Inhibition of thyroid hormone receptor α1 impairs post-ischemic cardiac performance after myocardial infarction in mice

Thyroid hormone receptor α1 (TRα1) is shown to be critical for the maturation of cardiomyocytes and for the cellular response to stress. TRα1 is altered during post ischemic cardiac remodeling but the physiological significance of this response is not fully understood. Thus, the present study explored the potential consequences of selective pharmacological inhibition of TRα1 on the mechanical performance of the post-infarcted heart. Acute myocardial infarction was induced in mice (AMI), while sham operated animals served as controls (SHAM). A group of mice was treated with debutyl-dronedarone (DBD), a selective TRα1 inhibitor (AMI–DBD). AMI resulted in low T3 levels in plasma and in down-regulation of TRα1 and TRβ1 expression. Left ventricular ejection fraction (LVEF%) was significantly reduced in AMI [33 (SEM 2.1) vs 79(2.5) in SHAM, p < 0.05] and was further declined in AMI–DBD [22(1.1) vs 33(2.1), respectively, p < 0.05]. Cardiac mass was increased in AMI but not in AMI–DBD hearts, resulting in significant increase in wall tension index. This increase in wall stress was accompanied by marked activation of p38 MAPK, a kinase that is sensitive to mechanical stretch and exerts negative inotropic effect. Furthermore, AMI resulted in β-myosin heavy chain overexpression and reduction in the ratio of SR(Ca)ATPase to phospholamban (PLB). The latter further declined in AMI–DBD mainly due to increased expression of PLB. AMI induces downregulation of thyroid hormone signaling and pharmacological inhibition of TRα1 further depresses post-ischemic cardiac function. p38 MAPK and PLB may, at least in part, be involved in this response.     

Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings

The present study explored the effects of thyroid hormone (TH) treatment on post-ischemic cardiac function and potential implicated mechanisms. Acute myocardial infarction (AMI) was induced in mice by coronary artery ligation while sham-operated animals served as controls. This procedure resulted in a marked depression of cardiac function and significant reduction in TH levels in plasma. TH was given at a dose aiming to normalize T3 levels in plasma [AMI-TH (A)] and also at higher doses. The group of animals treated with the highest dose of TH, which displayed significantly increased mortality rate was included in the study [AMI-TH (B)]. In AMI-TH (A) mice, TH significantly improved left ventricular (LV) ejection fraction (EF%), [27.9% (1.4) in AMI versus 38.0 (3.1) in AMI-TH (A), P < 0.05], and favorably remodeled LV chamber while α-MHC was the dominant isoform expressed. In AMI-TH (B) mice, TH treatment resulted in increased mortality as compared to untreated mice (73% vs 47%, P < 0.05), while the favorable effect of TH was not evident in the survived animals. At the molecular level, TH, at the replacement dose, modestly increased p-Akt levels in the myocardium without any change in p-ERK levels. On the contrary, TH at the higher dose resulted in further increase in p-Akt along with an increase in p-ERK levels. In conclusion, TH appears to have a dose-dependent bimodal effect on post-ischemic cardiac performance and this effect may, at least in part, be mediated by a distinct pattern of activation of Akt and ERK signaling.     

Nebulized Delivery of the MAPKAP Kinase 2 Peptide Inhibitor MMI-0100 Protects Against Ischemia-Induced Systolic Dysfunction

Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI-0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI induced by left-anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI-0100: inhalation of nebulized peptide. When given within 30 min of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI-0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after 2 weeks by Massons trichrome staining, suggesting that MMI-0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI-0100 can protect the myocardium from ischemic damage.     

曲美他嗪联合麝香保心丸治疗急性心肌梗死的效果研究

目的:研究曲美他嗪(TMZ)联合麝香保心丸(HMP)治疗急性心肌梗死的效果。方法:采用40只雄性C57BL/6J小鼠构建急性心肌梗死模型,随机分成4组,每组10只:(1)假手术组;(2)心肌梗死组;(3)心肌梗死+TMZ组(TMZ 20 mg/Kg灌胃,3次/天);(4)心肌梗死+TMZ+HMP组(HMP 14 mg/Kg灌胃,3次/天)。2周后行心脏超声检查采集心功能参数左室舒张末内径、左室收缩末内径、室间隔厚度、舒张末期左室后壁厚度及射血分数。同时,对心脏标本行形态学分析。结果:TMZ+HMP组左室舒张末内径、左室收缩末内径、舒张末期左室后壁厚度及射血分数均优于于TMZ组(均为P0.05)。心肌组织HE及PSR染色显示TMZ+HMP组心肌细胞坏死及纤维化程度较其余组低。结论:曲美他嗪联合麝香保心丸治疗急性心肌梗死的效果较单用曲美他嗪更加显著。     

