hospital treatments, and 3-year clinical outcomes between patients with and without diabetes after stratification according to age group. ResultsThe prevalence of diabetes mellitus was 27% in the young AMI group. In the multivariable adjusted model of the entire cohort, diabetes mellitus was associated strongly with 3-year all-cause mortality (13% vs. 6.8%; adjusted hazard ratio [HR], 1.318; 95% confidence interval [CI], 1.138–1.526; P<0.001). When the entire cohort was subdivided into two age groups, young diabetic patients showed a 107% higher mortality rate than those without diabetes (adjusted HR, 2.07 [1.15–3.72];P = 0.015). Meanwhile, old diabetic patients had a 25% higher risk of mortality than non-diabetic patients (adjusted HR, 1.25 [1.08–1.46];P = 0.004). The interaction of diabetes with age was significant (adjusted P for interaction = 0.008). ConclusionsDiabetes mellitus is not uncommon in younger AMI patients, and the relative risk of 3-year mortality is significantly higher in young patients than in older counterparts. More aggressive treatments are needed to prevent future cardiovascular events in younger patients after AMI.

Elevated Plasma Thymic Stromal Lymphopoietin After Acute Myocardial Infarction.

BackgroundThymic stromal lymphopoietin (TSLP), a distant paralog of the cytokine IL-7, has been shown to be associated with atherosclerosis. However, the effect of plasma TSLP level after acute myocardial infarction (AMI) remains largely unclear. Thus, we aimed to assess the relationship between the concentration of TSLP at admission and the risk of major adverse cardiovascular events (MACE) in AMI patients.MethodsA total of 175 patients with AMI and 145 unstable angina (UA) controls were recruited in the present study. The clinical characteristics were collected, and MACE was recorded during hospitalization and the follow-up period after discharge.ResultsThe median value (25, 75 percentiles) of TSLP concentrations in the AMI group was higher than that in the UA group [11.18 (8.14–15.22) vs. 8.56 (5.26–11.94) pg/ml, p < 0.001, respectively]. Multivariate linear regression analysis revealed that Troponin-I (standardized β = 0.183, p = 0.004) was an independent factor for TSLP. According to the median of TSLP concentrations, all the AMI patients were divided into the high-level group (TSLP level ≥ 11.18 pg/ml, N = 91) and the low-level group (TSLP <11.18 pg/ml, N = 84). In a receiver operating characteristic curve analysis, the area under the curve for TSLP as a predictor of AMI was 0.674 with a cut-off value of 9.235 pg/ml. After a median follow-up of 14 months, Kaplan-Meier survival analysis showed no significant difference in MACE-free survival between the two groups (p = 0.648). Finally, the multivariate logistic regression analyses demonstrated that TSLP was a negative predictor of MACE in AMI patients (OR:0.778,95% CI:0.733–0.876, p = 0.032).ConclusionsPlasma TSLP levels were elevated in patients with AMI than those in UA. The lower TSLP concentration was associated with MACE after AMI.

Peroxiredoxin2 (Prdx2) Reduces Oxidative Stress and Apoptosis of Myocardial Cells Induced by Acute Myocardial Infarction by Inhibiting the TLR4/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BackgroundPeroxiredoxin2 (Prdx2) is an endogenous peroxidase and has been found to reduce the oxidative burden in cells and thereby reduce cell damage and apoptosis. Therefore, the purpose of this study was to investigate the effect of Prdx2 on the oxidative level and apoptosis of myocardial cells after acute myocardial infarction (AMI).Material/MethodsWe constructed an AMI model for Sprague-Dawley rats by ligating the left anterior descending coronary artery. We determined the effect of Prdx2 on AMI by detecting changes in Prdx2 in myocardial tissue via western blot and qRT-PCR. In addition, we used recombinant Prdx2 protein to treat rats and detect changes in oxidative stress and apoptosis in rat myocardial tissue to verify the protective effect of Prdx2 on the rat heart.ResultsThe protein and mRNA expression of Prdx2 in myocardial tissue of rats in the AMI group was significantly lower than that in the control group. The oxidative and apoptotic levels of myocardial tissue in Prdx2-administered rats were significantly improved compared to the non-administered group, which was manifested by a decrease in reactive oxygen species (ROS) levels and a decrease in the expression of the caspase family. In addition, Prdx2 also inhibited p65 phosphorylation in myocardial tissues and inhibited TLR4/NF-κB signaling pathway activity.ConclusionsThe expression of Prdx2 was decreased in myocardial tissue after AMI. Prdx2 can reduce apoptosis and ROS caused by AMI by inhibiting the TLR4/NF-κB signaling pathway, thereby reducing myocardial injury caused by AMI.

