Degree Of Myocardial Infarction Research Articles

Post-mortem evaluation of the pathological degree of myocardial infarction by Fourier transform infrared microspectroscopy

In clinical and forensic investigations, accurate post-mortem diagnosis of the pathological degree of myocardial infarction (MI) is critical. However, because of the observer variability, the diagnosis cannot be made objectively. Many studies have shown that Fourier transform infrared (FTIR) microspectroscopy is non-invasive, observer-independent, and label-free when analyzing biological tissues. In this study, we used FTIR microspectroscopy in combination with intelligent algorithms to identify the pathological phases in human infarcted cardiac tissues, including ischemia, necrotic, granulation, and fibrotic stages. First, a comparison of infrared spectra corresponding to infarcted tissue pathological categories revealed various spectral properties. The results of unsupervised principal component analysis (PCA) revealed a clear distinction between these four pathological stages and the normal stage. Then, to identify these five stages, an automatic artificial neural network (ANN) classifier was effectively created. Finally, two-dimensional pseudo-color images of two infarcted cardiac tissue sections visualized via the ANN classifier showed great agreement with their histological images. These findings demonstrate that FTIR microspectroscopy has the potential for the post-mortem evaluation of the pathological degree of MI.

Mechanism of curcumin against myocardial ischaemia-reperfusion injury based on the P13K/Akt/mTOR signalling pathway.

To investigate the pharmacodynamic mechanism of curcumin against myocardial ischaemia-reperfusion injury by regulating the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/rapamycin target protein (mTOR) signalling pathway. The left anterior descending coronary artery was ligated for 30 min and reperfused for 3 h to establish an ischaemia-reperfusion injury model. The electrocardiogram (ECG) detection of rats was performed, and the degree of myocardial infarction was determined by 2,3,5-triphenyltetrazolium chloride staining. The expression levels of serum creatine kinase isoenzyme (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO) and other related indicators were detected. The protein expressions of mTOR, phosphorylated (p)-mTOR, AKT and p-AKT were detected by Western blotting, whereas the expressions of Bcl-2 and Bax were detected by real-time polymerase chain reaction. The results showed that compared with the model group, curcumin could improve the ECG findings, reduce the scope of myocardial infarction, reduce the expression levels of CK-MB, LDH, AST, MDA, NO and increase those of SOD and GSH. Curcumin can also down-regulate the expression of Bax and up-regulate the protein levels of Bcl2, p-mTOR and p-AKT (p < 0.05 or p < 0.01). This study shows that curcumin has a significant protective effect on myocardial ischaemia-reperfusion, and its mechanism may be related to the activation of PI3K/AKT/mTOR signalling pathway and inhibition of inflammation, apoptosis and oxidative stress.

Comparison of Left Ventricular Global Strain in Anterior and Non-anterior Wall Myocardial Infarction With CMR Tissue Tracking.

Left ventricular (LV) myocardial dysfunction occurs after myocardial infarction (MI) is associated with the location, infarct size, and transmurality degrees of MI. The myocardial strain is a sensitive index used for the quantification of myocardium dysfunction. This study used Tissue-Tracking to evaluate whether the different location of MI would result in different myocardial dysfunction. One hundred patients diagnosed with MI who underwent cardiovascular magnetic resonance examination were included. The tissue-tracking indices, LV global radial strain (GRS), global circumferential strain (GCS), global longitudinal strain (GLS), and the infarct size (IS,% of LV mass) were quantified. There were 42 cases of anterior wall MI (AWMI) and 58 cases of non-anterior wall MI (NAWMI). The GCS of AWMI was significantly lower than that of NAWMI (P = 0.036). In the same level of infarct size, the myocardial strain of AWMI was not significantly different from NAWMI group (P > 0.05). The GRS and GCS were significantly different between transmurality > 50% group with transmurality ≤ 50% group (P < 0.05). The present study demonstrated that LV MI is associated with reduced myocardial strain, and the infarct size and degrees of transmurality were both related to the decline of myocardial strain in patients with MI.