共载体AAV-PR39-ADM治疗缺血性心脏病

目的:探讨共载体AAV-PR39-ADM分泌表达血管生成肽(PR39)与血管扩张肽(ADM)对SD大鼠心肌缺血再灌注损伤的作用。方法:选健康成年雄性SD大鼠36只,体重平均为280 g±20 g,随机分为假手术组(SO)、治疗组(TR)与对照组(I/R),每组各12只。治疗组大鼠心肌注射共载体AAV-PR39-ADM感染心肌7天后行B超检查,测量记录左室壁厚度及射血分数(EF%),左室收缩末压(LVSP),左室内压最大上升下降速率(±dp/dt max)评价作为心脏功能指标。对照组建立缺血再灌注损伤模型,假手术组只穿线不结扎且两组行相同检测。速取处死大鼠心肌行masson染色测量心肌梗死面积。结果:治疗组明显高于对照组,其射血分数、左室内收缩末压、最大上升速率,最大下降速率、梗死面积分别为:EF%(50.4±6.3),(29.8±10.5),P0.05;LVSP:(116±4.2),(101±3.7),P0.05;+dp/dt max:(2859±365),(2137±191),P0.05;-dp/dtmax:(2186±107),(1886±124),P0.05;IS%:(29.3±4.6),(24.6±2.2),P0.05。结论:共载体AAV-PR39-ADM能够显著恢复心肌缺血损伤引起的左室内压下降,提高心肌收缩能力,提高射血分数并明显缩小心肌梗死范围。     

Predictive value of circulating miR-328 and miR-134 for acute myocardial infarction

MicroRNA (miRNAs) is demonstrated to be present in the blood of humans and has been increasingly suggested as a novel biomarker for various pathological processes in the heart, including myocardial infarction, myocardial remodeling and progression to heart failure. In this study, we aim to evaluate the diagnostic and prognostic value of circulating miR-328 and miR-134 in patients with acute myocardial infarction (AMI). Circulating levels of miR-328 and miR-134 were detected by quantitative real-time PCR in plasma samples from 359 AMI patients and 30 healthy volunteers. Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) were measured using electrochemiluminescence-based methods. MiRNAs were assessed for discrimination of a clinical diagnosis of AMI and for association with primary clinical endpoint defined as a composite of cardiogenic death and development of heart failure within 6 months after infarction. Results showed that levels of plasma miR-328 and miR-134 were significantly higher in AMI patients than in healthy controls. Receiver operating characteristic curve analyses showed significant diagnostic value of miR-328 and miR-134 for AMI. However, neither of them was superior to hs-cTnT for the diagnosis. Additionally, increased miRNA levels were strongly associated with increased risk of mortality or heart failure within 6 months for miR-328 (OR 7.35, 95 % confidence interval 1.07–17.83, P < 0.001) and miR-134 (OR 2.28, 95 % confidence interval 1.03–11.32 P < 0.001). In conclusion, circulating miR-328 and miR-134 could be potential indicators for AMI, and the miRNA levels are associated with increased risk of mortality or development of heart failure.     

Multi-modality imaging evaluation of recurrent Tako-tsubo syndrome in a patient with coronary artery fibromuscular dysplasia

Background

Integrated bedside and sophisticated cardiac imaging techniques help characterize the discrepancy between myocardial injury and mechanic dysfunction in acute myocardial infarction.

Case presentation

A 57 year-old woman presented with sudden onset chest pain and ventricular fibrillation after hearing of her brother’s death. The electrocardiography indicated “anterior wall ST segment elevation myocardial infarction”. Coronary angiography ruled out obstructive lesion in the major coronary arteries, but revealed fibromuscular dysplasia of the distal left anterior descending artery. The ventriculography showed remarkable ventricular dilation, which affected much broader myocardium than the culprit vessel supplied. In a subsequent cardiac magnetic resonance study, delayed contrast (gadolinium) image revealed a focal left ventricular (LV) apical infarction. Her LV systolic function normalized within 1 week, except for a residual apical hypokinesis. She developed recurrent chest pain and LV dilation when she was laid off 9 months later. After supportive therapy, her symptoms improved and LV dysfunction normalized again.