Astaxanthin promotes M2 macrophages and attenuates cardiac remodeling after myocardial infarction by suppression inflammation in rats.

BackgroundCardiac remodeling after acute myocardial infarction (AMI) is an important process. The present study aimed to assess the protective effects of astaxanthin (ASX) on cardiac remodeling after AMI.MethodsThe study was conducted between April and September 2018. To create a rat AMI model, rats were anesthetized, and the left anterior descending coronary artery was ligated. The rats in the ASX group received 10 mg·kg−1·day−1 ASX by gavage for 28 days. On the 1st day after AMI, but before ASX administration, six rats from each group were sacrificed to evaluate changes in the heart function and peripheral blood (PB) levels of inflammatory factors. On the 7th day after AMI, eight rats from each group were sacrificed to evaluate the PB levels of inflammatory factors and the M2 macrophage count using both immunofluorescence (IF) and flow cytometry (FC). The remaining rats were observed for 28 days. Cardiac function was examined using echocardiography. The inflammatory factors, namely, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, were assessed using enzyme-linked immunosorbent assay. The heart weight/body weight (BW), and lung weight (LW)/BW ratios were calculated, and myocardial fibrosis in the form of collagen volume fraction was measured using Masson trichrome staining. Hematoxylin and eosin (H&E) staining was used to determine the myocardial infarct size (MIS), and TdT-mediated dUTP nick-end labeling staining was used to analyze the myocardial apoptosis index. The levels of apoptosis-related protein, type I/III collagen, transforming growth factor β1 (TGF-β1), metalloproteinase 9 (MMP9), and caspase 3 were assessed by Western blotting. Unpaired t-test, one-way analysis of variance, and non-parametric Mann-Whitney test were used to analyze the data.ResultsOn day 1, cardiac function was worse in the ASX group than in the sham group (left ventricular end-systolic diameter [LVIDs]: 0.72 ± 0.08 vs. 0.22 ± 0.06 cm, t = −11.38; left ventricular end-diastolic diameter [LVIDd]: 0.89 ± 0.09 vs. 0.48 ± 0.05 cm, t = −9.42; end-systolic volume [ESV]: 0.80 [0.62, 0.94] vs. 0.04 [0.03, 0.05] mL, Z = −2.89; end-diastolic volume [EDV]: 1.39 [1.03, 1.49] vs. 0.28 [0.22, 0.32] mL, Z = −2.88; ejection fraction [EF]: 0.40 ± 0.04 vs. 0.86 ± 0.05, t = 10.00; left ventricular fractional shortening [FS] rate: 0.19 [0.18, 0.20] %FS vs. 0.51 [0.44, 0.58] %FS, Z = −2.88, all P < 0.01; n = 6). The levels of inflammatory factors significantly increased (TNF-α: 197.60 [133.89, 237.94] vs. 50.48 [47.21 57.10] pg/mL, Z = −2.88; IL-1β: 175.23 [160.74, 215.09] vs. 17.78 [16.83, 19.56] pg/mL, Z = −2.88; IL-10: 67.64 [58.90, 71.46] vs. 12.33 [11.64, 13.98] pg/mL, Z = −2.88, all P < 0.01; n = 6). On day 7, the levels of TNF-α and IL-1β were markedly lower in the ASX group than in the AMI group (TNF-α: 71.70 [68.60, 76.00] vs. 118.07 [106.92, 169.08] pg/mL, F = 42.64; IL-1β: 59.90 [50.83, 73.78] vs. 151.60 [108.4, 198.36] pg/mL, F = 44.35, all P < 0.01, n = 8). Conversely, IL-10 levels significantly increased (141.84 [118.98, 158.36] vs. 52.96 [42.68, 74.52] pg/mL, F = 126.67, P < 0.01, n = 8). The M2 macrophage count significantly increased (2891.42 ± 211.29 vs. 1583.38 ± 162.22, F = 274.35, P < 0.01 by immunofluorescence test; 0.96 ± 0.18 vs. 0.36 ± 0.05, F = 46.24, P < 0.05 by flowcytometry test). On day 28, cardiac function was better in the ASX group than in the AMI group (LVIDs: 0.50 [0.41, 0.56] vs. 0.64 [0.56, 0.74] cm, Z = −3.60; LVIDd: 0.70 [0.60, 0.76] vs. 0.80 [0.74 0.88] cm, Z = −2.96; ESV: 0.24 [0.18, 0.45] vs. 0.58 [0.44, 0.89] mL, Z = −3.62; EDV: 0.76 [0.44, 1.04] vs. 1.25 [0.82, 1.46] mL, Z = −2.54; EF: 0.60 ± 0.08 vs. 0.50 ± 0.12, F = 160.48; %FS: 0.29 [0.24, 0.31] vs. 0.20 [0.17, 0.21], Z = −4.43, all P < 0.01; n = 16). The MIS and LW/BW ratio were markedly lower in the ASX group than in the AMI group (myocardial infarct size: 32.50 ± 1.37 vs. 50.90 ± 1.73, t = 23.63, P < 0.01, n = 8; LW/BW: 1.81 ± 0.15 vs. 2.17 ± 0.37, t = 3.66, P = 0.01, n = 16). The CVF was significantly lower in the ASX group than in the AMI group: 12.88 ± 2.53 vs. 28.92 ± 3.31, t = 10.89, P < 0.01, n = 8. The expression of caspase 3, TGF-β1, MMP9, and type I/III collagen was lower in the ASX group than in the AMI group (caspase 3: 0.38 ± 0.06 vs. 0.66 ± 0.04, t = 8.28; TGF-β1: 0.37 ± 0.04 vs. 0.62 ± 0.07, t = 6.39; MMP9: 0.20 ± 0.06 vs. 0.40 ± 0.06, t = 4.62; type I collagen: 0.42 ± 0.09 vs. 0.74 ± 0.07, t = 5.73; type III collagen: 0.13 ± 0.02 vs. 0.74 ± 0.07, t = 4.32, all P < 0.01; n = 4).ConclusionsASX treatment after AMI may promote M2 macrophages and effectively attenuate cardiac remodeling by inhibiting inflammation and reducing myocardial fibrosis.