Prevalence of myocardial viability and ischemic burden in chronic total occluded coronary artery disease

Abstract Aims We assessed the viable myocardium status and investigated the relationship between collaterals with the ischemia burden and myocardial viability utilizing cardiac magnetic resonance imaging (CMR) and adenosine stress single-photon emission computed tomography (SPECT). Methods and results 150 consecutive patients with at least one native CTO artery, as confirmed by coronary arteriography or coronary CT angiography, were prospectively recruited. SPECT examination was accepted by only 50 patients while declined by the other 100 patients for reasons such as financial problems. Of all segments in the 173 CTO artery territories, only 10.4% exhibited transmural myocardial infarction and 60.2% showed no late gadolinium enhancement. Among 50 patients who completed SPECT examination, 36 patients showed inducible perfusion defect in CTO territory, and the proportion of the ischemic area of 42% patients was over 10%. Conclusion Most patients with CTO had different degrees of myocardial infarction detected by CMR, but only a minority of them showed transmural infarction and cardiac function in patients with transmural infarction declined compared to those without transmural infarction. Approximately half of CTO patients exhibited inducible ischemia in CTO territory. Based on this, a large proportion of patients potentially benefit from CTO-PCI. Figure 1. Relationship between WMSI, LVE Funding Acknowledgement Type of funding source: Other. Main funding source(s): Beijing Municipal Education Commission Science and Technology Plan for 2020, Capital Health Development Research Project (no. 2018-2-2063)

Cardiovascular Effects of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibition in the Setting of Ischemia/Reperfusion Injury

Background and Hypothesis: Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study was designed to test the hypothesis that SGLT2i improves cardiac function and mitigates myocardial infarct size following regional myocardial ischemia and reperfusion injury. &#x0D; Experimental Design: Lean domestic swine received placebo (n=6) or canagliflozin (n=6; 300 mg PO) 24 hours prior to and the morning of an experiment. Hemodynamics, left ventricular pressure and volume were measured in open chest, swine at baseline, during a 60 min coronary occlusion, and during a 2-hour reperfusion period. The degree of myocardial infarction was assessed by staining with 1% tetrazolium. &#x0D; Results: At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P &lt; 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P &lt; 0.01). This increase in ventricular filling was associated with significant increases in stroke volume (P &lt; 0.05) and stroke work (P &lt; 0.05) relative to untreated controls swine during ischemia. SGLT2i decreased infarct size from 9.4 [Symbol] 2.1% in control swine to 3.1 [Symbol] 0.98% in SGLT2i treated swine. &#x0D; Conclusion: SGLT2 inhibitors significantly improve cardiac contractile function and mitigate myocardial infarct size following regional myocardial ischemia and reperfusion injury in domestic swine.

Hypertension Enhances Advanced Atherosclerosis and Induces Cardiac Death in Watanabe Heritable Hyperlipidemic Rabbits

Hypertension is a major risk factor for the development of atherosclerosis. Cardiovascular risk has been reported to be significantly increased in hyperlipidemic patients with hypertension. However, it is not clear whether hypertension can directly destabilize plaques, thereby enhancing cardiovascular events. To examine whether hypertension enhances the development of atherosclerosis and increases plaque vulnerability, we generated hypertensive Watanabe heritable hyperlipidemic (WHHL) rabbits by surgical removal of one kidney and partial ligation of the other renal artery and compared the nature of aortic and coronary atherosclerosis in hypertensive WHHL rabbits with normotensive WHHL rabbits. All hypertensive WHHL rabbits died from 34 to 56 weeks after surgery, whereas no normotensive WHHL rabbits died. Pathologic examinations revealed that hypertensive WHHL rabbits showed different degrees of myocardial infarction caused by severe coronary stenosis along with myocardial hypertrophy. Furthermore, aortic lesions in hypertensive WHHL rabbits exhibited a higher frequency of intraplaque hemorrhage and vulnerable plaques than those in normotensive WHHL rabbits. These results indicate that hypertension induced by the surgical removal of one kidney and partial ligation of the other renal artery method in WHHL rabbits may not only enhance the development of atherosclerosis but also destabilize the plaques, increasing cardiac death.

Protective effect of scutellarin on myocardial infarction induced by isoprenaline in rats.

