Application of the fourth universal definition of myocardial infarction in clinical practice

Abstract

Purpose: The Fourth Universal Definition of Myocardial Infarction (MI) has highlighted the different pathophysiological mechanisms that may lead to ischaemic and non-ischaemic myocardial injury and has emphasised that the diagnosis of myocardial infarction requires the presence of acute myocardial ischaemia in the setting of acute myocardial injury. This case based review intends to illustrate basic principles on how to apply this new, revised definition in clinical practice.

Methods and Results: The distinction between different types of MIs (type 1 or type 2) and the delineation of MI from acute non-ischaemic myocardial injury may be challenging in individual patients, which is illustrated by presenting and discussing real-life routine cases.

Conclusions: Type 1?MI is a consequence of coronary plaque rupture or erosion with intracoronary thrombus formation that is usually apparent on coronary angiography. Plausible triggering mechanisms causing myocardial oxygen supply/demand mismatch must be identified for the diagnosis of type 2?MI and its treatment should focus initially on management of the underlying disease attributable to acute myocardial ischaemia.     

Postnatal differentiation of ventricular myocardial cells of the opossum (Didelphis virginiana Kerr) and T-tubule formation

Summary Cardiac muscle cells in the right ventricle of the postnatal opposum were studied ultrastructurally, with particular attention to the developmental stage of T-tubule formation. Animals ranging from 5.5cm (day 29 of postnatal life) to 41 cm (young adult) in body length were used. Typical T-tubules were first recognized in a few myocardial cells of the 7.5cm (day 43) opossum. T-tubules increased in number as cardiac muscle cells continued to differentiate until 22cm in body length (about 105 days after birth). At this stage of development most of the T-tubules were completely established. The general mode of differentiation and development of cardiac muscle cells appeared essentially the same as in other mammals.This work was supported in part by a grant-in-aid to R.H. form the Ministry of Education of Japan for special project research on the cardiovascular system     

Hospital cardiovascular deaths and total distribution of deaths in 180 consecutive months with different cosmic physical activity: a correlative study (1974–1988)

The dynamics of total hospital deaths from different kinds of cardiovascular diseases in one 1000-bed hospital were compared with 10 monthly cosmic/solar and geomagnetic physical activity parameters. Data used were of 180 consecutive months; 15601 deaths including 5667 from cardiovascular diseases were included in this study. It was concluded that the number of monthly hospital deaths shows a highly significant correlation with monthly solar physical activity.     

Regulation of alternative macrophage activation by MSCs derived hypoxic conditioned medium,via the TGF-β1/Smad3 pathway

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.      

B型钠尿肽对急性心肌缺血损伤发挥保护作用的机制

本研究旨在研究B型钠尿肽(brain natriuretic peptide, BNP)对异丙肾上腺素(isoproterenol, ISO)诱导的急性心肌缺血(acute myocardial ischemia, AMI)相关损伤的保护作用。将大鼠随机分作5组:对照组、ISO处理组、ISO+普萘洛尔(5 mg/kg)处理组、ISO+BNP (5 mg/kg)和ISO+BNP (10 mg/kg)处理组。再将4个给药组中的大鼠连续2 d皮下注射ISO。通过心电图(ECG)记录ST段数据;ELISA检测血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6 (IL-6)和IL-1β的表达水平;接着使用Western blotting对Bax-2、Bcl-2、PI3K、Akt、GSK-3β、MDA5和SOD1蛋白表达水平进行检测,并测定PI3K、Akt和GSK-3β的磷酸化。实验结果显示,BNP (5 mg/kg, 10 mg/kg)可降低血清中MDA和CK的表达水平以及SOD和LDH的蛋白活性;经BNP预处理显著降低了促炎因子IL-1β、IL-6和TNF-α的表达水平;同时BNP也降低了ST段抬高。此外,BNP改善了ISO诱导的大鼠中SOD1、MDA5、Bax-2、Bcl-2、p-PI3K、p-Akt和p-GSK-3β的表达。综上所述,通过调节PI3K/Akt/GSK-3β信号传导途径,BNP保护大鼠免受AMI损伤。     

MR image analysis of ex-vivo mouse model of heart ischemia

IntroductionMyocardial infarction is one of the major causes of death and disability. Various diagnostic modalities used to investigate cardiac ischaemia. Advances in Magnetic Resonance Imaging technology has opened up new horizons for investigating the cardiac function and quantifying any pathology that may be present.AimsThe present study was designed to quantify the cardiac area at risk and infarction reperfusion areas using the mismatch of iron oxide contrast and gadolinium (Gd) contrast imaging (MRIs) and to test if a combination of T1, T2, and iron oxide T2* contrasts will distinguish the infarction and AAR zones.MethodsA well-established mouse model was used to induced cardiac ischaemia and reperfusion. Six mice models’ hearts were harvested and processed according to various protocols. MI was induced through ligation technique for five mice, and one was kept as normal control. MR imaging and Reperfusion were performed using a Three-dimensional gradient-echo fast low angle shot (3DFLASH) and three-dimensional multi-slice multi-echo sequence (3DMSME). Generation of T1 and T2 maps, image post-processing including segmentation and mismatch measurement and drawing of the area of interest.ResultsThe edematous myocardium had significant high signal intensity in 3DMSME with variable echo time (14, 28, 42 ms). The combination of 3DFLASH and 3DMSME at an echo time of 42 ms was statistically significant, detecting the AAR more accurately. Both T1 and T2 sequences had the potential to determine the AAR zone. The infarct area has significantly high signal intensity compared to normal areas (p = 0.04 for the T1 map and p = 0.01 for the T2 map).ConclusionsThe study demonstrated that Cardiac MRI was a valuable technology to investigate infarct areas and zones that are at risk.     