Conclusions

“Tako-tsubo” syndrome can occur recurrently in the heart with pre-existing localized myocardial infarction. Its molecular mechanism and clinical significance warrants further investigation.

     

The non-invasive documentation of coronary microcirculation impairment: role of transthoracic echocardiography

Background

Multiples indices have been described using tissue Doppler imaging (DTI) capabilities. The aim of this study was to assess the capability of one or several regional DTI parameters in separating control from ischemic myocardium.

Methods

Twenty-eight patients with acute myocardial infarction were imaged within 24-hour following an emergent coronary angioplasty. Seventeen controls without any coronary artery or myocardial disease were also explored. Global and regional left ventricular functions were assessed. High frame rate color DTI cineloop recordings were made in apical 4 and 2-chamber for subsequent analysis. Peak velocity during isovolumic contraction time (IVC), ejection time, isovolumic relaxation (IVR) and filling time were measured at the mitral annulus and the basal, mid and apical segments of each of the walls studied as well as peak systolic displacement and peak of strain.

Results

DTI-analysis enabled us to discriminate between the 3 populations (controls, inferior and anterior AMI). Even in non-ischemic segments, velocities and displacements were reduced in the 2 AMI populations. Peak systolic displacement was the best parameter to discriminate controls from AMI groups (wall by wall, p was systematically < 0.01). The combination IVC + and IVR< 1 discriminated ischemic from non-ischemic segments with 82% sensitivity and 85% specificity.

Conclusion

DTI-analysis appears to be valuable in ischemic heart disease assessment. Its clinical impact remains to be established. However this simple index might really help in intensive care unit routine practice.     

Thyroid hormone and cardiac repair/regeneration: from Prometheus myth to reality?

Nature's models of repair and (or) regeneration provide substantial evidence that a natural healing process may exist in the heart. The potential for repair and (or) regeneration has been evolutionarily conserved in mammals, and seems to be restricted to the early developmental stages. This window of regeneration is reactivated during the disease state in which fetal gene reprogramming occurs in response to stress. Analogies exist between the damaged and developing heart, indicating that a regulatory network that drives embryonic heart development may control aspects of heart repair and (or) regeneration. In this context, thyroid hormone (TH), which is a critical regulator of the maturation of the myocardium, appears to have a reparative role later in adult life. Changes in TH - thyroid hormone receptor (TR) homeostasis govern the return of the injured myocardium to the fetal phenotype. Accordingly, TH can induce cardiac repair and (or) regeneration by reactivating developmental gene programming. As a proof of concept in humans, TH is found to be an independent determinant of functional recovery and mortality after myocardial infarction. The potential of TH to regenerate and (or) repair the ischemic myocardium is now awaited to be tested in clinical trials.     

Visualization of the intracavitary blood flow in systemic ventricles of Fontan patients by contrast echocardiography using particle image velocimetry

Objectives

Two-dimensional strain echocardiography (2DSE) technique has enabled accurate quantification of regional myocardial function. This experimental study was aimed to investigate the value of 2DSE in detection of segmental regional myocardial dysfunction induced by fibrosis following myocardial infarction in a small animal (rat) model.

Methods

A rat model of myocardial infarction was established by ligation of the proximal left anterior descending coronary artery in 17 SD rats. Regional myocardial function was detected by 2DSE at baseline and 4-weeks post-infarction, including end-systolic radial strain and strain rate (SR and SrR) and end-systolic circumferential strain and strain rate (SC and SrC) of each of six segments at papillary level. According to the size of scar found by histologic Masson staining, the optimal cutoff points of parameters for detecting scar area were analyzed and the sensitivity and specificity of every parameter to detect myocardial scar were obtained using ROC.

Results

(1) Comparing with parameters measured at baseline, there were significant decreases in SR, SrR, SC and SrC of each segment at 4 weeks post-infarction, with the worst in the infarct area (32.90 ± 8.79 vs 11.18 ± 3.89, 6.28 ± 1.35 vs 3.18 ± 0.47, -14.46 ± 2.21 vs -6.30 ± 2.17 and 4.93 ± 0.95 vs 2.59 ± 1.16, respectively) (all P < 0.05). (2)By 4 weeks, the myocardium of infarct area (anteroseptum, anterior and anterolateral) had fibrosis (31.33 ± 9.89, 73.42 ± 13.21 and 13.99 ± 3.24%, respectively) with minimal fibrosis in inferoseptal segment (0.32 ± 0.19%), no fibrosis was found in the inferior and inferolateral segments. (3)Significant negative correlations were found between the size of segmental scar and 2DSE parameters (r-value -0.61 ~ -0.80, all P < 0.01) with the strongest correlation in SR. SR less than 10% has 84% sensitivity and 98% specificity for detecting segments of scar area greater than 30% with AUC = 0.97.