Objective(s):Scutellarin (Scu) is the main effective constituent of Erigeron breviscapus which has anti-oxidant, anti-apoptotic, anti-inflammatory and other therapeutic properties. The purpose of this study was to investigate the protective effect of Scu on myocardial infarction (MI) induced by isoprenaline (ISO).Materials and Methods:The rats were subcutaneously injected with ISO (45 mg/kg) on the first day, then single tail-intravenously injected with different doses of Scu (10 mg/kg, 20 mg/kg, 40 mg/kg) for 7 consecutive days. The protective effect of Scu on ISO-induced MI was evaluated by measuring markers of heart injury in serum, levels of lipid peroxidation, and antioxidants in heart tissue, observing pathological changes of tissue, and detecting quantified expression of apoptotic-related family members and inflammation.Results:Compared with the model group, the concentration of troponin T (CTn-T) and troponin I (CTn-I), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the serum all decreased in the Scu high dose group. The activities of superoxide dismutase (SOD), catalase (CAT), and the content of reduced glutathione (GSH) in heart increased, and the content of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) decreased. In addition, the histopathologic aspects showed that pathological heart change was found in the model group, and was reduced to varying degrees in the Scu group. Moreover, the expression of Bax, P53, Caspase3, Caspase9, cytochrome C, NGAL, NFκB, IL-1β and IL-6 in the heart decreased, while the expression of Bcl2 increased.Conclusion:Scu could reduce the degree of MI induced by ISO by improving the antioxidant, anti-apoptotic, and anti-inflammatory capacities of the body.

Dynamic detection of surface blood flow in rat heart and its application in real time identification of myocardial infarction model

Objective: To establish a method for monitoring the surface blood flow in the heart of rats, and to clarify the relationship between the degree of myocardial infarction and the blood perfusion on the surface of the heart, so as to provide a new indicator for the identification of rat myocardial infarction model. Methods: The rats were divided into control group (n=23) and model group (n=107), the rat hearts were scanned by the laser doppler perfusion imager before and after operation respectively, and the data was analyzed to acquire the rate of surface blood flow change of the heart. Myocardial infarction size of model group was detected by NBT. Model group were divided into three subgroups of mild myocardial infarction, moderate myocardial infarction and severe myocardial infarction according to the myocardial infarction size, and an analysis was made on the correlativity between rate of surface blood flow change of the heart and myocardial infarction size. Results: Myocardial infarction size was highly correlated to the rate of surface blood flow change of the heart in model group (r=0.849 6, P<0.000 1). There was no significant correlation between infarction size and heart blood flow in the mild myocardial infarction subgroup (r=-0.133 6, P>0.05), while the correlation in moderate myocardial infarction was significant (r=0.721 7, P<0.000 1), and the highest correlation was shown in severe myocardial infarction subgroup (r=0.910 2, P<0.000 1). Conclusion: The heart surface blood flow has a close relationship with the myocardial infarction size in rat, so the change of heart blood perfusion can beused as an effective reference to establish and identify rat myocardial infarction model.

MiR-539 as akey negative regulator of the MEK pathway in myocardial infarction.

Myocardial infarction is one of the most common causes of death, and the number of individuals at risk is increasing. A rapid and accurate differential diagnosis of myocardial infarction is crucial for timely interventions and for improvement of the prognosis. However, it is difficult to achieve using current methods. To better manage this condition, improved tools for risk prediction, including more accurate biomarkers, are needed. We studied the expression of microRNA-539 (miR-539) and of MEK protein using a rat model of myocardial infarction. The results of our experiments demonstrated an increase in the expression of miR-539 and a decrease in the expression of MEK. Furthermore, we observed that miR-539 inhibited the expression of MEK through targeting of the 3'UTR of MEK; this led not only to suppressed proliferation but also to apoptosis and autophagy of H9C2 cells. Overexpression of miR-539 plays a role in the degree of myocardial infarction. On the basis of our results, we conclude that miR-539 may be apotential therapeutic target for myocardial infarction.

