Damage In Acute Myocardial Infarction Research Articles

Novel Role for Cardiolipin as a Target of Therapy to Mitigate Myocardial Injury Caused by Venoarterial Extracorporeal Membrane Oxygenation.

Cardiolipin is a mitochondrial-specific phospholipid that maintains integrity of the electron transport chain (ETC) and plays a central role in myocardial ischemia/reperfusion injury. Tafazzin is an enzyme that is required for cardiolipin maturation. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use to provide hemodynamic support for acute myocardial infarction has grown exponentially, is associated with poor outcomes, and is under active clinical investigation, yet the mechanistic effect of VA-ECMO on myocardial damage in acute myocardial infarction remains poorly understood. We hypothesized that VA-ECMO acutely depletes myocardial cardiolipin and exacerbates myocardial injury in acute myocardial infarction. We examined cardiolipin and tafazzin levels in human subjects with heart failure and healthy swine exposed to VA-ECMO and used a swine model of closed-chest myocardial ischemia/reperfusion injury to evaluate the effect of VA-ECMO on cardiolipin expression, myocardial injury, and mitochondrial function. Cardiolipin and tafazzin levels are significantly reduced in the left ventricles of individuals requiring VA-ECMO compared with individuals without VA-ECMO before heart transplantation. Six hours of exposure to VA-ECMO also decreased left ventricular levels of cardiolipin and tafazzin in healthy swine compared with sham controls. To explore whether cardiolipin depletion by VA-ECMO increases infarct size, we performed left anterior descending artery occlusion for a total of 120 minutes followed by 180 minutes of reperfusion in adult swine in the presence and absence of MTP-131, an amphipathic molecule that interacts with cardiolipin to stabilize the inner mitochondrial membrane. Compared with reperfusion alone, VA-ECMO activation beginning after 90 minutes of left anterior descending artery occlusion increased infarct size (36±8% versus 48±7%; P<0.001). VA-ECMO also decreased cardiolipin and tafazzin levels, disrupted mitochondrial integrity, reduced electron transport chain function, and promoted oxidative stress. Compared with reperfusion alone or VA-ECMO before reperfusion, delivery of MTP-131 before VA-ECMO activation reduced infarct size (22±8%; P=0.03 versus reperfusion alone and P<0.001 versus VA-ECMO alone). MTP-131 restored cardiolipin and tafazzin levels, stabilized mitochondrial function, and reduced oxidative stress in the left ventricle. We identified a novel mechanism by which VA-ECMO promotes myocardial injury and further identify cardiolipin as an important target of therapy to reduce infarct size and to preserve mitochondrial function in the setting of VA-ECMO for acute myocardial infarction.

Abstract GS.08: Cardiolipin Is A Novel Target Of Therapy To Mitigate Myocardial Injury Due To Veno-arterial Extracorporeal Membrane Oxygenation (va-ecmo)

Cardiolipin (CL) is a mitochondrial specific phospholipid that maintains integrity of the electron transport chain (ETC) and plays a central role in myocardial ischemia-reperfusion injury. VA-ECMO use to provide hemodynamic support for acute myocardial infarction (AMI) has grown exponentially; is associated with poor outcomes; and is the subject of active clinical trials, yet the mechanistic impact of VA-ECMO on myocardial damage in AMI remains poorly understood. We hypothesized that VA-ECMO acutely depletes myocardial CL and promotes myocardial damage in AMI. We first report that levels of CL and tafazzin, a key enzyme required for CL synthesis, are significantly reduced in the left ventricles (LV) of human subjects requiring VA-ECMO compared to subjects without VA-ECMO prior to heart transplantation. Six hours of exposure to VA-ECMO also decreased LV levels of CL and tafazzin in healthy swine compared to sham controls. To explore whether CL depletion by VA-ECMO increases infarct size, we performed left anterior descending artery (LAD) occlusion for a total of 120 minutes followed by 180 minutes of reperfusion in adult swine in the presence and absence of MTP-131, an amphipathic molecule that interacts with CL to stabilize the inner mitochondrial membrane. Compared to reperfusion alone, VA-ECMO activation beginning after 90 minutes of LAD occlusion increased infarct size (33±11% vs 48±7%, p&lt;0.001). VA-ECMO also decreased CL and tafazzin levels, disrupted mitochondrial structural integrity, reduced ETC function and promoted oxidative stress. Compared to reperfusion alone or VA-ECMO before reperfusion, intracoronary delivery of MTP-131 five minutes before VA-ECMO activation reduced infarct size (22±8%, p=0.03 vs IRI and p&lt;0.001 vs VA-ECMO). Treatment with MTP-131 also restored CL and tafazzin levels, stabilized mitochondrial function, and reduced oxidative stress in the LV. Our results identify a novel mechanism by which VA-ECMO promotes myocardial dysfunction and further identify cardiolipin as an important target of therapy to reduce infarct size and preserve mitochondrial function for patients requiring VA-ECMO for acute myocardial infarction. Future clinical studies are required to test the translational utility of this approach.