Conclusions

2DSE is able to assess regional myocardial dysfunction in a rat model of myocardial infarction and has high accuracy in detecting infarct segments with scar area greater than 30%.     

Carnitine and acylcarnitine profiles in dried blood spots of patients with acute myocardial infarction

Earlier studies have suggested an important role of carnitine pathway in cardiovascular pathology. However, the redistribution of carnitine and acylcarnitine pools, as a result of altered carnitine metabolism, is not clearly known in patients with acute myocardial infarction (AMI). We compared the carnitine and acylcarnitine profiles of 65 AMI patients, including 26 ST-elevated myocardial infarction (STEMI) and 39 non-ST-elevated myocardial infarction (NSTEMI), 28 patients with chest pain and 154 normal controls. The levels of carnitine and acylcarnitines in the blood spots were determined using LC-MS/MS. Total and free carnitine levels were significantly higher in all the patient groups in the following order: STEMI > NSTEMI > chest pain. The levels of short- and medium-chain acylcarnitines were significantly higher in patient groups. Among the long-chain acylcarnitines, C14:2 and C16:1 levels were significantly increased in STEMI and NSTEMI. The ratio of free carnitine to short-chain or medium-chain acylcarnitines was significantly decreased in STEMI, NSTEMI and chest pain patients however a significant increase was observed in the ratio of carnitine to long-chain acylcarnitines in all the patient groups as compared to normal controls. In conclusion, alterations in carnitine and acylcarnitine levels in the blood of AMI patients indicate the possibility of impaired carnitine homeostasis in ischemic myocardium. The clinical implications of these findings for the risk screening or diagnosis and prognosis of AMI require additional follow-up studies on large number of patients. We also suggest that a dual-marker strategy using carnitine (longer plasma half-life) in combination with troponin (shorter plasma half-life) could be a more promising biomarker strategy in risk stratification of patients.     

Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism

Objective Physical activity has been shown to improve cardiovascular function and to be beneficial to type 2 diabetic patients. However, the effects of aerobic exercise (AE) on myocardial ischemia/reperfusion (MI/R) are largely unclear. Therefore, the aims of the present study were to determine whether long-term AE can protect the heart against I/R injury, and if so, to investigate the underlying mechanism. Methods Adult male Sprague–Dawley rats were randomly subjected to 8 weeks of either sedentary or free-loading swimming exercise (3 h/day, 5 d/week). Then the animals were subjected to 30 min MI followed by 4 h R. Arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the whole MI/R procedure. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (TUNEL analysis) were determined in a blinded manner. Results MI/R caused significant cardiac dysfunction and myocardial apoptosis (strong TUNEL-positive staining). Compared with sedentary group, rats subjected to 8 weeks of AE showed protection against MI/R as evidenced by reduced myocardial infarction (26.8 ± 1.5% vs. 35.3 ± 2.4%, n = 8, P < 0.05), inhibited cardiomyocyte apoptosis (decreased apoptotic index (12.4 ± 1.1% vs. 21.0 ± 1.7%, n = 8, P < 0.01) and decreased myocardial caspase-3 activity), decreased plasma CK and LDH activities and improved recovery of cardiac systolic/diastolic function (including LVSP and ±LVdP/dt) at the end of R. Moreover, exercise resulted in 1.7-fold, 2.5-fold and 2.5-fold increases in Akt expression, Akt phosphorylation and glycogen synthase kinase-3β phosphorylation in I/R myocardium, respectively (n = 3, all P < 0.05). More importantly, treatment with wortmannin, a PI3 kinase inhibitor, 15 min before R not only significantly blocked Akt phosphorylation (P < 0.05) in exercise rats, but also abolished long-term AE-induced cardioprotection for the I/R heart as manifested by increased apoptosis and myocardial infarction, and reduced cardiac function. Conclusion Long-term AE exerts cardioprotective effect against MI/R injury, including anti-cardiomyocyte apoptosis, which is at least partly via PI3 kinase-dependent and Akt-mediated mechanism.     