Losartan promotes myocardial apoptosis after acute myocardial infarction in rats through inhibiting Ang II-induced JAK/STAT pathway.

To study the pro-apoptotic effect of Losartan on myocardial cells after acute myocardial infarction (AMI) in rats. Before intervention, a total of 48 male Wistar rats were randomly divided into the Sham group (n=12), AMI group (n=12), 5 mg/kg Losartan group (n=12) and 1 mg/kg AG-490 group (n=12). The rats in the Sham group and AMI group received gavage with normal saline, those in the Losartan group received gavage with Losartan for 7 d and those in the AG-490 group were intravenously injected with AG-490 at 30 min before the operation. At 4 d after drug administration, the anterior descending coronary artery was ligated to establish the AMI model in the AMI group and Losartan group, while the same operation was performed, and the anterior descending coronary artery was only threaded in the Sham group. The rats were sacrificed at 24 h after operation. Then, the myocardial apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the protein expressions of Janus kinase 2 (JAK2), the signal transducer and activator of transcription 3 (STAT3), the B-cell lymphoma-2 (Bcl-2) and the Bcl-2 associated X protein (Bax) were detected via immunohistochemistry and Western blotting. Moreover, the myocardial cells of rats were incubated with angiotensin II (Ang II) at the same concentration at different time points and blocked with Losartan. Finally, the changes in protein expressions of p-JAK2, p-STAT3, Bax, and Bcl-2 were detected via Western blotting. Losartan treatment could increase the number of apoptotic myocardial cells after AMI in rats. In Losartan group, the protein expressions of JAK2, STAT3, and Bcl-2 declined, while the protein expression of Bax was increased, and the Bax/Bcl-2 ratio was also increased, which are consistent with the conditions under the treatment with the JAK-STAT pathway inhibitor AG-490. With the prolonged time of stimulation (5 min, 30 min, 2 h, and 24 h) in myocardial cells using 1.0×10-6 mol/L Ang II, the protein expressions of p-JAK2 and p-STAT3 were increased and reached the peak at 24 h. After the application of Losartan, the increased protein expressions of p-JAK2 and p-STAT3 returned to normal levels, and the protein expression of Bax was increased, while that of Bcl-2 was decreased. Losartan promotes myocardial apoptosis after AMI in the rats through inhibiting the Ang II-induced JAK/STAT pathway.