Ginsenoside Rh2 mitigates myocardial damage in acute myocardial infarction by regulating pyroptosis of cardiomyocytes

ABSTRACT Background Acute myocardial infarction (AMI) is one of the most important causes of mortality among patients with cardiovascular disease. Ginsenoside Rh2 plays a protective role in cardiovascular diseases. Furthermore, pyroptosis reportedly participates in regulating the occurrence and development of AMI. However, whether ginsenoside Rh2 contributes to mitigating AMI by regulating cardiomyocyte pyroptosis remains unknown. Methods In the present study, we established an AMI model in rats. Next, we determined the effects of ginsenoside Rh2 on AMI by examining the myocardial infarct area, while regulation of myocardial pyroptosis was determined by assessing related factors. We established a cardiomyocyte model using hypoxia/reoxygenation (H/R) treatment. The expression of pyroptosis-related factors was determined following ginsenoside Rh2 treatment. In addition, we evaluated the correlation between ginsenoside Rh2 and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway at the mechanistic level. Results Herein, we observed that ginsenoside Rh2 alleviated AMI in rats and cells. Notably, the expression levels of inflammatory factors were reduced in AMI rats and cells. Furthermore, AMI rats and cells exhibited high expression levels of cleaved caspase-1 and gasdermin D, which were downregulated following treatment with ginsenoside Rh2. Further analysis revealed that ginsenoside Rh2 could inhibit cardiomyocyte pyroptosis by regulating the PI3K/AKT signaling pathway. Conclusions Collectively, the findings of the present study demonstrated that ginsenoside Rh2 regulates pyroptosis in cardiomyocytes to alleviate AMI in vivo and in vitro, thereby affording a novel therapeutic approach to treat AMI.

Transvalvular Unloading Mitigates Ventricular Injury Due to Venoarterial Extracorporeal Membrane Oxygenation in Acute Myocardial Infarction

Whether extracorporeal membrane oxygenation (ECMO) with Impella, known as EC-Pella, limits cardiac damage in acute myocardial infarction remains unknown. The authors now report that the combination of transvalvular unloading and ECMO (EC-Pella) initiated before reperfusion reduced infarct size compared with ECMO alone before reperfusion in a preclinical model of acute myocardial infarction. EC-Pella also reduced left ventricular pressure-volume area when transvalvular unloading was applied before, not after, activation of ECMO. The authors further observed that EC-Pella increased cardioprotective signaling but failed to rescue mitochondrial dysfunction compared with ECMO alone. These findings suggest that ECMO can increase infarct size in acute myocardial infarction and that EC-Pella can mitigate this effect but also suggest that left ventricular unloading and myocardial salvage may be uncoupled in the presence of ECMO in acute myocardial infarction. These observations implicate mechanisms beyond hemodynamic load as part of the injury cascade associated with ECMO in acute myocardial infarction.

Relationship between the degree of myocardial damage according to contrast-enhanced cardiac magnetic resonance imaging and laboratory data in patients with acute myocardial infarction

Aim. To evaluate the information value of a complex of clinical and biochemical parameters of myocardial damage in predicting the development of transmural myocardial damage according to magnetic resonance imaging (MRI) in patients with acute myocardial infarction (AMI).Material and methods. The study included patients admitted to the emergency cardiology department with acute coronary syndrome. All patients underwent invasive coronary angiography, laboratory tests, and dynamic determination of cardiac biomarkers. In the interval of 6,1±4 days from admission to the hospital, patients underwent contrast-enhanced cardiac MRI. According to the pattern of delayed contrast enhancement, patients were divided into two groups: with a transmural and subendocardial pattern.Results. The mean age of patients was 62,5±10,5 years, while 27 (71,1%) had ST-segment elevation AMI. Among the risk factors for coronary artery disease, dyslipidemia (89,5%), hypertension (68,4%), and smoking (57,9%) were the most common. Creatine phosphokinase-MB (CPK-MB), serum high-sensitivity cardiac troponin I (cTnI) and C-reactive protein (CRP) values after 24 h were significantly higher in patients with transmural hyperenhancement. Moderate positive relationship was found between the global size of left ventricular (LV) damage according to MRI data and the levels of CPK-MB after 24 h and 4 days, as well as with CRP after 24 h, 4 and 7 days, and cTnI level after 24 h and 4 days. In the group of patients with transmural pattern, the global size of LV damage was significantly higher. Patients of this group were characterized by higher prevalence of microvascular obstruction. In a univariate regression analysis, there were following significant predictors of transmural myocardial damage: CPK-MB after 4 days (p=0,023) and ST segment elevation (p=0,029). Multivariate regression analysis showed that the only independent predictor of transmural myocardial damage was an increase in CPKMB after 4 days (p=0,023).Conclusion. An independent predictor of LV transmural damage in AMI was an elevated level of CPK-MB after 4 days. However, this laboratory marker had unsatisfactory information completeness and predictive quality. In this regard, cardiac MRI in patients with AMI, compared with the standard clinical assessment, can be considered preferable for assessing the depth of myocardial damage, risk stratification, and prognosis.