iPSC‐derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium

We investigated global and regional effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)‐derived mesenchymal stem cells (iMSCs) in infarcted myocardium. Acute myocardial infarction (MI) was induced by ligation of left coronary artery of severe combined immunodeficient mice before 2 × 10⁵ iMSCs or cell‐free saline were injected into peri‐infarcted anterior free wall. Sham‐operated animals received no injection. Global and regional myocardial function was assessed serially at 1‐week and 8‐week by segmental strain analysis by using two dimensional (2D) speckle tracking echocardiography. Early myocardial remodelling was observed at 1‐week and persisted to 8‐week with global contractility of ejection fraction and fractional area change in saline‐ (32.96 ± 14.23%; 21.50 ± 10.07%) and iMSC‐injected (32.95 ± 10.31%; 21.00 ± 7.11%) groups significantly depressed as compared to sham control (51.17 ± 11.69%, P < 0.05; 34.86 ± 9.82%, P < 0.05). However, myocardial dilatation was observed in saline‐injected animals (4.40 ± 0.62 mm, P < 0.05), but not iMSCs (4.29 ± 0.57 mm), when compared to sham control (3.74 ± 0.32 mm). Furthermore, strain analysis showed significant improved basal anterior wall strain (28.86 ± 8.16%, P < 0.05) in the iMSC group, but not saline‐injected (15.81 ± 13.92%), when compared to sham control (22.18 ± 4.13%). This was corroborated by multi‐segments deterioration of radial strain only in saline‐injected (21.50 ± 5.31%, P < 0.05), but not iMSC (25.67 ± 12.53%), when compared to sham control (34.88 ± 5.77%). Improvements of the myocardial strain coincided with the presence of interconnecting telocytes in interstitial space of the infarcted anterior segment of the heart. Our results show that localized injection of iMSCs alleviates ventricular remodelling, sustains global and regional myocardial strain by paracrine‐driven effect on neoangiogenesis and myocardial deformation/compliance via parenchymal and interstitial cell interactions in the infarcted myocardium.     

New,simple and cheap alternative to troponin test for diagnosis of acute myocardial infarction

Acute myocardial infarction (AMI) is often a fatal disorder in humans seen throughout the world. It was earlier diagnosed with some serum enzymes like aspartate transaminase, creatine phosphokinase and its isoenzyme CPK-MB and lactate dehydrogenase which were shown to be increased in AMI. However, in the last few years importance has been given to measuring serum troponins released from the injured myocardium to confirm an AMI. Troponin estimation involves immunological technique, which is expensive with other associated problems like shelf life of reagents, number of samples to be analysed and availability of the kit itself, used for estimation. Under these circumstances the present work involves the measurement of total salt soluble proteins which are proteins associated with troponins also released from myocardium of a patient with AMI. This new test overrules all the disadvantages of the troponin test but seems equally viable and useful for diagnosis of AMI.     

心肌带收缩率与急性心肌梗死患者左心室收缩功能关系

目的:急性前壁心肌梗死明显影响室间隔收缩率和左心室射血分数(left ventricular ejection fraction LVEF)。本文旨在探讨心肌带降段及升段收缩率与急性前壁心肌梗死患者LVEF的相关性。方法:收集2015年4月-2017年2月在心内科住院的急性前壁心肌梗死患者36例,正常对照组患者39例。所有患者取左心室长轴M型超声心动图,测量室间隔收缩率、升段收缩率及降段收缩率。心肌梗死左心室射血分数采用双平面Simpson's法计算。结果:与正常对照组相比,心肌梗死组患者舒张末期心肌带升段厚度没有统计学差异(P=0.69),收缩末期升段厚度(P=0.014)更薄、升段收缩率(P0.01)明显降低;心肌梗死组舒张末期降段厚度(P0.01)更薄、收缩末期降段厚度(P0.01)更薄、降段收缩率(P0.01)明显降低;心肌梗死组左心室射血分数与降段收缩率(r~2=0.13,P=0.026)、室间隔增厚率(r~2=0.19,P0.01)呈正相关,与升段收缩率没有相关性(P0.05)。正常对照组左心室射血分数与室间隔增厚率、降段增厚率及升段增厚率无相关性。经过相关分析,筛选出与心肌梗死LVEF的相关因素,进一步经逐步回归分析,得多元线性回归方程为LVEF=48.206+18.914*LVDD(cm)-25.414*LVSD(cm)。结论:急性前壁心肌梗死室间隔降段收缩率明显受损,与左心室射血分数降低有关。多元线性回归方程可估算前壁心肌梗死LVEF。     

3-D MRI assessment of regional left ventricular systolic wall stress in patients with reperfused MI