Recovery of Left Ventricular Twist and Left Ventricular Untwist Rate in Patients with ST-segment Elevation Acute Myocardial Infarction

Background: Left ventricular (LV) functional recovery and morphological remodeling after acute myocardial infarction (AMI) followed by reperfusion remain incompletely understood. The aim of the study was to describe the recovery of LV twist (LVT) and LV untwist rate (LVUR) upon revascularization after AMI using two-dimensional (2D) speckle tracking. Methods: We evaluated 88 subjects: 22 normal volunteers (mean age 31 ± 5 years), and 66 patients with AMI (mean age 65 ± 12 years), of which 40 had an inferior AMI and 26 an anterior one. All AMI patients had ST-segment elevation. Echocardiography was performed in all subjects. Patients were scanned within 36 h (baseline) after revascularization (percutaneous coronary intervention) and after 4 months (4 mFU). Apical and basal short-axis images were acquired (frame rate 67 ± 5 frames/s) and analyzed offline to extract the rotation (rate) curves. From these, maximal systolic LVT and peak LVUR were derived. Finally, the infarct size (IS) was estimated based on magnetic resonance imaging delayed enhancement and expressed as a percentage of the total LV volume. Results: At 36 h, LVT and LVUR were significantly reduced in both AMI groups when compared to normals. At 4 mFU, both AMI groups showed recovery in ejection fraction (EF) and reduction in IS (7.24 ± 10.07 vs. 20.13 ± 13.9, P &lt; 0.0001 for inferior AMI and 13.13 ± 10.3 vs. 24.40 ± 15, P &lt; 0.0001 for anterior AMI). LVT and LVUR increased significantly but remained below normal levels. Correlation of LVT and LVUR with IS was significant, but weak (r = 0.34 and r = 0.34, respectively). In addition, a fair correlation of LVT with EF (r = 0.64) and a weak correlation of LVUR with end-diastolic volume (r = 0.43) were found. Conclusion: LVT and LVUR are reduced in AMI patients early after reperfusion and recover incompletely upon follow-up. Interestingly, recovery of LVT characteristics as measured with this 2D speckle tracking-based method showed to be independent of infarct location or extent. LVT and LVUR might be good parameters to monitor the recovery of global LV function after treatment.

PO-161 Effect of different type of exercise on mitochondrial homeostasis in rats with myocardial infarction