Cardiac External Counterpulsation Attenuates Myocardial Injury by Regulating NRF2-mediated Ferroptosisin and Oxidative stress Injury.

Objectives To explore the role of the external counterpulsation (ECP) myocardial injury by controlling NRF2-mediated ferroptosis and oxidative stress damage in acute myocardial infarction. Methods Twenty acute myocardial infarction (AMI) participants hospitalized from January 2021 to January 2022 were enrolled. In addition, 20 healthy individuals who had a physical examination at our hospital served as normal controls. Before the AMI patients were given ECP therapy, the blood samples were collected and echocardiography was performed as the data of AMI cohort. Then, the blood samples were collected and echocardiography was performed following the ECP therapy as the data of AMI + ECP cohort. The heart function was assessed by echocardiography test. Results Our findings demonstrated that ECP could reduce heart damage in patients with AMI. In the current study, we found that ECP could reduce heart damage in patients with AMI through increasing the LV-EF% and enhancing LVEDV and LVESV, and the difference was statistically significant (P < 0.05). ECP could reduce the levels of oxidative stress and ferroptosis markers in blood samples of AMI patients, which was through the upregulation of NRF2 and HO-1 expression, and the difference was statistically significant (P < 0.05). Taken together, all data implied that ECP was able to attenuate myocardial injury by regulating NRF2-mediated ferroptosis and oxidative stress in AMI patients, and the difference was statistically significant (P < 0.05). Conclusion Our findings in this research are that cardiac ECP is able to attenuate myocardial injury by regulating NRF2-mediated ferroptosis and oxidative stress injury in AMI patients. This certainly gives the possibility of a clinically effective treatment for AMI patients, although further clinical trials need to be validated.

Simultaneous detection of acute myocardial infarction -related miR-199a and miR-499 based on a dual-emission CdTe fluorescent probe and T7 exonuclease-assisted signal amplification

The early diagnosis of acute myocardial infarction (AMI) was a tough nut in both clinical medicine and forensic science since the occurrence of gross changes needed at least 12 h. Compared to other diagnostic methods, microRNA was reported as an earlier cardiac biomarker with higher sensitive. In this work, we designed a novel fluorescent analytical strategy using a dual-emission probe based on T7 Exo-assisted target recycling amplification for simultaneous detection of AMI-related miR-199a and miR-499, which could indicate myocardial ischemia or damage in AMI. The dual-emission probe was conducted by yellow-emission and red-emission CdTe quantum dots capped with beta-cyclodextrin. The florescence of probe was firstly quenched by graphene oxide (GO) and then recovered in the presence of target miR-199a and miR-499. Under the optimized conditions, the limit of detection as low as 0.1 pM was obtained and the overall test could be performed within 50 min. Besides, the simultaneous detections of microRNAs in spiked serum samples were achieved with the recovery of 81.3–109.6%, which suggested the potential method for diagnosis in practical. The advantages of this method include easy operation, high accuracy and low labor cost, which makes point-of-care test possible both in hospital and forensic application.

Mitofilin Mitigates Myocardial Damage in Acute Myocardial Infarction by Regulating Pyroptosis of Cardiomyocytes.