Investigation into the optimal surgical conditions for coronary artery ligation for establishing a myocardial infarction model in mice

In the present study, the left anterior descending coronary arteries of mice under anesthesia were ligated, and the optimal surgical conditions for coronary artery ligation (CAL) in the establishment of a myocardial infarction (MI) mouse model were investigated. All mice that survived were sacrificed seven days subsequent to the successful surgery. Body weight, blood serum and heart tissues were obtained for further analysis or biochemical and histopathological examinations. The survival rate of the mice following the CAL procedure was 70%. The aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations in the serum of the experimental mice were significantly increased compared with those of the control mice, which reflected the enzyme release from the infarcted myocardial cells. Histopathological examination showed different degrees of MI in the heart tissues of the experimental mice. The results indicate that an MI model in mice may be successfully established using CAL under the surgical conditions utilized in the present study. These conditions were cost effective and the results may be replicated by laboratories that are less well-equipped.

Effects of effective components compatibility of aqueous extracts of Salviae Miltiorrhizae and Rhizoma Chuanxiong on rat myocardial ischemia/reperfusion injury

To observe effects of effective components compatibility of aqueous extracts of Salviae Miltiorrhizae and Rhizoma Chuanxiong on myocardial ischemia/reperfusion (I/R) injury in rat. Sprague-Dawley (SD) rats were randomly divided into sham group, model group, Guanxinning injection group and effective components of aqueous extracts from Salviae Miltiorrhizae and Rhizoma Chuanxiong salvianolic low dose group and high dose group, with 10 rats in each group. The myocardial I/R injury model was reproduced by ligation of the left anterior descending artery, and the experimental drugs were injected intravenously via femoral vein at 10 minutes after ligation. 2.88 g/kg Guanxinning injection was given in Guanxinning group, and 2.43 g/kg or 4.86 g/kg effective components of aqueous extracts of Salviae Miltiorrhizae and Rhizoma Chuanxiong salvianolic was given in low dose group and high dose group, respectively, and equal volume of normal saline was given in sham group and model group. The anesthetic rats were sacrificed 40 minutes after ischemia and 120 minutes of reperfusion. Blood samples were collected before rats were sacrificed. The contents of serum troponin T (cTnT) and MB isoenzyme of creatine kinase (CK-MB) were determined, 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)), thromboxane B(2) (TXB(2)) and platelet aggregation rate in blood plasma were assessed, and the degree of myocardial infarction in rats was determined. The myocardial infarction size in combined Salviae Miltiorrhizae and Rhizoma Chuanxiong low dose group and high dose group [(23.0+/-3.8)%, (20.8+/-4.7)%] were lower significantly than that in model group [(29.1+/-3.2)%, P<0.05 and P<0.01], the contents of serum cTnT [(0.78+/-0.29) mg/L, (0.76+/-0.29) mg/L] and CK-MB [(891.5+/-252.5) U/L, (759.5+/-191.3) U/L] were lower significantly than those in model group [(1.04+/-0.14) mg/L, (1 268.2+/-256.5) U/L, all P<0.05]. The level of 6-keto-PGF(1 alpha) was higher significantly in high dose of the combination group than that in model group [(206.7+/-35.6) ng/L vs. (138.6+/-28.9) ng/L, P<0.05], and platelet aggregation rate was inhibited significantly [(49.4+/-9.3)% vs. (77.1+/-16.7)%, P<0.05]. Effective components compatibility of aqueous extracts from Salviae Miltiorrhizae and Rhizoma Chuanxiong may reduce significantly the size of myocardial infarct and blood content of myocardial enzyme CK-MB and cTnT, and increase the ratio of 6-keto-PGF(1 alpha)/TXB(2), thus reducing myocardial I/R injury.

Enhanced activity and subcellular redistribution of myocardial hexokinase after acute myocardial infarction

Background Hexokinase (HK) is known to possess both anti-oxidant and anti-apoptotic properties. This study investigated the behavior of myocardial HK in response to myocardial infarction (MI). Methods Adult male Wistar rats with various degrees of MI after coronary ligation were examined 4 weeks after operation and were divided dichotomously into small and large MI groups. The activity and subcellular distribution of HK in the non-infarcted myocardium were determined. In parallel, myocardial oxidative stress determined using aconitase activity and malondialdehyde content, and left ventricular function using echocardiography were studied. Results In the mitochondria and the cytosol, HK activity was enhanced after MI and paralleled the increases in oxidative stress and left ventricular end-diastolic dimension (LVEDD). The enhancement in HK activity varied between subcellular compartments and resulted in an increase in the ratio of cytosol to whole-cell HK activity, which was proportional to oxidative stress and LVEDD. Conclusions The activities of HK in all subcellular fractions are enhanced in response to MI. However, enhanced proportion of cytosolic HK relative to whole-cell HK activity is associated with higher oxidative stress and LVEDD, suggesting that altered myocardial HK activity and subcellular redistribution might be involved in the pathogenesis of postinfarct heart failure.