Objective To investigate the different effect of moderate-intensity continuous training (MCT) and high-intensity interval exercise training (HIT) on ventricular remodeling and mitochondrial homeostasis after acute myocardial infarction (AMI).&#x0D; Methods The AMI rat model was achieved by ligating coronary artery. The AMI and sham operation rats were randomly divided into four groups: sham operation group (Sham), AMI control group (AMI), AMI MCT group (AMI+M), and AMI HIT group (AMI+H). Animals in the AMI+M and AMI+H groups underwent 4 weeks MCT and HIT respectively. Five weeks after AMI, hemodynamic changes, mitochondrial bioenergetics, and PINK1, Beclin1, Mfn2, Drp1, Tfam, COXⅣ, PGC-1α were detected.&#x0D; Results Comparing with AMI group, in AMI+M and AMI+H groups, Beclin1 (146.33±18.47, 143.28±16.96.vs. 123.27±13.27, P&lt;0.05), PINK1 (150.33±20.54, 152.28±18.34.vs. 125.27±17.67, P&lt;0.05), Mfn2 (122.28±18.81, 117.19±17.04.vs. 46.27±6.72, P&lt;0.01), and PGC-1α (82.15±16.58, 102.25±13.27.vs. 60.27±9.36, P&lt;0.05~0.01) expression elevated significantly, whereas ROS generation (122.28±18.81, 117.19±17.04.vs. 46.27±6.72, P&lt;0.01) and Drp1 expression (9.58±1.40, 10.18±1.37.vs. 15.85±1.61, P&lt;0.05) showed dramatic decrease. In addition, in AMI+H group, +dp/dt max (6326±325.vs. 5368±271, P&lt;0.05), -dp/dt max (-5312±246.vs. -4457±250, P&lt;0.05), mitochondrial membrane potential (85.24±11.94.vs. 71.28±8.34, P&lt;0.05), ATP synthesis activity (38.77±5.16.vs. 32.33±4.14, P&lt;0.05), Tfam (95.25±12.05.vs. 78.27±12.22, P&lt;0.05) and COXⅣ (89.25±14.06.vs. 67.27±13.71, P&lt;0.05) expression improved significantly. Comparing with AMI+M group, in AMI+H group, +dp/dt max (6326±325.vs. 5775±310, P&lt;0.05), -dp/dt max (-5312±246.vs. -4778±305, P&lt;0.05), PGC-1α (102.25±13.27.vs. 82.15±16.58 1, P&lt;0.05), Tfam (95.25±12.05.vs. 80.15±11.99, P&lt;0.05) and COXⅣ(89.25±14.06.vs. 72.15±10.89, P&lt;0.05) expression improved significantly.&#x0D; Conclusions High-intensity interval exercise training is superior to moderate-intensity continuous training for ameliorating ventricular remodeling and mitochondrial homeostasis after acute myocardial infarction.

Long-Term Outcomes of Acute Myocardial Infarction in Patients With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with poor prognosis. It has been reported that there is no difference in in-hospital mortality after acute myocardial infarction (AMI) between patients with and without HCM. However, whether there are differences in long-term outcomes after AMI between patients with and without HCM remains unclear. In this study, we analyzed the clinical profiles of 78 consecutive patients with HCM and AMI (HCM and AMI group), 78 sex- and age-matched patients with AMI and without HCM (AMI group), and 78 sex- and age-matched patients with HCM and without AMI (HCM group). The study end points were major adverse cardiac events (MACEs) and secondary end points. During the follow-up period of 4.8 ± 3.6 years, MACEs occurred in 19 (27.9) patients in the HCM and AMI group, in 11 (16.7%) patients in the AMI group, and in 8 (12.3%) patients in the HCM group. The long-term outcomes of the HCM and AMI group were inferior to that of the other 2 groups (log-rank P = .030 for MACEs, log-rank P = .032 for secondary end points). In conclusion, patients with AMI with HCM exhibited worse long-term outcomes than did patients with AMI without HCM and patients with HCM without AMI.

Cardiac shock wave therapy promotes arteriogenesis of coronary micrangium, and ILK is involved in the biomechanical effects by proteomic analysis