BackgroundAcute myocardial infarction (AMI) can lead to sudden cardiac death after prolonged ischemia or heart failure (HF) and impaired left ventricular pump function. However, the underlying mechanism remains largely unknown. The purpose of this study was to investigate the role of mitofilin in alleviating AMI.MethodsRecombinant adenoviral vectors for mitofilin overexpression or mitofilin knockdown were constructed, respectively. A mouse AMI model was established and the effect of mitofilin on myocardial pyroptosis was examined by detecting the lactate dehydrogenase (LDH) level and inflammatory factors. Moreover, a cellular model of AMI was established by treating cardiomyocytes with hypoxia/reoxygenation (H/R). An enzyme-linked immunosorbent assay (ELISA) and a western blot analysis were used to detect the effect of mitofilin knockdown on the expression of pyroptosis-related factors. Furthermore, the regulatory role of mitofilin in PI3K/AKT pathway was evaluated by the western blot and PI3K inhibitor.ResultsMitofilin was downregulated in the heart tissue of the AMI mice and H/R induced cardiomyocytes. The overexpression of mitofilin significantly alleviated AMI and reduced pyroptosis-related factors. Meanwhile, in cardiomyocytes, mitofilin knockdown aggravated cellular damages by promoting pyroptosis. Further analysis showed that the anti-pyroptotic effect of mitofilin was dependent on the activation of the PI3K/AKT signaling pathway.ConclusionsOur study suggests that mitofilin regulates pyroptosis through the PI3K/AKT signaling pathway in cardiomyocytes to ameliorate AMI, which may serve as a therapeutic strategy for the management of AMI.

The prevalence of ischemic pattern of heart damage in patients with acute myocardial infarction depending on the presence of obstructive coronary artery disease: Magnetic resonance study

Currently, there are practically no works that are devoted to the analysis of different types of damage to ischemic and nonischemic patterns in patients with acute myocardial infarction (AMI), depending on the nature of atherosclerotic lesions of the coronary arteries.In this regard, the aim of this work was to evaluate the frequency of ischemic pattern of heart damage in patients with AMI depending on the presence of obstructive coronary artery disease.Material and Methods. The study retrospectively included patients with a working diagnosis of acute coronary syndrome (ACS) who underwent contrast-enhanced cardiac magnetic resonance (MR) imaging (CMR) during the first week after hospitalization. A 1.5 T CMR was performed using a standard protocol. T2-WI, T1-WI, and IR-images were visually assessed for edema and scar/necrosis, respectively. The pattern of acute ischemic damage to the left ventricular (LV) myocardium was an increase in the signal intensity on T2-WI as a sign of myocardial edema and late gadolinium enhancement (LGE) with a typical ischemic nature of contrast enhancement: subendocardial/subtransmural/transmural. The non-ischemic nature of myocardial injury was defined as intramyocardial/subepicardial LGE.Results. Based on invasive coronary angiography (ICA) data, patients were divided into two groups: group of myocardial infarction (MI) and coronary artery disease (MICAD group) and group of MI and non-obstructive coronary arteries (MINOCA group). It was found that the frequencies of occurrence of subendocardial pattern of cardiac LGE in early CMR did not differ in the groups of AMI patients against the background of obstructive and non-obstructive coronary artery disease (CAD). The most characteristic MR-pattern in MICAD patients was transmural LGE, including that in combination with microvascular obstruction (MVO). The most characteristic MR-pattern in MINOCA patients was mid-wall/insertion point LGE. Subepicardial LGE occurred with equal frequency in MICAD and MINOCA patients.Conclusion. The most pathognomonic MR-pattern of myocardial damage in AMI against the background of obstructive CAD was the transmural type of LGE with or without the phenomenon of MVO. Identification of the subendocardial type of LGE in patients with MINOCA allowed to stratify these patients into a higher risk group with a further change in treatment tactics.

Inhibition of the lncRNA DANCR attenuates cardiomyocyte injury induced by oxygen-glucose deprivation via the miR-19a-3p/MAPK1 axis.