The goal of this study was to assess the regional variations of end-systolic wall stress in patients with reperfused Q wave acute myocardial infarction (AMI), with the use of a three-dimensional (3-D) approach. Fifteen normal volunteers and fifty patients with reperfused AMI underwent cardiac MRI that used a short-axis fast-gradient-echo sequence. The end-systolic wall stress was calculated with the use of the Grossman formula with the radius and the wall thickness defined with a 3-D approach using the tridimensional curvature. The mean wall stress was significantly increased at each level of the short-axis plane only in patients with anterior AMI. When calculated at a regional level in patients with anterior AMI, wall stress significantly increased in anterior sector as well as normal sector. In patients with inferior AMI, wall stress significantly increased only in inferior and lateral sectors. In conclusion, the quantification of regional wall stress by cardiac MRI is better with the 3D approach than other methods for precise evaluation in patients with AMI. Despite early reperfusion, the wall stress remained high in patients with anterior AMI.     

Relative hyperglycemia is associated with complications following an acute myocardial infarction: a post-hoc analysis of HI-5 data

Background

Hyperglycemia is associated with increased morbidity and mortality in patients with an acute myocardial infarction (AMI). We evaluated whether complications after AMI are associated with absolute or relative glycemia.

Methods

A total of 192 patients with AMI were randomized to intensive or conventional insulin therapy. Absolute glycemia was defined as mean blood glucose level (BGL) during the first 24 h following randomization. Relative glycemia was defined by the stress hyperglycaemia ratio (SHR), calculated as mean BGL divided by average glucose concentration over the prior 3 months estimated from glycosylated haemoglobin. The primary endpoint was a “complicated AMI”, defined as an AMI complicated by death, congestive cardiac failure, arrhythmia, cardiac arrest, reinfarction, cardiogenic shock, inotrope use or emergency revascularization.

Results

There was not a significant association between mean BGL and complicated AMI (odds ratio (OR) 1.05 per mmol/L glucose increment, 95% confidence intervals (CI) 0.93–1.19). In contrast, SHR was positively associated with a complicated myocardial infarction (OR 1.22 per 0.1 SHR increment, 95% CI 1.06–1.42), and individual complications of death (OR 1.55, 95% CI 1.14–2.11), congestive cardiac failure (OR 1.27, 95% CI 1.05–1.54), arrhythmia (OR 1.31, 95% CI 1.12–1.54) and cardiogenic shock (OR 1.42, 95% CI 1.03–1.97). The relationship between SHR and a complicated AMI was independent of diabetic status, intensive insulin therapy, sex and hypoglycemia.

Conclusions

Relative, but not absolute, glycemia during insulin treatment is independently associated with complications after an AMI. Future studies should investigate whether basing therapeutic glycaemic targets on relative glycemia improves patient outcomes.

     

Coronary microcirculatory dysfunction is associated with left ventricular dysfunction during follow-up after STEMI

Background

Coronary microvascular resistance is increased after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), which may be related in part to changed left ventricular (LV) dynamics. Therefore we studied the coronary microcirculation in relation to systolic and diastolic LV function after STEMI.

Methods

The study cohort consisted of 12 consecutive patients, all treated with primary PCI for a first anterior wall STEMI. At 4 months, we assessed pressure-volume loops. Subsequently, we measured intracoronary pressure and flow velocity and calculated coronary microvascular resistance. Infarct size and LV mass were assessed using magnetic resonance imaging.

Results

Patients with an impaired systolic LV function due to a larger myocardial infarction showed a higher baseline average peak flow velocity (APV) than the other patients (26?±?7 versus 17?±?5 cm/s, p?=?0.003, respectively), and showed an impaired variable microvascular resistance index (2.1?±?1.0 versus 4.1?±?1.3 mmHg?cm^?1?s^?1, p?=?0.003, respectively). Impaired diastolic relaxation time was inversely correlated with hyperaemic APV (r?=??0.56, p?=?0.003) and positively correlated with hyperaemic microvascular resistance (r?=?0.48, p?=?0.01). LV dilatation was associated with a reduced variable microvascular resistance index (r?=?0.78, p?=?0.006).

Conclusion

A larger anterior myocardial infarction results in impaired LV performance associated with reduced coronary microvascular resistance variability, in particular due to higher coronary blood flow at baseline in these compromised left ventricles.     

Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 x 10(5) cells in 20 microl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 +/- 2% vs. 36 +/- 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 +/- 3% vs. 16 +/- 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 +/- 0.3% of injected cells) expressed von Willebrand factor (16.9 +/- 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.