Cardiac Shock Wave Therapy (CSWT) improves myocardial perfusion and ameliorates cardiac remodeling after acute myocardial infarction (AMI), but the precise mechanisms remain obscure. Herein, we have applied CSWT to a rat model of AMI to demonstrate the arteriogenesis of coronary micrangium and protein expression changes in ischemic myocardium after CSWT. Four weeks after CSWT, the fraction shortening of rats was improved greatly and the cardiomyocyte apoptosis index was significantly lower than the AMI group (P < 0.05). Besides, the fibrotic area was markedly decreased in the CSWT group. In the infarction border zone, the thickness of smooth muscle layer was expanded apparently after CSWT. Label-free quantitative proteomic analysis and bioinformatics analysis revealed that the differentially expressed proteins were largely enriched in the focal adhesion signaling pathway. And integrin linked kinase (ILK) may be a key factor contributed to arteriogenesis of coronary micrangium during CSWT. In conclusion, non-invasive cardiac shock wave could promote arteriogenesis of coronary micrangium and alleviate myocardial apoptosis and fibrosis after AMI. Furthermore, focal adhesion signaling pathway may have a central role in the related signal network and ILK was closely related to the arteriogenesis of coronary micrangium during CSWT.

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-β1 Signaling Pathway.

Myocardial fibrosis after acute myocardial infarction (AMI) is one of the main causes of myocardial remodeling and heart function abnormalities. Bone morphogenetic protein-7 (BMP-7) has been reported to play essential roles in anti-fibrosis. In this study, we demonstrated the role of exogenous BMP-7 on myocardial fibrosis and heart function recovery after AMI. A rat model of AMI was established via ligation of the left anterior descending coronary artery (LAD). Twenty rats were grouped into sham group which underwent chest open operation, but did not receive LAD ligation. Another 40 rats underwent LAD ligation were randomly grouped into saline-treated group (n = 20) and BMP-7-treated group (n = 20) which received saline treatment or exogenous BMP-7 treatment for 14 days, respectively. Two weeks after LAD ligation, the survival rate of BMP-7-treated AMI group was significantly improved compared to the saline group. Moreover, the cardiac function was preserved as shown by echocardiography examination, and the infarcted size was limited upon BMP-7 treatment. In addition, we investigated the role of TGF-β1 signaling pathway in BMP-7-mediated cardioprotective effects by analyzing the expression levels of TGF-β1, Smad 2 and Smad 3 in the infarct zone, border zone, and non-infarct zone. Western blot and quantitative PCR results suggested that BMP-7 attenuated myocardial fibrosis through counteracting TGF-β1 signaling pathway, thereby exerting cardioprotective effects. In conclusion, our data provide a potential therapeutic direction for preserving cardiac function and improving prognosis of AMI patients.

Effect of different type of exercise on mitochondrial homeostasis in rats with myocardial infarction

Objective To investigated the different effect of moderate-intensity continuous training (MCT) and high-intensity interval exercise training (HIT) on ventricular remodeling and mitochondrial homeostasis after acute myocardial infarction (AMI). Methods The AMI rat model was achieved by ligating coronary artery. The AMI and sham operation rats were randomly(random number) divided into four groups: sham operation group (Sham), AMI control group (AMI), AMI MCT group (AMI+ M), and AMI HIT group (AMI+ H). Animals in the AMI+ M and AMI+ H groups underwent 4 weeks MCT and HIT respectively. Five weeks after AMI, hemodynamic changes, mitochondrial bioenergetics, and PINK1, Beclin1, Mfn2, Drp1, Tfam, COXⅣ, PGC-1α were detected. Results Comparing with AMI group, in AMI+ M and AMI+ H groups, Beclin1, PINK1, Mfn2 and PGC-1α expression elevated significantly (P<0.05 or P<0.01), whereas ROS generation and Drp1 expression showed dramatic decrease (P<0.05 or P<0.01). In addition, in AMI+ H group, ±dp/dt max, mitochondrial membrane potential, ATP synthesis activity, Tfam and COXⅣexpression improved significantly (P<0.05). Comparing with AMI+ M group, in AMI+ H group, ±dp/dt max, PGC-1α, Tfam and COX Ⅳ expression improved significantly (P<0.05). Conclusions HIT is superior to MCT for ameliorating ventricular remodeling and mitochondrial homeostasis after AMI. Key words: Acute myocardial infarction; High-intensity interval exercise training; Moderate-intensity continuous training; Ventricular remodeling; Mitochondrial homeostasis