Long noncoding RNAs (lncRNAs) have been considered as crucial regulators of acute myocardial infarction (AMI). In this study, to analyze the effect of differentiation antagonizing nonprotein coding RNA (DANCR) of lncRNA on cardiomyocyte damage in AMI, cardiomyocyte injury was induced by oxygen-glucose deprivation (OGD). Cell counting kit-8 (CCK-8) assay and flow cytometry were used to assess cell viability and apoptosis, respectively. Quantitative real-time PCR was used to measure the expression levels of DANCR and miR-19a-3p. Bioinformatics analysis and luciferase gene reporter assay were utilized to explore the relationship among DANCR, miR-19a-3p, and mitogen-activated protein kinase 1 (MAPK1). CCK-8 and TUNEL assays were used to explore the effects of DANCR alone or plus miR-19a-3p on the viability and apoptosis of OGD/R-exposed HL-1 cells. Western blot analysis was used to detect changes in the MAPK1/ERK1/2 pathway in HL-1 cells. We found that DANCR expression and miR-19a-3p level are negatively correlated as DANCR expression is increased, while miR-19a-3p level is decreased in AMI patients' serum and OGD/R-exposed HL-1 cells. DANCR knockdown increased miR-19a-3p level, and miR-19a-3p inhibition increased DANCR expression. Moreover, DANCR directly binds to miR-19a-3p. DANCR knockdown reduced viability but induced apoptosis in OGD/R-exposed HL-1 cells, while miR-19a-3p inhibition weakens these effects. Furthermore, MAPK1 is a target of miR-19a-3p. miR-19a-3p overexpression decreases MAPK1 and ERK1/2 in HL-1 cells, while miR-19a-3p inhibition increases MAPK1 and ERK1/2 in HL-1 cells. Moreover, DANCR knockdown reduces myocardium apoptosis in mice with the left anterior descending artery ligated. DANCR knockdown effectively restores myocardial cell apoptosis by regulating the miR-19a-3p/MAPK1/ERK1/2 axis.

C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study

Background: C-reactive protein (CRP) is a well-known marker of inflammation. It is less known that CRP mediates tissue damage in acute myocardial infarction (AMI) thus potentially worsening prognosis. A newly developed specific CRP adsorber allows efficient lowering of CRP levels and may improve survival.Objectives: Aim of this multi-center, controlled, non-randomized first-in-man CRP apheresis in Acute Myocardial Infarction study (CAMI-1) was to investigate the relationship between CRP levels (CRP gradient), myocardial infarct size and function as well as safety and efficacy of CRP apheresis in the setting of acute ST-segment Elevation Myocardial Infarction (STEMI) in humans.Methods: Eighty-three patients (45 apheresis, 38 controls) were recruited. CRP apheresis was performed 24 ± 12, 48 ± 12, and optionally 72 ± 12 h after onset of symptoms. First aphereses were performed at a median CRP concentration of 23.0 mg/L (range 9–279). In each apheresis session, 5,900 ± 400 mL plasma was processed via peripheral venous access. Primary study endpoint was a reduction in myocardial infarct size after STEMI as determined by cardiovascular magnetic resonance (CMR).Results: In controls, the CRP concentration significantly correlated with infarct size (p = 0.002) and decreased myocardial function (p ≤ 0.001). The CRP concentration in apheresis patients did not correlate with infarct size (p = 0.66) or left ventricular (LV) function (p = 0.79) and global strains and therefore significantly differed from controls (p = 0.03 and p = 0.002). Three major adverse cardiac events occurred in the control group after 12 months, none occurred in the apheresis group. Mean CRP depletion achieved over all apheresis procedures was 53.0 ± 15.1%. Apheresis sessions were well-tolerated. Reduced infarct size in the apheresis group compared to the control group (primary endpoint) was not achieved according to the original statistical analysis plan. Taking into account the individual CRP levels, however, revealed significant results. Modifications of the analysis plan were introduced in order to recruit a sufficient number of patients.Conclusions: This pilot study in humans reveals a correlation between CRP concentration and myocardial infarct size. CRP concentrations in STEMI can effectively be reduced by CRP apheresis without relevant side effects. CRP apheresis has the potential to interfere with deleterious aspects of STEMI. By lowering CRP levels, it resulted in the loss of correlation of CRP concentrations with myocardial infarct sizes as well as LV function. These results encourage a larger, randomized clinical trial.Clinical Trial Registration: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008988, DRKS00008988.

Ginsenoside Rb1 Inhibits Cardiomyocyte Autophagy via PI3K/Akt/mTOR Signaling Pathway and Reduces Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion injury (MIRI) is the major cause of myocardial cell damage in acute myocardial infarction, and its treatment remains a clinical challenge. Ginsenoside Rb1 showed protective effects on the cardiovascular system; however, the underlying mechanism remains largely unclear. Effects of Ginsenoside Rb1 on rat MIRI-induced myocardial infarct size were evaluated through TTC staining. TUNEL assay and flow cytometry analysis were employed to estimate cell apoptosis. Apoptosis, autophagy and PI3K/Akt/mTOR pathway-related proteins were estimated via western blot. Expression of Beclin1 in myocardial tissues were examined by immunohistochemical analysis. Expression levels of IL-1[Formula: see text], TNF-[Formula: see text] and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA). Here, we found that Ginsenoside Rb1 treatment not only alleviated MIRI in rats but also protected H9C2 cells against hypoxia/reoxygenation induced damage. Ginsenoside Rb1 abolished the MIRI-induced activation of autophagy. Meanwhile, we found that treatment of 3-MA (autophagy inhibitor) could enhance the protective effects of Ginsenoside Rb1 on H9C2 cells during H/R. Moreover, Ginsenoside Rb1 treatment resulted in the activation of the PI3K/Akt/mTOR pathway, and treatment of LY294002 (PI3K/Akt pathway repressor) abolished the protective effects of Ginsenoside Rb1 on myocardial in vitro and in vivo. Our results suggest that Ginsenoside Rb1 functions as a protector against MIRI by repressing cardiomyocyte autophagy through the PI3K/Akt/mTOR signaling pathway.