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked. In contrast, chronic instrumentation allows for measurement of cardiopulmonary function in the awake state, so that measurements can be obtained under quiet resting conditions, without the effects of anesthesia and acute surgical trauma. Furthermore, when animals are properly trained, measurements can also be obtained during graded treadmill exercise.Flow probes are placed around the aorta or pulmonary artery for measurement of cardiac output and around the left anterior descending coronary artery for measurement of coronary blood flow. Fluid-filled catheters are implanted in the aorta, pulmonary artery, left atrium, left ventricle and right ventricle for pressure measurement and blood sampling. In addition, a 20 G catheter is positioned in the anterior interventricular vein to allow coronary venous blood sampling.After a week of recovery, swine are placed on a motor-driven treadmill, the catheters are connected to pressure and flow meters, and swine are subjected to a five-stage progressive exercise protocol, with each stage lasting 3 min. Hemodynamic signals are continuously recorded and blood samples are taken during the last 30 sec of each exercise stage.The major advantage of studying chronically instrumented animals is that it allows serial assessment of cardiopulmonary function, not only at rest but also during physical stress such as exercise. Moreover, cardiopulmonary function can be assessed repeatedly during disease development and during chronic treatment, thereby increasing statistical power and hence limiting the number of animals required for a study.     

The protective effect of peony extract on acute myocardial infarction in rats

To investigate the protective effects, and the mechanisms involved, of an extract of the medicinal herb radix paeoniae rubra (PE) on cardiovascular disease, acute myocardial infarction (AMI) was induced by ligation of the left coronary artery in Sprague Dawley rats. Animals were randomly divided into six groups: control, sham-operated, AMI, AMI + PE low dose, AMI + PE high dose, and AMI + positive control. Myocardial enzymes, cytokines, oxidative stress, blood coagulation times, a marker for early stage apoptosis, caspase-3 activity, and expression levels of bax, bcl-2 and fas in isolated primary cardiomyocytes were examined. In contrast with control and sham groups, significant increases in the following parameters were measured in the blood of AMI group animals: activities of cardiac enzymes including glutamic oxaloacetic transaminase, creatine kinase, creatine kinase-MB, lactate dehydrogenase, α-hydroxybutyric dehydrogenase, and levels of IL-10, TNFα, and lipid peroxidation. Under the same conditions, superoxide dismutase activity, thrombin time and activated partial thromboplastin time decreased significantly. PE showed a dose-dependent protection against AMI-induced alterations in cardiac enzymes, cytokines, oxidative stress, and coagulation. In AMI cardiomyocytes, compared with control and sham groups, the left ventricular end-diastolic pressure, early stage apoptosis, caspase-3 activity and expression levels of bax, bcl-2 and fas significantly increased, while the ratio bcl-2/bax decreased. PE showed dose-dependent protection. These results suggest that PE is an effective agent for protecting against AMI; possible mechanisms may include the regulation of cardiac enzymes, cytokines, oxidative stress, coagulation and apoptosis.     

Relationship between suicide and myocardial infarction with regard to changing physical environmental conditions

In recent years, the possible association of changes in mortality from cardiovascular disease and myocardial infarction (MI) and deaths related to violence and the suicide rate has been repeatedly discussed. This study examined the relationship between cosmic physical changes (solar, geomagnetic and other space activity parameters) and changes in the total number of in-hospital and MI-related deaths and deaths from suicide to determine if a relationship exists between the distribution of total and MI-related deaths with suicide over time; some differences in the serotonergic mechanisms involved in the pathogenesis of MI and suicide were also taken into account. All suicides (n=2359) registered in the State of Israel from 1981 to 1989 (108 months) were analysed and compared with the total number of deaths (n=15601) and deaths from MI (n=1573) in a large university hospital over 180 months (1974–1989). The following were the main features of the Results. (1) Monthly suicide rate was correlated with space proton flux (r=0.42,P=0.0001) and with geomagnetic activity (r=–0.22,P=0.03). (2) Total hospital and MI-related deaths were correlated with solar activity parameters (r=0.35,P<0.001) and radiowave propagation (r=0.52-0.44,P<0.001), an with proton flux (r=–0.3 to –0.26,P<0.01). (3) Monthly suicide distribution over 108 months was correlated with MI (r=–0.33,P=0.0005) and total hospital mortality (r=–0.22,P=0.024). (4) Gender differences were prominent. We conclude that the monthly distributions of suicides and deaths from MI are adversely related to many environmental physical parameters and negatively correlated with each other.     

Expression of uncoupling protein 3 in mitochondria protects against stress-induced myocardial injury: a proteomic study

It has been confirmed that stress plays an important role in the induction and development of cardiovascular diseases, but its mechanism and molecular basis remain unknown. In the present study, a myocardial injury model induced by restraint stress was established in rat. To screen for the related proteins involved in stress-induced myocardial injury, proteomic techniques based on 2-DE and mass spectrometry were used. In our results, ten proteins were found to be altered. The expression of eight of these proteins was increased after restraint stress, including cardiac myosin heavy chain, dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial aldehyde dehydrogenase, H⁺-transporting ATP synthase, albumin, and apolipoprotein A-I precursor. The expression of uncoupling protein 3 (UCP3) and mitochondrial aconitase was decreased. Most of the proteins were related to energy metabolism. Further research indicated that UCP3 may mediate the myocardial cell response induced by restraint stress.