Long-Term Outcomes After Coronary Stent Implantation in Patients Presenting With Versus Without Acute Myocardial Infarction (an Observation from Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2)

It has not been adequately addressed yet how long the excess cardiovascular event risk persists after acute myocardial infarction (AMI) compared with stable coronary artery disease. Of 10,470 consecutive patients who underwent percutaneous coronary intervention either with sirolimus-eluting stent (SES) only or with bare-metal stent (BMS) only in the Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2, 3,710 (SES: n = 820 and BMS: n = 2,890) and 6,760 patients (SES: n = 4,258 and BMS: n = 2,502) presented with AMI (AMI group) and without AMI (non-AMI group), respectively. During the median 5-year follow-up, the excess adjusted risk of the AMI group relative to the non-AMI group for the primary outcome measure (cardiac death or myocardial infarction) was significant (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.30 to 1.80, p <0.001). However, the excess event risk was limited to the early period within 3 months. Late adjusted risk beyond 3 months was similar between the AMI and non-AMI groups (HR 1.16, 95% CI 0.95 to 1.41, p = 0.15). The higher risk of the AMI group relative to the non-AMI group for stent thrombosis (ST) was significant within 3 months (HR 3.38, 95% CI 2.04 to 5.60, p <0.001), whereas the risk for ST was not different between the 2 groups beyond 3 months (HR 1.11, 95% CI 0.65 to 1.90, p = 0.70). There were no interactions between the types of stents implanted and the risk of the AMI group relative to the non-AMI groups for all the outcome measures including ST. In conclusion, patients with AMI compared with those without AMI were associated with similar late cardiovascular event risk beyond 3 months after percutaneous coronary intervention despite their higher early risk within 3 months.

Paradoxical sleep deprivation increases mortality in myocardial infarcted rats

We hypothesized that sleep deprivation affects hemodynamic parameters and, therefore, correlates with mortality after acute myocardial infarction (AMI) induced by isoproterenol. Rats were randomly assigned to one of four experimental groups: control, paradoxical sleep deprivation (PSD), AMI, and PSD + AMI. Blood pressure, heart rate and renal sympathetic nerve activity were higher in the PSD group. Mortality after isoproterenol administration was significantly higher in the PSD + AMI group compared to the AMI group. These data suggest that sleep loss is able to increase cardiovascular risk, per se, and worsens the prognosis in cases of cardiac insult.

Extracorporeal cardiac shock wave therapy ameliorates myocardial fibrosis by decreasing the amount of fibrocytes after acute myocardial infarction in pigs

Extracorporeal shock wave (SW) therapy ameliorates cardiac remodeling after acute myocardial infarction (AMI). However, it remains to be examined whether and how SW therapy ameliorates myocardial fibrosis after AMI. Fibrocytes are associated with myocardial fibrosis. Thus, we examined whether SW therapy ameliorates myocardial fibrosis and whether fibrocytes are associated after AMI in pigs. AMI was created by coronary embolism. Twenty-five pigs were divided into three groups: AMI+SW group (AMI with SW therapy, n=15), AMI group (without SW therapy, n=5), and sham+SW group (SW therapy without AMI, n=5). The collagen area fraction was examined by Masson's trichrome staining. The presence of fibrocytes was identified by immunofluorescence and confocal microscopy. The location of CXCL12 was examined by immunohistochemistry. Compared with the AMI group, the AMI+SW group showed significantly ameliorated myocardial fibrosis in terms of collagen area fraction (27.21±8.13 vs. 10.13±4.96, P<0.05) and reduced fibrocytes (CD34/α-smooth muscle actin: 35.40±11.72 vs. 12.27±7.71, P<0.05; CXCR4/α-smooth muscle actin: 40.80±8.96 vs. 16.54±6.38, P<0.05). There were positive correlations between the collagen area fraction and the number of fibrocytes (r=0.936; P<0.05) and between the number of CXCR4 fibrocytes and the SDF-1/CXCL12 cells (r=0.802; P<0.05) in the three groups. The results show that SW therapy ameliorates myocardial fibrosis after AMI in pigs, which is associated with the decreased amount of fibrocytes.