Human umbilical cord mesenchymal stem cells-derived exosomes transfers microRNA-19a to protect cardiomyocytes from acute myocardial infarction by targeting SOX6

ABSTRACTExosomes secreted by human umbilical cord mesenchymal stem cells (hucMSCs) protect cardiomyocytes from anoxia-reoxygenation injury. But the mechanism of hucMSC-exo-microRNA (miR)-19a in acute myocardial infarction (AMI) remains unclear. For this study, cardiac function related indicators, inflammatory factors and markers of myocardial injury, cardiomyocyte injury, infarct size, and apoptosis were detected in vivo experiments. The gain-and loss-of function was performed to evaluate the effects of hucMSC-exo with down/upregulated miR-19a on AMI rats and hypoxic H9C2 cells. Western blot analysis was used to detect levels of AKT/JNK3/caspase-3 axis-related proteins. Consequently, hucMSC-exo alleviated AMI and inhibited cardiomyocyte apoptosis. miR-19a was downregulated in AMI tissues and cells, and increased after hucMSC-exo treatment. miR-19a knockdown in hucMSC-exo impaired the protective role of hucMSC-exo alone in the AMI damage. SOX6 is a target gene of miR-19a and its inhibition lightened hypoxic damage of H9C2 cells. SOX6 knockdown together with miR-19a inhibition in hucMSC-exo activated AKT and inhibited JNK3/caspase-3 axis. Taken together, hucMSC-exo protected cardiomyocytes from AMI injury by transferring miR-19a, targeting SOX6, activating AKT, and inhibiting JNK3/caspase-3 activation. This study may provide new understanding for AMI treatment.

PentraSorb C-Reactive Protein: Characterization of the Selective C-Reactive Protein Adsorber Resin.

C-reactive protein (CRP) is well known as a general marker of inflammation. It furthermore represents a reliable risk factor for cardiac events and mediates tissue damage in acute myocardial infarction (AMI). It has been demonstrated that selective CRP depletion by extracorporeal apheresis in a porcine AMI model had beneficial effects on the infarcted area and the cardiac output. We therefore developed a novel adsorber for CRP apheresis from human plasma (PentraSorb CRP). It is intended for use in the clinic as therapy for patients suffering from AMI or other acute inflammatory diseases with elevated CRP plasma levels. The PentraSorb resin specifically bound CRP from human blood plasma and almost no other proteins as determined via Sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE). The resin further efficiently and selectively depleted CRP from plasma with low as well as high CRP concentrations (10-100 mg/L) at different flow rates, ranging from 17 to 40 mL/min. The resin was regenerable for up to 200 times without losing its CRP binding capacity or affecting biocompatibility. The depletion of CRP from plasma was comparable between the utilized small-scale column (0.5 mL resin) and the PentraSorb CRP adsorber (20 mL resin volume). The established features can therefore be applied to the clinical setting. In summary, PentraSorb CRP provides a novel, specific, and efficient CRP-binding resin that could be used in apheresis therapy for patients suffering from inflammatory diseases such as AMI, stroke, acute pancreatitis, and Crohn's disease.