Wideband High-Frequency Echocardiography to Evaluate Myocardial Infarct Size

This study was designed to validate the feasibility of wideband high-frequency ultrasound imaging to resolve in vivo the degree, location, and morphologic changes of myocardial infarction (MI) in a rat model. The left anterior descending coronary artery was ligated in the test group (n = 41), and the sham control group did not have ligation (n = 7). The rats were examined with 10- to 22-MHz echocardiography to evaluate the MI size, location, and geometric formation. The endocardial chamber shape was deformed, with enlargement of the anteroposterior dimension and fractional shortening, and was comparable with the degree of MI both in short- and long-axis sections of the left ventricle. Histologic analysis showed remodeling to different extents corresponding to different MI sizes (small, medium, and large). The results suggest that this technique can be used in vivo to evaluate the MI location, size, and morphologic changes corresponding to the extent of the injury.

Influence of gender on the response to hemodynamic overload after myocardial infarction.

After myocardial infarction (MI), the left ventricle (LV) undergoes ventricular remodeling characterized by progressive global dilation, infarct expansion, and compensatory hypertrophy of the noninfarcted myocardium. Little attention has been given to the response of remodeling myocardium to additional hemodynamic overload. Studies have indicated that gender may influence remodeling and the response to both MI and hemodynamic overload. We therefore determined 1) structural and function consequences of superimposing hemodynamic overload (systemic hypertension) on remodeling myocardium after a MI and 2) the potential influence of gender on this remodeling response. Male and female Dahl salt-sensitive and salt-resistant rats underwent coronary ligation, resulting in similar degrees of MI. One week post-MI, all rats were placed on a high-salt diet. Four groups were then studied 4 wk after initiation of high-salt feeding: MI female, MI female + hypertension, MI male, and MI male + hypertension. Hypertension-induced pressure overload resulted in additional comparable degrees of myocardial hypertrophy in both females and males. In females, hypertension post-MI resulted in concentric hypertrophy with no additional cavity dilation and no measurable scar thinning. In contrast, in males, hypertension post-MI resulted in eccentric hypertrophy, further LV cavity dilation, and scar thinning. Physiologically, concentric hypertrophy in post-MI hypertensive females resulted in elevated contractile function, whereas eccentrically hypertrophied males had no such increase. Female gender influences favorably the remodeling and physiological response to hemodynamic overload after large MI.

THERAPEUTIC RAMIFICATIONS OF THE INTERACTION OF COMPLEMENT, GRANULOCYTES, AND PLATELETS IN THE PRODUCTION OF ACUTE LUNG INJURY*

Evidence is reviewed that activation of complement through its ability to cause adhesion of granulocytes to the pulmonary endothelium (margination) and aggregation and embolization of these cells to the lung microvasculature is an important cause of pulmonary injury. Agents capable of diminishing such stimulated adhesiveness might be rational therapeutic adjuncts in vascular-damaging syndromes and are being investigated. To date, corticosteroids, such as methylprednisolone (in enormous doses), and certain nonsteroidal anti-inflammatory drugs, such as ibuprofen, have been shown to diminish granulocyte stickiness in vitro and diminish complement-mediated tissue damage in vivo. Moreover, platelets amplify complement/granulocyte-induced endothelial damage by releasing serotonin, which, in turn, potentiates granulocyte adhesion to endothelium. This potentiation is abrogated by the serotonin antagonists imiprimine and methysergide. Since these diverse agents inhibit granulocyte-adhesion phenomena by different mechanisms, they might predictably be synergistic in their beneficial effect. This prediction is validated for methylprednisolone and ibuprofen, for which we report a threefold synergism in preventing complement-mediated granulocyte aggregation in vitro. Preliminary studies indicate utility of this synergism in vivo as well, in that the degree of myocardial infarction [a complement-activating phenomenon) is diminished in coronary-ligated animals in which rather small doses of the two drugs administered together.