Cardiopulmonary exercise testing in the early-phase of myocardial infarction

To evaluate and to compare the cardiorespiratory and metabolic variables at the ventilatory anaerobic threshold level (AT) and at submaximal cardiopulmonary exercise testing (CPET) in both, healthy volunteers and in patients in the early phase after acute myocardial infarction (AMI). Twenty-six volunteers underwent a submaximal or symptom-limited cardiopulmonary exercise testing (CPET) on a cycle ergometer and were divided into AMI group (AMIG=12, 56.33±8.65 years) and healthy group (CG=14, 53.33±3.28 years). The primary outcome measures were the cardiorespiratory and metabolic variables obtained at the peak workload and at the AT of the CPET. Statistical test: independent Student's t-test, α=5%. The AMIG presented lower values at the AT and the peak workload of the CPET compered to the CG: power in watts (91.06±30.10 and 64.88±19.92; 154.93±34.65 and 120.40±29.60); VO2 mL.kg-1.min-1 (17.26±2.71 and 12.19±2.51; 25.39±5.73 and 19.41±5.63); VCO2 L/min-1 (1.43±0.31 and 0.93±0.23; 2.07±0.43 and 1.42±0.36), VO2 L/min-1 (1.33±0.32 and 1.00±0.23; 1.97±0.39 and 1.49±0.36); VE L/min-1 (42.13±8.32 and 27.51±5.86; 63.07±20.83 and 40.82±11.96); HR (bpm) (122.96±14.02 and 103.46±13.38; 149.67±13.77 and 127.60±10.04), double product (DP) (bpm.mmHg.min-1) (21835.86±3245.93 and 17333.25±2716.51; 27302.33±3053.08 and 21864.00±2051.48), respectively. The variable oxygen uptake efficiency slope (OUES L/min) was lower in the AMIG (1.79±0.51) than the CG (2.26±0.37). The AMIG presented neither ECG alterations nor symptoms that limited the CPET. The results suggest that patients with AMI Killip class I presented lower functional capacity and DP compared to the CG without presenting ischemic alterations. Thus, the study suggests that submaximal CPET can be applied at an early stage to evaluate cardiorespiratory status since it is both safe and highly sensitive to detect changes.

Linear and nonlinear analysis of heart rate variability in healthy subjects and after acute myocardial infarction in patients

The objectives of this study were to evaluate and compare the use of linear and nonlinear methods for analysis of heart rate variability (HRV) in healthy subjects and in patients after acute myocardial infarction (AMI). Heart rate (HR) was recorded for 15 min in the supine position in 10 patients with AMI taking β-blockers (aged 57 ± 9 years) and in 11 healthy subjects (aged 53 ± 4 years). HRV was analyzed in the time domain (RMSSD and RMSM), the frequency domain using low- and high-frequency bands in normalized units (nu; LFnu and HFnu) and the LF/HF ratio and approximate entropy (ApEn) were determined. There was a correlation (P < 0.05) of RMSSD, RMSM, LFnu, HFnu, and the LF/HF ratio index with the ApEn of the AMI group on the 2nd (r = 0.87, 0.65, 0.72, 0.72, and 0.64) and 7th day (r = 0.88, 0.70, 0.69, 0.69, and 0.87) and of the healthy group (r = 0.63, 0.71, 0.63, 0.63, and 0.74), respectively. The median HRV indexes of the AMI group on the 2nd and 7th day differed from the healthy group (P < 0.05): RMSSD = 10.37, 19.95, 24.81; RMSM = 23.47, 31.96, 43.79; LFnu = 0.79, 0.79, 0.62; HFnu = 0.20, 0.20, 0.37; LF/HF ratio = 3.87, 3.94, 1.65; ApEn = 1.01, 1.24, 1.31, respectively. There was agreement between the methods, suggesting that these have the same power to evaluate autonomic modulation of HR in both AMI patients and healthy subjects. AMI contributed to a reduction in cardiac signal irregularity, higher sympathetic modulation and lower vagal modulation.