Evaluation of Adjuvant Biomarkers in Acute Myocardial Infarction

Background: Acute myocardial infarction (AMI) is one of the dreadful complications of cardiovascular disease causing increasing mortality worldwide. The alterations (increase or decrease) of intracellular and extracellular enzymes or components in developing phase of disease are called markers. Variations in biochemical markers like Cardiac Troponins - T (ctnl) creatine kinase may correlate with the extent of myocardial damage in Acute myocardial infarction (AMI). &#x0D; Aim and Objectives: This study was undertaken to evaluate serum sodium, potassium, urea and creatinine as adjunctive parameters along with cardiac markers, which probably help in better prognosis of AMI. &#x0D; Material Methods: 100 subjects were included in this study with confirmed diagnosis of recent AMI by the physicians and 100 healthy persons visiting hospital for routine checkup. Blood samples of both group were analyzed for serum urea by Diacetylmonoxime, creatinine by Jaffe's, &amp;sodium &amp; potassium by flamephotometry uing Bio- Lab Diagnostic Kit Methods. Whereas cardiac troponin - T was done by chemiluminescence immunoassay (CLIA) on Lumax hormone analyser and CKMB by kinetic kit method.&#x0D; Results: There were statistically significant decreased levels of serum sodium (P&lt;0.0001) potassium (p&lt;0.0001), and elevated levels of urea (p&lt;0.0001) and creatinine (0.0001) observed in AMI. Both established cardiac markers Trop- T and CKMB were extremely statistically significantly increased (p&lt;0.0001) as compared to control group.&#x0D; Conclusion: This study showed association of routine blood tests such as urea, creatinine, sodiumand potassium hence can be used as supplement information with regard to treatment and better prognosis of AMI patients or these could be cost effective time saving adjuvant markers in management of myocardial infarction.

The role of prognostic assessment with biomarkers in chronic kidney disease: a narrative review

Chronic kidney disease (CKD) is associated with high morbidity and mortality. In the past, residual kidney function in CKD patients was assessed by serum creatinine-based equations. However, due to low accuracy of those calculations there is a need for alternative biomarkers. As cardiovascular disease is a major cause of increased mortality in patients with CKD novel biomarkers to estimate risk of cardiovascular death are vital. We reviewed articles approaching beta-trace protein, beta-2 microglobulin (B2MG) and cystatin C as alternative biomarkers to estimate glomerular filtration rate (GFR) in CKD patients. Furthermore, we included recent publications showing the role of high sensitive troponin and sFlt-1 in assessment of progressing cardiovascular disease in patients with renal failure as well as the role of inflammatory biomarkers in those patients. Lastly, we present basic research regarding the role of APOL1 gene variants, suPAR and αvβ3 integrin on decline of renal function. Measuring GFR with serum creatinine and cystatin C seems to be more accurate than equations based on beta-trace protein and B2MG. Beta-trace protein however, seems to be a predictive marker to assess risk of end-stage renal disease. A recent study showed that serum sFlt-1 levels after heparin injection could predict cardiovascular mortality in patients with chronic renal failure. High sensitive troponin is a recently introduced biomarker measuring myocardial damage in acute myocardial infarction (MI) and can predict short-term all cause death in patients with reduced GFR. Progression of renal disease is attributed to increased inflammation levels and can be predicted by measuring proinflammatory biomarkers such as TNF-receptor 1, TNF-receptor 2 and KIM-1. We gave an updated review of novel biomarkers in CKD. While some have proven useful in certain situations it is unclear whether one single biomarker for assessing renal function or predicting mortality in patients with renal failure can be found.

Platelet microparticle number is associated with the extent of myocardial damage in acute myocardial infarction.

IntroductionActivated platelets generate microparticles. Increased platelet microparticles occur in acute myocardial infarction (AMI) and contribute to intracoronary thrombosis and subsequent myocardial injury. This study aimed to investigate the impact of platelet microparticles on intracoronary thrombosis by assessing the relationship between platelet microparticles and the extent of myocardial damage in AMI.Material and methodsThis was a cross sectional study. The subjects were patients with acute coronary syndrome (ACS). Forty-one consecutive subjects with ACS admitted to intensive cardiovascular care unit were enrolled. The clinical spectrum of ACS comprised AMI (n = 26), both ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI), and unstable angina (n = 15). Platelet microparticles were isolated from peripheral venous blood and detected with anti-CD42b-PE by the flow cytometry method. The extent of myocardial damage was determined by measuring the peak level of serial cardiac enzymes within 24 h of admission.ResultsSubjects with AMI had a significantly higher number of platelet microparticles than those with unstable angina (4855 ±4509/µl vs. 2181 ±1923/µl respectively; p = 0.036). Subjects with STEMI had the highest number of platelet microparticles, but no significant difference was detected as compared to those with NSTEMI (5775 ±5680/µl vs. 3601 ±1632/µl). The number of platelet microparticles in AMI was positively associated with the extent of myocardial damage (peak CK-MB: r = 0.408, p = 0.019 and peak GOT: r = 0.384, p = 0.026).ConclusionsThe number of platelet microparticles was increased in AMI as compared to unstable angina and associated with the extent of myocardial damage.

Secretory Phospholipase A2 Tipe II (SPLA II) In Cardiovascular Disease

Inflammatory reactions contribute to the pathogenesis of cardiovascular conditions such as atherosclerosis and ischemic damage in acute myocardial infarction (AMI). Among the mediators involved in inflammation are secretory phospholipase A2 group II (sPLA2-II) enzymes. Though some cells constitutively express Spla2-II, the synthesis by cells such as hepatocytes is typical for an acute-phase reactant. Recent literature suggest multiple roles for sPLA2-II in cardiovascular disease. In this review we discuss the role of sPLA2-II in included that sPLA2-II appears to be an inportant inflammatory mediator of cardiovascular disease.

Abstract 16525: Left Ventricular Unloading Before, Not After, Reperfusion Limits Infarct Size and Improves Survival in Acute Myocardial Infarction: A Bench to Bedside Study

Ischemia-reperfusion injury (IRI) is a major determinant of myocardial damage in acute myocardial infarction (AMI). We explored the hypothesis that reducing left ventricular wall stress (LV unloading) with an axial flow catheter (Impella) before, not after, coronary reperfusion reduces infarct size and improves survival. Methods: We first employed a model of AMI. After 90 minutes of LAD occlusion, adult, male swine (n=4/group) were randomized to: 1) 120 minutes of reperfusion alone (IRI), 2) 30 minutes of LV unloading before 120 minutes of reperfusion (Impella to Balloon Group; ITB) or 3) 30 minutes of reperfusion followed by LV unloading and an additional 120 minutes of reperfusion (Balloon to Impella Group; BTI). Infarct size, myocardial kinase activity, and mitochondrial integrity were quantified. To explore the clinical utility of LV unloading before reperfusion we retrospectively studied all patients in the USPella registry presenting with ST-segmentc elevation AMI and cardiogenic shock who received an Impella within 120 minutes before (n=41; STEMI-ITB) or within 120 minutes after (n=76; STEMI-BTI) percutaneous reperfusion between 2009 and 2014. Results: Compared to IRI alone, infarct size was reduced in the ITB group, not the BTI group (62±2% vs 33±6% vs 58±15%, IRI vs ITB vs BTI, p&lt;0.01 for IRI vs ITB; p&lt;0.05 for ITB vs BTI). Levels of phosphorylated Akt, Erk-1/2, and GSK3b were increased within the infarct zone in the ITB, not BTI group. Mitochondrial numbers and markers of integrity were higher within the infarct zone in the ITB, compared to IRI or BTI. In the registry, in-hospital (51% vs 28%, p=0.02) and 30-day survival (42% vs 20%, p=0.03) were higher in the STEMI-ITB than the STEMI-BTI group. A STEMI-ITB time of less than 60 minutes (n=38) was associated with higher in-hospital survival than a STEMI-BTI time of less than 60 minutes (n=40) (50% vs 25%, p=0.02). Conclusion: Primary LV unloading before, not after, coronary reperfusion reduces infarct size, increases cardioprotective signaling, and improves mitochondrial integrity. These findings are supported by improved survival among patients treated with an Impella before, not after reperfusion in AMI. Future studies are required to explore the clinical utility of primary LV unloading in AMI.

Mechanical Pre-Conditioning With Acute Circulatory Support Before Reperfusion Limits Infarct Size in Acute Myocardial Infarction

ObjectivesThis study tested the hypothesis that first reducing myocardial work by unloading the left ventricle (LV) with a novel intracorporeal axial flow catheter while delaying coronary reperfusion activates a myocardial protection program and reduces infarct size. BackgroundIschemic heart disease is a major cause of morbidity and mortality worldwide. Primary myocardial reperfusion remains the gold standard for the treatment of an acute myocardial infarction (AMI); however, ischemia–reperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1α is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3β. MethodsAMI was induced by occlusion of the left anterior descending artery (LAD) via angioplasty for 90 min in 50-kg male Yorkshire swine (n = 5/group). In the primary reperfusion (1° Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1° Unloading) group, after 90 min of ischemia the axial flow pump was activated and the LAD left occluded for an additional 60 min, followed by 120 min of reperfusion. Myocardial infarct size and kinase activity were quantified. ResultsCompared with 1° Reperfusion, 1° Unloading reduced LV wall stress and increased myocardial levels of SDF-1α, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase-3β in the infarct zone. 1° Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1° Reperfusion (73 ± 13% vs. 42 ± 8%; p = 0.005). Myocardial levels of SDF-1 correlated inversely with infarct size (R = 0.89; p < 0.01). ConclusionsCompared with the contemporary strategy of primary reperfusion, mechanically conditioning the myocardium using a novel axial flow catheter while delaying coronary reperfusion decreases LV wall stress and activates a myocardial protection program that up-regulates SDF-1α/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI.